Policy and Medicine

American Medical Association: Launches Improving Health Outcomes Initiative

To bolster ongoing efforts to address the leading causes of suffering and death in our nation and to engage the physician community in improving national health outcomes, the American Medical Association (AMA) recently announced the first phase of its new multi-year, multi-million dollar improving health outcomes (IHO) initiative: preventing cardiovascular disease and type 2 diabetes and improving health outcomes for those with these conditions. 

“Cardiovascular disease accounts for one-third of all deaths in our nation, and one-in-three adults could have diabetes by 2050 if current trends continue,” said AMA President Jeremy Lazarus, M.D. “The toll of these diseases on our nation is staggering – in terms of human suffering and health care costs. T he direct and indirect cost of cardiovascular disease and diabetes is more than $535 billion a year.” 

The AMA’s efforts will include working closely with ongoing national programs, galvanizing America’s physicians and patients to focus on preventing and controlling cardiovascular disease and diabetes and teaming with new partners to address high blood pressure and prediabetes. 

“When America’s physicians work together with patients, communities and other members of the health care team we can have a tremendous impact on health outcomes,” said Dr. Lazarus at the National Summit on Health Disparities hosted by the National Minority Quality Forum.  “We will begin our new initiative with a focus on risk factors for cardiovascular disease and diabetes, aiming for optimal blood pressure, blood sugar and cholesterol levels for all U.S. adults.” 

The AMA chose the National Summit on Health Disparities to launch its effort as rates of diabetes are higher in Native American, African American and Latino communities, and African Americans are more likely to have cardiovascular disease.  

Cardiovascular Disease 

The key to preventing cardiovascular disease is preventing and treating high blood pressure.  One-in-three U.S. adults has high blood pressure, the number one risk factor for disability and death.  The AMA is partnering with the Armstrong Institute for Patient Safety and Quality, a research institute within Johns Hopkins Medicine, to help meet and exceed the goal of the U.S. Department of Health and Human Services’ Million Hearts Initiative to bring the high blood pressure of 10 million more Americans under control by 2017.  

AMA and the Armstrong Institute will work with physicians, care teams, patients and communities to better understand the reasons for uncontrolled blood pressure, find clinically meaningful solutions and share lessons learned. 

Directed by Peter Pronovost, senior vice president for patient safety and quality at Johns Hopkins Medicine, the Armstrong Institute is best known for its successes in dramatically reducing central-line associated bloodstream infections in hospital ICUs. The Armstrong Institute is committed to eliminating preventable harm for patients, optimizing patient outcomes and experience and reducing waste in health care delivery. 

Diabetes 

One-in-three U.S. adults has prediabetes, a condition in which blood sugar is higher than normal but not yet in the diabetic range.  Those with prediabetes are at greatly increased risk of developing type 2 diabetes.  The AMA’s initial efforts to help prevent diabetes will be in support of the Centers for Disease Control and Prevention’s (CDC) National Diabetes Prevention Program.  The CDC encourages physicians to refer patients with prediabetes to an evidence-based lifestyle change program that helps increase physical activity, improve diet and achieve moderate weight loss, which reduces the risk for type 2 diabetes.  

In partnership with the YMCA of the USA, the AMA will work to increase physician referrals of patients with prediabetes to the evidence-based diabetes prevention programs offered by the YMCA. 

“We are excited to work with the AMA on our shared goal of preventing diabetes. Connecting physician practices to the YMCA’s Diabetes Prevention Program will ensure that those at greatest risk have the opportunity to prevent or delay diabetes,” said Jonathan Lever, vice president of health innovation and strategy, YMCA of the USA. “This novel collaboration between medical practices and community-based programs could prove to be a model for promoting health and wellness.”  

“These are the first steps toward the AMA’s ambitious, long-term goal of achieving measurable improvements in health outcomes for patients in the United States,” said Dr. Lazarus. “We look forward to partnering with many individuals and organizations who share these goals.” 

The IHO initiative is one of three parts of the AMA’s new five-year strategic plan, which includes improving patients’ health outcomes, accelerating change in medical education and enhancing practice sustainability and physician professional satisfaction – all critical factors in optimizing the health of our nation.

 

Simpson-Bowles and Daschle-Frist-Domenici: Unveil Plans for Reducing Healthcare Spending

In addition to the President’s FY 2014 we previously reported on, former Fiscal Commission heads, Alan Simpson and Erskine Bowles, unveiled an updated deficit reduction plan – building on a framework released in February 2013 – including $2.5 trillion in savings from spending cuts and revenue increases, of which $585 billion comes from healthcare reductions and reforms over the next 10 years.  Highlights from this plan, courtesy of Thorn Run Partners include: 

• Delivery System and Payment Reforms (-$60B/10): Among other recommendations, includes the cost of replacing the SGR with a payment freeze coupled with a short-term “modest” reduction below the freeze and medium-term development of a formula that promotes participation in new care models. Also expands penalties for avoidable complications and readmissions, as well as:  

o   Broadens competitive bidding to medical devices, laboratory tests, radiologic diagnostic services and other commodities;

o   Fosters “alternative benefit packages” (e.g., that combine Parts A, B and D and offer care coordination); and

• Ensures IPAB is not restricted by “special interest carve-outs.”  The report also recommends considering giving IPAB the prerogative to recommend benefit design and cost-sharing changes. 
• Reform Medicare Cost-Sharing Rules (-$90B/10): Proposes restricting Medigap first-dollar coverage and replacing current Medicare cost-sharing rules with a unified deductible, uniform co-insurance and out-of-pocket (OOP) maximum; the report also makes modifications to the original Fiscal Commission recommendation on cost-sharing changes, proposing varying the deductible and OOP limit with income. 
• Expand Income Relating of Medicare Premiums (-$65B/10) 
• Increase the Medicare Age with an Income-Related Buy-In (-$35B/10) 
• Reduce and Reform Post-Acute Care Payments (-$70B/10): Recommends adopting the President’s policy of reducing annual growth in payments to SNFs, IRFs, LTCHs and home health facilities.  
•   Reduce Various Payments to Hospitals (-$65B/10): Recommends a phase-out of all reimbursement for bad debts, reduced subsidies for graduate medical payments to “better align with patient care costs” and reduced enhanced payments to rural hospitals.     
• Reduce the Costs of Prescription Drugs in Medicare (-$90B/10): Recommends mandated rebates for dual eligibles covered under Part D but notes that “unlike other proposals, this recommendation would not extend rebates to new classes of beneficiaries who were not subject to rebates prior to implementation of Part D.” Bars pay-for-delay arrangements.
• Reduce Fraud, Abuse and Excessive Payments Within Medicare (-$25B/10): Among other policies, recommends giving HHS authority to align clinical lab payments with private-sector payments and reclassify certain payments for hospital outpatient evaluation/management (E/M) visits “so they are treated the same as similar visits to a physician’s office.” 
• Additional Recommendations: Relate to malpractice reform, a new waiver program for state innovation and reforming Medicaid financing by reducing overpayments to States. 

In addition, the Bipartisan Policy Center’s Health Care Cost Containment Initiative released a report (see executive summary) by former Sen. Majority Leaders Tom Daschle and Bill Frist, former Senate Budget Committee Chairman Pete Domenici, and former Congressional Budget Office Director Alice Rivlin presenting 50 health-specific recommendations estimated to reduce the federal deficit by $560B over 10 years. Highlights from this report, courtesy of Thorn Run Partners include: 

Medicare Networks: Creates a third option within FFS Medicare that beneficiaries could elect – or choose Traditional Medicare or a Medicare Advantage Plan – that would involve an ACO-like network. Beneficiaries electing these new Medicare Networks would receive incentives to enroll via discounted standard premiums, an opportunity to share in savings and differential cost-sharing for in-network and out-of-network providers. The SGR would be fixed, with the highest updates during a transition period going to physicians participating in Medicare Networks accepting 2-sided risk. 

Employer-Sponsored Health Insurance (ESI) Tax Exclusion: Replaces the ACA’s “Cadillac tax” on high-cost plans with a limit on the income tax exclusion for employer-sponsored health benefits at the dollar amount equal to the 80^th percentile of single and family (age and gender adjusted) ESI premiums in 2015 ($262B revenue increase/10).

Medicare Advantage (MA): Establishes a standardized minimum benefit for MA Plans that would include all services covered by traditional Medicare, a cost-sharing limit to protect against catastrophic expenses and slightly lower cost-sharing. Plans would be paid using a “competitive pricing system,” although this only would take effect in certain regions where it saves costs to the federal government versus the old benchmark (this proposal is detailed on p. 43 of the full report). Separately, the report recommends ending the MA Star Demonstration and “revert[ing] to the smaller bonus payments under current law.”

Modernized Benefit Design: Includes a single, combined A+B deductible and generally replaces co-insurance with co-payments on most covered services, similar to MedPAC recommendations, among several other provisions.  

• DME: Recommends continued implementation of competitive bidding but lower benchmarks for certain equipment types because “over the long term, we believe the median-bid level is unnecessarily generous to DME suppliers.” 
• Site of Care Differentials: Suggests equalizing the payment rates for E/M services to the rate of the lowest-cost setting, including facility payments (estimated to save $8.7B/10), and equalizing payments at the level of the lowest-cost site for procedures that are performed both in outpatient departments and physician offices in certain circumstances, such as when the procedure is conducted in physician offices more than half of the time (savings not estimated). 
• High-Quality, Low-Cost Drug Utilization: Makes various recommendations including:  

Adjusting the Part D LIS cost-sharing to encourage the use of high-value drugs (-$44.3B/10);

Changing Part B reimbursement for provider-administered drugs (specifically, changing the reimbursement to equal the average sales price of the medication plus a flat payment, with the flat payment being set separately – and being payment neutral, before any behavioral change – for each therapeutic class, as designated by HHS) (Savings not estimated);

Convert from Average Wholesale Price to Average Sales Price for remaining Part B drug and vaccine reimbursements (Savings not estimated);  

Address anti-competitive settlements between brand and generic drug manufacturers (-$4B/10); and

Close the REMS loophole that “inhibits development of generic drugs” (-$753M/10). 

• Graduate Medical Education: Makes several recommendations including reducing IME percentage add-on to inpatient hospital admissions from 5.5 percent to 3.5 percent and repurposing savings for performance-based incentive payments and additional residency slots.

AMSA Expanding Anti-Industry Scorecard to 400 Teaching Hospitals

We recently reported on a survey of 1,610 first- and third-year medical students and 739 residents regarding conflict of interest (COI) policies and their interactions with industry.  In our story, we noted that almost every year, the American Medical Students Association (AMSA) publishes a yearly “PharmFree Scorecard” that evaluates the COI policies at American medical schools.  Here is a little background and history on AMSA.

The PharmFree Scorecard is funded through the Consumer and Prescriber Education grant program, which resulted from the Neurontin settlement back in 2004.

It is because of organizations like PharmFree that frame all physician-industry collaboration as negative or unethical, that patients, physicians and biopharmaceutical professionals need a voice in the “conflict of interest mania,” such as the recently launched Partners for a Health Dialogue.  

Interestingly, while we cited to the 2012 results, AMSA just released its 2013 Scorecard, the sixth iteration of the scorecard.  The release comes as AMSA hosts its National PharmFree Week April 8-12, 2013.  The annual event “highlights the importance of putting patients first by addressing conflicts of interest and encouraging evidence rather than marketing-based education.”  Below is a summary of this year’s findings as well as additional information about AMSA activities. 

Interestingly, AMSA and Pew announced with this year’s data that they were also charged through a grant from the Oregon State Attorney General’s office to update the AMSA PharmFree Scorecard and expand it to 400 teaching hospitals.  Alongside Dr. Joseph Ross of Yale Medical School who served as a Methodology Consultant, AMSA and Pew developed the new AMSA PharmFree Scorecard set for release in 2014.  Given that payments to teaching hospitals must be reported under the Physician Payment Sunshine Act, the new scoring of teaching hospitals will bring increased scrutiny to physician-industry interactions at such hospitals.  

There will be two versions of the new Scorecard - one for medical schools and another for teaching hospitals.  The number of domains for the Scorecard has also expanded with 16 domains common to both versions and 2 additional domains for “Samples” and “Purchasing and Formulary Committees” specific to the teaching hospital version.  Other revisions to the Scorecard will include a new formula for assessing academic medical centers as well as revisions in the framework for grading schools.

 

2013 Findings

 

“Conflict of interest policies discourage inappropriate relationships and allow transparent and positive industry-physician collaborations to thrive,” said Daniel Carlat, director of the Pew Charitable Trusts’ prescription project, which supports AMSA’s work. “The 2013 scorecard shows medical schools are moving toward stronger conflict-of-interest standards.”

 

As of April 9, 2013, 153 out of 158 medical institutions considered eligible for grading have participated in the Scorecard, a 97% participation rate.  Of these 158 US medical schools, 40 receive “A”s (25%), 75 “B”s (47%), 14 “C”s (9%), and 13 “D”s (8%).  Thus, 115 of 158 medical schools (73%) now receive a grade of A or B for their COI policies, compared with 102 last year.  Approximately 8% of U.S. medical schools improved their COI policies since the 2011-2012 Scorecard.

 

Policies that apply only to medical students and/or residents, but not faculty, and (2) Policies that are only guidelines, without formal requirements, may only achieve a maximum grade of C.

 

13 schools (8%) receive a grade of F.  This includes 3 schools that submitted policies graded as F, two schools that stated they had no COI policy in place, and five schools that did not respond to repeated attempts at follow-up in 2008, 2009, 2010, 2011-12 and 2012-2013.  Three additional schools received an F as they did not submit new policies or demonstrate a continuing policy development process after remaining In Process for one year.  Three schools (2%) received a grade of In Process.  Here are some highlights from this year’s report:

 

• Roughly 80% of medical schools have perfect or close to perfect policies for on-campus CME.
• Only 4 medical schools – Univ. of South Dakota Sanford School of Medicine, Florida State Univ. College of Medicine, Stony Brook Univ. School of Medicine, and the Commonwealth Medical College -- completely ban sales representatives from campus.

• Only 41 schools (26%) have model policy in terms of disclosure, requiring personnel to disclose past and present financial ties with industry (e.g., consulting and speaking agreements, research grants) on a publicly-available website and disclosing these relationships to patients.
• All 8 of the Texas medical schools scored at least a B.  The University of Texas Medical Branch at Galveston, however, remains the lone A in the Lone Star state. All three of the Maryland medical schools scored at least a B, with both Johns Hopkins and University of Maryland Schools of Medicine receiving an A.
• Schools with model policies on speaking arrangements have grown tremendously; 44 schools ban or severely restrict participation in speaker bureaus.

 

Specifically, 18 schools have banned participation by their faculty on speakers’ bureaus: Harvard Medical School, NYU School of Medicine, Duke Univ. School of Medicine, Columbia Univ. College of Physicians and Surgeons, Univ. of Arkansas School of Medicine, Univ. of Maryland School of Medicine, Georgia Health Sciences Univ., Univ. of South Carolina School of Medicine, Univ. of Hawai’i John A Burns School of Medicine, Creighton Univ. School of Medicine, Wake Forest Univ. School of Medicine, Univ. of Massachusetts Medical School, Emory Univ. School of Medicine, Stanford Univ. School of Medicine, Albert Einstein College of Medicine, Univ. of Alabama Birmingham, Univ. of Florida and Jefferson Medical College.

 

The following is a list of domains and the number of perfect scores in each in 2013:

 

• 28 Schools have perfect scores for “On-campus continuing medical education;” improved from 20 in 2011-2, 15 in 2010, 3 in 2009 and 5 in 2008.  On-site education means within the medical school or hospital campus.  To gain a perfect score, “Industry is not permitted to provide direct financial support for educational activities, including CME, directly or through a subsidiary agency.  (However, companies may contribute unrestricted funds to a central fund or oversight body at the AMC, which, in turn, would pool and disburse funds for programs that are independent of any industry input or control.)”

 

• 98 medical schools have “Less stringent limitations to ensure independence of educational content (e.g., standards to establish freedom from industry influence of content, such as review and approval of presentations; language that prevents industry from selecting the speaker; a requirement that programs adhere to ACCME standards; or language such as: industry funding may be allocated for a particular topic, but must be provided directly to the department, not to individuals).  Despite trying to discredit the ACCME as a “non-governmental” organization, CMS recently recognized the critical importance of the ACCME Standards for Commercial Support in the final Sunshine Act rule, and non-compliance with such standards can result in loss of accreditation. 

 

• Off-campus continuing medical education –  102; improved from 88 in 2011-2, 75 in 2010, 49 in 2009 and 23 in 2008.  Off-site education is at outside facilities, including professional conferences.  AMSA measures this category based on how schools regulate compensation for travel or attendance at off-site lectures and meetings.  To gain a perfect score, “Personnel may not accept payment, gifts or financial support from industry to attend lectures and meetings. (An exception may be made for modest meals, if part of a larger program.)  Travel support may only be accepted if it is subject to institutional approval or industry is prevented from selecting (“earmarking”) the recipients.”  It is unclear, however, whether this category captures accredited CME or simply all off-campus educational events.

 

• Scholarships & Funds for Trainees – 123; improved from 108 in 2011-2, 94 in 2010, 66 in 2009 and 29 in 2008.  To gain a perfect score, “The policy must either prevent industry from earmarking or awarding funds to support the training of particular individuals (recipients must be chosen by the school or department), or the policy must mandate institutional review of the giving of funds. (This does not preclude grants that fund a specific research project.)”

 

• Gifts & Meals – 93; improved from 81 in 2011-2, 66 in 2010, 44 in 2009 and 19 in 2008.  To gain a perfect score in Gifts & meals, “All gifts and on-site meals funded by industry are prohibited, regardless of nature or value.”  Less stringent include limitations such as prohibitions above $50 per year, or gifts prohibited but meals allowed.

 

• Disclosure – 41; improved from 29 in 2011-2, 20 in 2010,  5 in 2009 and 1 in 2008.  To gain a perfect score, “Personnel are required to disclose past and present financial ties with industry (e.g., consulting and speaking agreements, research grants) on a publicly-available website and/or disclose such relationships to patients when such a relationship might represent an apparent conflict of interest.”

 

• Curriculum – 79; improved from 69 in 2011-2, 48 in 2010, 28 in 2009, and 12 in 2008.  To gain a perfect score, “Students are trained to understand institutional conflict-of-interest policies and recognize how industry promotion can influence clinical judgment.”

 

• Consulting (excluding scientific research and speaking) – 71, improved from 64 in 2011-2, 49 in 2010, 27 in 2009, and 12 in 2008.  To gain a perfect score, consulting relationships “must be subjected to institutional review or approval. Additionally, they must either be described in a formal contract, or payment for services must be commensurate to the task.” 

 

• Sales representatives – 4; improved from both 2 in 2011-2 and 2010, and both 1 in 2009 and 2008.  To gain a perfect score, “Pharmaceutical and device representatives are not allowed to meet with faculty regardless of location, or are not permitted to market their products anywhere inside the medical center and associated clinics and offices. (Exceptions may be made for non-marketing purposes, such as training on devices or equipment.)”

 

• Purchasing & Formularies – 83; improved from 70 in 2011-2, 66 in 2010, 47 in 2009, and 22 in 2008.  To gain a perfect score, “Formulary committees and committees overseeing purchases of medical devices should exclude those who have financial relationships with drug or device manufacturers.  Exclusion may be specific to participation in particular decisions for which the staff member has a conflict of interest.  This policy does not prevent expert clinicians from advising a committee, provided that potential conflicts are disclosed.  (Note: this standard is not intended to prohibit indirect financial interests, such as investments in mutual funds that may own pharmaceutical company shares).”  

 

• Samples – 42, improved from 31 in 2011-2, 26 in 2010, 20 in 2009, and 12 in 2008.  To gain a perfect score, “Industry samples are prohibited, except under certain narrow circumstances approved by the institution that protect the interests of patients and prevent the use of samples as a marketing tool (e.g., policies that allow samples under limited circumstances with the approval of the Pharmacy and Therapeutics (P&T) Committee or policies that incorporate samples into a larger program designed to ensure the availability of brand-name and generic medications to under-insured patients; if the circumstances of the specific program are not defined, the policy should define the approvals process). Where there is a specific program in place, the policy must prevent samples from being given directly to physicians by pharmaceutical sales representatives.”

 

• Industry-funded speaking – 44; improved from 31 in 2011-2, 19 in 2010, 10 in 2009, and 4 in 2008.  To gain a perfect score, “Speaking relationships are prevented from functioning as de facto gifts or marketing.  An effective policy must not implicitly permit (a) long-term speaking agreements or (b) industry to have a role in determining presentation content.  (Some effective policies may explicitly prohibit participation in a speakers bureau.  Other effective policies contain elements such as limits on compensation and reimbursement and a requirement to ensure the scientific integrity of information presented.)”

 

Similar to the results of the past, the areas that garnered the greatest number of perfect scores were those addressing industry support of scholarships, off-campus “CME,” faculty participation in industry-speaking relationships, purchasing and formulary committees, and gifts.  Industry support of scholarships experienced the largest net growth in achieving perfect scores in this domain (15 additional medical schools).  New areas being addressed by schools include samples as well as purchasing and formula committees.  AMSA says that “on-campus CME” remains a challenging area.

 

Regional Trends

Californian medical schools continued to excel with 7 of their 10 schools receiving an A grade.  This is in part due to the strong system-wide University of California (UC) COI policy, which when graded on its own receives an A grade.  However, some of the UC schools go even further by supplementing the system-wide policy with their own regulations.  Texan schools continue to show significant improvement.  All eight Texan medical schools score at least a B.  University of Texas Medical Branch at Galveston, however, remains the lone A in the Lone Star state.

 

Another major training ground, Massachusetts, continues to show case schools with model policies. This year, University of Massachusetts Medical School and Boston University both received a B grade while Harvard Medical School and Tufts University School of Medicine both received an A grade.

 

The nine Pennsylvania medical schools have strong policies and in Maryland, all three schools (Johns Hopkins University, University of Maryland, and Uniformed Services of the Health University) received a B grade or higher.  Finally, the state of Florida continues to perform well.

 

Methods

 

The PharmFree Scorecard methodology was developed jointly by AMSA and the Pew Prescription Project, an initiative of the Pew Health Group.  Assessed domains are broadly consistent with those identified in recent literature – primarily Brennan et al. Health Industry Practices that Create Conflicts of Interest:  A Policy Proposal for Academic Medical Centers.  JAMA 2006; 295(4): 429-433.

 

The Scorecard assesses policies related to: (1) acceptance of gifts and meals from industry; (2) consulting relationships; (3) speaking relationships; (4) disclosure of financial conflicts; (5) pharmaceutical samples; (6) individuals with financial conflicts participating in university purchasing decisions; (7) financial support for educational events (on- and off-campus); (8) industry support for scholarships and trainee funds; (9) access of industry sales personnel to medical school or hospital personnel; and (10) inclusion of education about conflict of interest within the academic curriculum. Additionally, the presence of oversight and sanctions is examined, but not included in grade calculation.

 

AMSA maintains that “Two blinded assessors independently score each set of policies in the eleven areas included in the scorecard.”  How can such assessors be blinded if they are working for AMSA/Pew, and are clearly anti-industry and biased towards any kind of industry interactions or collaboration?

 

Other AMSA Initiatives

 

Of particular interest is a new initiative known as the “2^nd Slide Campaign,” which is based off the standard practice in graduate and continuing medical education (CME) to disclose conflicts of interest on the 2^nd slide of one’s presentation.  “The premise of this campaign is simple: medical students should receive the same types of disclosures that educators provide in other types of medication.”  AMSA notes that “most medical schools lack clear guidelines to help faculty members disclose conflicts of interest to students.”

 

AMSA provides a sample disclosure slides and other information for medical students to bring about change in their medical schools. AMSA provides three scenarios for when a lecturer should disclose interests to students, and tailors their example disclosure slides to such scenarios:

 

-          Lecturer has conflicts of interest but they are not relevant

-          The lecturer has no conflicts of interest

-          The lecturer has relevant conflicts of interest to disclose to the students 

AMSA said that such disclosures matter because it is “vital” that medical students and “know where information comes from.”  AMSA calls for such disclosure because “research shows that financial conflicts of interest can impact (even subconsciously!)the presentation and interpretation of data.”  AMSA also has resourcs for a PharmFree Curriculum and “Best Practice Policies,” such as for gifts, meals, and samples.  

Given the already hurried schedules of physicians and medical students, will there really be enough time for medical professors to address and discuss potential conflicts with students?  Will such disclosures even matter to students?  It seems more appropriate that this subject be clearly addressed in a standard medical ethics course over the course of medical school, not during each lecture given, particularly in light of the Sunshine Act, which will allow medical students to do their own research on professors, if they desire.   

One interesting new program that AMSA appears to have started is the “National Opt Out Day.”  Specifically, AMSA “asked graduating fourth year members to tell the American Medical Association (AMA) that they are opting out of the AMA Physician Masterfile!”  “As physicians who strive to practice evidence-based medicine, we do not want our personal and prescribing information sold to the pharmaceutical and medical device industries.”  The AMA Physician Masterfile was established by the AMA in 1906 as a record keeping device supporting membership and mailing activities. The Physician Masterfile includes current and historical data for more than 1.4 million physicians, residents and medical students in the United States. 

AMSA also hosted a webinar with the University of Miami Miller School of Medicine to discuss how the school improved their conflict of interest policies as well as the barriers both current and past to implementing change.  Executive Dean of Education and Policy Dr. Laurence Gardner will be presenting. 

AMSA noted that in addition to Pew, it has joined forces with the National Physicians Alliance (NPA) and Community Catalyst to create both external and internal pressure for medical schools and academic medical centers to adopt strong COI policies, through a new initiative- the Partnership to Advance Conflict-Free Medical Education (PACME).  They noted how NPA’s Unbranded Doctor campaign provides resources for conflict-free medical practice including an archive of past events including bimonthly Conflict-Free Leadership Calls and National Grand Rounds. 

Community Catalyst is in the process of developing a series of toolkits to help institutions improve their policies with examples of language from other model institutions and provides technical assistance to schools via regional roundtable and individual consultation.

 

 

Medical Students Eating Lunches but Feeling Guilty

Eating lunches and feeling guilty is something we are supposed to do when we are older after we have gained some weight.   But now young medical students are having second thoughts on the meals they share with pharmaceutical reps. 

We have written extensively about the growing “conflict of interest mania” that has swept across our nation over the past few years.  One of the places this “mania” has touched the greatest is academic medical centers (AMCs) and/or medical schools.  In fact, each year, the American Medical Students Association (AMSA) publishes a yearly “PharmFree Scorecard” that evaluates the conflict of interest (COI) policies ant American medical schools.   

Of 152 US medical schools in 2012, 28 received “A”s (18%), 74 “B”s (49%), 15 “C”s (10%), and 13 “D”s (9%).  The areas that garnered the greatest number of perfect scores were those addressing industry support of scholarships, off-campus continuing medical education, purchasing, and gifts.  New areas of growth appear to be seen within the following three domains: curriculum, speaking, and consulting. Specifically, curriculum experienced the largest net growth in new schools with model policies (22 additional schools). Speakers relationships and consulting experienced an increase in an equal number of schools (16 schools) and the scholarships, gifts and off-campus education experienced large increases as well. 

Consequently, “researchers” recently surveyed 1,610 first- and third-year medical students and 739 residents regarding conflict of interest policies.  Among first-year students  

• 1/3 reported receiving gifts from pharmaceutical companies and
• 17% said they had talked with a pharmaceutical representative in the prior six months. 

Those percentages were significantly higher for third-year students.  

• Nearly four in five reported receiving gifts, which could include food, trinkets such as pens and paper, drug samples, or financial support.
• 44% said they had interacted with drug reps.
• The rates for residents were somewhat similar.  

The story, reported by the Boston Globe, quoted students at Brown University’s Alpert Medical School, who are prohibited from accepting gifts or meals from pharmaceutical companies and drug salespeople. Yet, when she was training in a primary care clinic, student Reshma Ramachandran said drug salespeople stopped by often -- sometimes four times each week -- bringing lunch for the staff.  The realities of practice clashed with her school’s policy.  

“The preceptor would encourage us -- and it was kind of a weird pressure -- to go and sit with the sales rep or to sit with them as they talked to the sales reps,” said Ramachandran, who is a fellow with AMSA, partly focused on conflict of interest polices at medical schools.  It is unclear why this would be “weird,” especially if her preceptor was just trying to show his/her students the realities of practice. 

The reality is, physicians—at all stages of their training—need to have interactions with industry.  Not only are such relationships beneficial for continuing medical progress and innovation, advancing medical care, and improving patient outcomes, but interactions also teach medical students and residents about the nature of the pharmaceutical and medical device industry.  More importantly, such interactions—particularly in the medical device world—are critical for teaching students and young physicians how to properly use a device or perform a procedure.  And such interactions and training are typically mandated by FDA in the devices’ clearance and mandatory medical device reporting requirements.

Thus, medical schools and AMCs should encourage and in fact require medical students and residents to interact with industry—not only to experience what such interactions have to offer, but also to better prepare them for their career.  Medical students need to realize that sales reps and medical affairs staff exist for a reason: because physicians don’t have enough time in a day to learn about all the new research, advances and updates in clinical care—including FDA REMS, safety updates, or black-box warnings. 

Moreover, as we wrote last year, physicians who restrict access to sales reps or who ignore sales rep are slower to respond or adjust their prescribing and treatment habits in response to negative news about the drug.  The authors of the study found that physicians with very low access to representatives had the lowest adoption of a new therapy and took 1.4 and 4.6 times longer to adopt than physicians in the low- and medium-access restriction categories, respectively.  In responding to the black box warning for rosiglitazone, the authors found that physicians with very low access were 4.0 times slower to reduce their use of this treatment than those with low access. 

Likewise, there was significantly less response in terms of changing prescribing to the negative news with the lipid therapy for physicians in more access-restricted offices. Overall, cardiologists were the most responsive to information changes relative to primary care physicians.  These findings emphasize that limiting access to pharmaceutical representatives can have the unintended effect of reducing appropriate responses to negative information about drugs just as much as responses to positive information about innovative drugs. 

Nevertheless, despite the growth in COI policies, even at institutions with the strictest rules, the new study claims that “many doctors-to-be are exposed to pharmaceutical marketing throughout their training, according to study published this week by the Journal of General Internal Medicine and led by researchers at Harvard Medical School.” 

Those students who attend schools with more comprehensive policies, measured on the medical student association’s scorecard, were no less likely to have those contacts with salespeople, the study found. 

“Having the policy on the books is one thing,” said senior author Dr. Aaron Kesselheim, a Brigham and Women’s physician and assistant professor of medicine at Harvard Medical School. “Making sure that it’s implemented and isn’t being skirted around with off-campus interactions and interactions at hospitals which the medical students might then go to is also important.”  

Blaming her school’s policy, Ramachandran would politely decline the chats with drug salespeople.  But, she said, it was difficult for some classmates to reject invitations, sometimes to fancy pharma-sponsored dinners, from supervisors who were responsible for grading their performance.  

One-third of first-year and most third-year students reported observing physicians or residents interact with a sales representative.  Kirsten Austad, a fourth-year medial student at Harvard and lead author on the paper said medical school is “a process of socialization,” and doctors learn what is ethical and appropriate not just from what they are taught but in how they see physicians behave. 

Marcia Boumil, assistant dean for conflict of interest administration at Tufts University School of Medicine, said though many physicians believe they are beyond being influenced by free lunches and samples, drug companies spend money on such efforts because they do affect prescribing practices.  

Tufts professors start talking about the effects of marketing to first-year students and repeat the message often throughout their training, Boumil said.  Students are prohibited from meeting with drug salespeople or accepting meals from them, on or off campus, but “whether or not we can monitor and enforce it is another story,” she said. 

Boumil said young doctors are changing the ethical standards in medicine as more who are trained in conflicts of interest begin their practice.  “A generation from now, I hope that the discussion will have changed, but just think about how much its changed in the past 10 to 20 years,” she said. “It’s gone from routine drug lunches every day, without question, to a lot of schools and hospitals having policies and talking about it and teaching about it and devoting class time to it.”  

Notable AMSA Trends 

One area deserving of particular attention is the growth of restrictions on speaking arrangements.  Seventeen of the thirty-two schools with restrictions on speaking arrangements took the lead by explicitly banning participation by their faculty on speaker’s bureaus.  The following is a list of domains and the number of perfect scores: 

• Scholarships – 108; from 94 in 2010, 66 in 2009 and 29 in 2008
• Off-campus continuing medical education – 88; from 75 in 2010, 49 in 2009 and 23 in 2008
• Gifts & Meals– 81; from 66 in 2010, 44 in 2009 and 19 in 2008
• Purchasing – 70;  from 65 in 2010, 47 in 2009 and 22 in 2008
• Curriculum – 69;  from 47 in 2010, 28 in 2009 and 12 in 2008
• Consulting – 64;  from 48 in 2010, 27 in 2009 and 12 in 2008
• Speaking – 32;  from 18 in 2010, 10 in 2009 and 4 in 2008
• Samples – 31;  from 26 in 2010, 20 in 2009 and 12 in 2008
• Disclosure – 29;  from 20 in 2010, 5 in 2009 and 1 in 2008
• On-campus continuing medical education – 20;  from 15 in 2010, 3 in 2009 and 5 in 2008
• Sales representatives – 2; unchanged from 2 in 2010, and both 1 in 2009 and 2008

2012 AAMC/SACME Harrison Survey of Academic Medical Centers Links CME to Quality Improvement

Since 1981, the Society for Academic CME (SACME) Research Committee has surveyed continuing medical education (CME) units at medical schools in the U.S. and Canada.  Beginning in 2008, the Association of American Medical Colleges (AAMC) partnered with SACME to prepare this report.  The Biennial Survey of Society members includes questions about the organization of the CME unit, its relationship to the larger organization in which it resides, the ‘product’ of the CME unit (courses and other activities and interventions), its funding base, research and innovation, and other items related to the operation of the CME unit. 

The survey is electronically distributed to all U.S. and Canadian medical schools, teaching hospitals in the U.S., and clinical academic societies who are members of the AAMC’s Council of Academic Societies (CAS).  We covered the survey in 2010 and 2009.  Consequently, SACME recently released its 2012 data. 

The fifth iteration of the annual AAMC/SACME Harrison Survey documents a highly  viable and robust academic enterprise increasingly integrated into the functions and  mission of the academic medical centers (AMCs) and medical schools of the U.S. and

Canada.  While there are several limitations to interpretation of this survey, the survey generates broad but important findings for discussion and analysis, namely: 

• An increasing linkage of the academic continuing medical education (CME) unit to  the quality and performance improvement programs and initiatives of the hospital  and health system. In particular, extensive interaction among these areas has grown from below 10 percent to more than 15 percent since 2008, and the relationship has  become increasingly important over a five-year period.
• Continued well-developed relationships with programs for other health  professions, graduate medical education (GME), and faculty development; however,  missed opportunities for the academic CME unit and the AMC in building  collaborations with faculty practice plans, undergraduate medical education,  hospital accreditation, and other functions.
• A clear trend to assess outcomes beyond the scope of the traditional post-course  ‘happiness index’ using a variety of methods to assess competence, performance,  and patient outcomes to evaluate their impact on the health system.
• Growing institutional support, demonstrated by comparing median institutional  support to full-budget figures, representing commitment on the part of most, if not  all, institutions in support of academic CME.
• A widespread commitment to regional community-based hospitals, health  systems, and health professionals, reflected in a growing array of educational  methods, including academic detailing. This regional alignment is important to  considerations of ’accountable care’ structures.
• Increasing use of evidence-based educational methods that have been shown to  more frequently change clinical performance over a five-year period.
• A reasonably steady, if still relatively small, cohort of CME units committed to  scholarship that contribute to the research enterprise in health professional learning  and change, the product of collaboration both within and across AMCs, derived  from funding sources internal and external to the institution. 

“Thus, academic CME demonstrates, despite external financial and regulatory pressures  (and perhaps because of them), several major changes over a five-year period,” the report maintained.  “There is  evidence of an increasing integration into the functions of the AMC; an uptake in the  use of effective educational methods; a wide variety of outreach activities geared to the  needs of the communities served by AMCs; and an impressive, if not yet widespread,  record in scholarly activities and best practices.” 

Methods 

In June and July of 2012, an Internet search identified a total of 465 academic CME  units that comprised 315 U.S. teaching hospitals, 17 Canadian medical schools, and  133 U.S. medical schools for whom a defined CME office and/or institutional contact  information could be identified, and/or in which a central national or regional CME  office did not accredit the activities (e.g., VA hospitals).  

Regarding medical schools, only 45 academic CME units represented U.S. medical schools, while all 17 Canadian medical schools were represented by  CME units.  An additional 88 CME units in the U.S. indicated that they provided CME services to both their medical school and one or more teaching hospitals or health care systems, for a total of 150 such institutions. 

In all, this generated a total of 239 academic CME units—17 Canadian medical schools, 133 U.S. medical schools, and 89 teaching hospitals/health care systems, with cross-representation as indicated above.  The 2012 Harrison Survey report describes: 

• response rate and characteristics of the respondents
• mission and scope of activities of academic CME units
• organization of AMCs in relationship to their CME units
• use of effective CME methods
• funding issues in academic CME
• research, development, and best practices 

Of the 239 eligible CME units in U.S. teaching hospitals and in U.S. and Canadian  medical schools, 184 (77%) responded to the survey.  Of these, roughly 94% were U.S.- based and 6% Canadian-based.  One hundred twenty-seven (79% of all respondents)  reported national accreditation in the U.S. by the ACCME and 22 (14%) by state  accrediting agencies.  All 12 reporting Canadian schools (6% of the total) indicated accreditation by the Committee on Accreditation of Canadian Medical Schools  (CACMS).  

• Roughly three-quarters (76%) of these sites provided quality and  performance improvement activities, or planning and continuing education for  an inter-professional audience.  
• Similar percentages provided clinical professional development for faculty and staff and faculty development to improve teaching skills.  
• Of interest, 35% provided at least a small number of noncertified educational services, and
• 15% provided patient or public education programming.  

In addition to reporting staff with responsibilities in educational development, event planning, and support roles, CME units also reported staff expertise in: 

• Research and grant writing
• Accreditation and compliance
• Business analysis and operations
• Marketing and Communications
• Academic detailing
• Strategic affairs and planning 

Developing activities to achieve the missions of the academic medical center (AMC) requires an understanding of the organizational and reporting structures of CME units in modern health care settings. 

Internal Relationships 

The relationships developed within the AMC foster the achievement of goals of the entire center and those of the academic CME unit.  Respondents were provided a list of programs, departments, or units internal to the AMC, which may exist in their respective settings.  These included faculty development programs, library services, conflict of interest committees, medical student or resident educational programs, compliance education, physician performance or quality improvement units, faculty practice plans, continuing education for other health professions, health services research, public health, employee or staff professional development, and public education. 

Further, respondents were asked to describe the relationship between the CME office and each of those programs on a scale ranging from no or minimal interaction to

extensive interaction. In this case, minimal interaction was described as “irregular or occasional activity linked to the program or unit,” while extensive interaction was characterized as “ongoing planning or developmental activity, conjoint programming, shared goals and strategic directions, or shared resources.”  Of the 91 U.S. medical school-based units shown in 

• 74% indicated a combined moderate/extensive interaction with continuing education programs for other health professions,
• 62% described similar interactions with physician or hospital quality improvement programs, and
• 61% expressed a combined moderate/extensive interaction  with faculty development programs. 

One area represents an important change in the degree of interaction over a five-year period.  Previous Harrison Survey reports described relationships with QI/PI functions as fifth in frequency in 2008, with combined moderate to extensive interaction at roughly 58%.  In the 2012 survey, relationships with QI/PI now place second among relationships.  Further, the percentage of those selecting extensive interaction has also grown, accounting for virtually the entire growth in this area.  From 2008 to 2012, the total of combined moderate/extensive interaction improved from 58% to 63%, the product of growth in the ‘extensive interaction’ category. 

Also reported at levels of greater than 50% in this year’s survey was involvement at moderate or extensive levels with conflict of interest committees, with graduate or residency medical education, and with the allied health professions. Several interactions were much less frequently reported, providing examples of opportunities for academic CME, and the AMC itself.  

The 2012 Harrison Survey focuses on four aspects of programming that reflect a growing awareness of the literature driving changes in the delivery of continuing education and professional development activities, making them more effective in the process, namely: 

• use of evidence-based methods in regular course planning, implementation, and  follow-up
• use of assessment methods to determine the effect of these activities
• growing use of alternative methods and strategies to reach a diverse audience  external to the AMC
• role of faculty development 

Rigorous research evidence, including systematic reviews, demonstrates the positive effect on health professional performance when research-based educational methods are employed.  In particular, this research encourages CME providers to: 

• Use objective data and understand barriers to change as they plan activities (e.g.,  employing quality data in planning and development).
• Increase the use of interaction in planned educational sessions (e.g., by using case  discussion methods or simulations, or by providing in-program practice aids such  as flow charts).
• Employ sequential learning so that practice and education are mutually reinforced. 

Since the first AAMC/SACME Harrison Survey in 2008, respondents have been asked about the use of these methods, along with other activities in pre-activity planning, course development, and post-course evaluation.  

Pre-activity Methods 

Reported here are several pre-activity planning methods.  Among them, planning based on quality metrics to augment subjective needs assessments appears to be an important, evidence-based step.  Of the 145 reporting CME units, 

• 80% indicated regular use and 19% reported occasional use of these methods.  
• 47% percent occasionally and 35% regularly have developed meaningful interprofessional planning methods,
• 37% occasionally and 41% regularly consider barriers to changing professional performance.
• Only 40% of units occasionally or regularly undertake presenter training  of professional development in order to train these presenters in more effective  methodologies. 

Academic CME providers report using evidence-based educational methods—objective needs assessments, teaching methods such  as interactivity and simulations,  and post-activity follow-up—to a  significantly greater extent over a  five-year period. 

Several evidence-based educational methods in courses and conferences themselves are also reported as occasionally or regularly used by academic CME providers.  Chief among these was the use of ‘interactivity,’ defined as devoting more than a quarter of educational time to case discussion, audience interaction and participation, and/or question/answer sessions.  The majority of CME units reported employing such methods to a significant extent (>25% of programming time), with 60% reporting interactive techniques and methods regularly.  Other effective methods used regularly or occasionally included: 

• practice facilitators or enablers such as flow charts for use in the practice setting (81%),
• evidence-based tools and resources (69%),
• simulations (69%), and
• team-based learning (64%).
• Only 45% used methods described as  sequential i.e., learning sessions separated by practice periods, in which new knowledge  or skills can be acquired and then built upon in further educational sessions. 

Post-program Methods 

Respondents were asked about the use of quality metrics to assess the impact of their programs: 75% did so either regularly or occasionally.  In addition, adopting the research evidence that reinforcing strategies enabled the uptake of knowledge and practice change, respondents were asked if they followed up with their program participants post-course—emailing new information, reinforcing commitments to change, asking further questions—and 70 % reported doing so, more than half regularly.

Comparison with the first (2008) AAMC/SACME Harrison Survey report provides an instructive means to judge progress in academic CME.  Several items have been tracked annually or semi-annually since the publication of that report; the 2012 Harrison Survey report demonstrates a progressive change towards the current picture.  2008 data, in particular demonstrating: 

• the use of quality or performance improvement as needs assessment occasionally or  regularly (85%)
• in-program practice enablers (61%)
• simulations (56%)
• post-performance quality measures to track the outcomes of educational activities (54%)
• follow-up methods to reinforce participant learning (64%) 

Beyond the post course ‘happiness index’, many academic CME providers use measures of competence, self-reported or actual performance data, and (a smaller number) patient and population health data.  New to the 2012 survey, respondents were asked to indicate what percentage of activities used the outcomes measured. 

• 63% percent of respondents’ activities involved measures of competence (e.g., post-course multiple choice examinations),
• 40% employed general, self-reported performance measures,
• 16% used objective data such as quality measures to track outcomes,
• while smaller percentages (13% and 9% respectively) measured  actual patient or population health outcomes.  

When asked the question, “Does your CME unit participate in faculty development activities,” 119 units, or 84%, indicated ‘yes’.  The majority of these activities involved educational or accreditation aspects of faculty development that touched upon the teaching methods in UME, GME, and CME.   

• 91%had responsibilities of some type for CME teaching,
• 61% for GME (or in Canada PGME) teaching, and
• 52% for UME teaching improvements.  

This percentage of activity has remained relatively stable over several years.  One hundred and four CME units also reported some responsibility for faculty development activities involving basic research, regulatory matters, or clinical issues.  Ninety-six units (92%) developed faculty-focused activities in clinical issues such as team training or quality improvement, and 60 units (58%) in the area of basic research (e.g., regulatory, conflict of interest, or ethical issues). 

Reaching Out: Serving the Regional Community 

In addition to providing traditional courses and conferences, academic CME providers also reach out to regional community-based practitioners.  Respondents reported using live teleconferencing (audio or video) methods, visiting speakers’ programs, opinion leader, and train-the-trainer activities, academic detailing, social networking, and other means.  

Regional health professionals and systems are also served by academic CME providers, using teleconferencing, opinion leader and train-the-trainer programs, and (to a lesser but growing extent) social networking methods. Academic detailing—outreach visits by trained health professional—appears to have undergone substantial growth over a five year period.  Out of 140 respondents, CME providers said they engaged inthe following types of activities: 

• over 80% live teleconferences (video, audio, webcasts)
• over 70% visiting speakers at medical society or community hospital meetings series
• over 60% opinion leader/Train-the-Trainer programs
• almost 50% academic detailing
• over 40% individual traineeships or tutorials
• over 35% communities of practice
• ~35% learning/individuals coaching programs
• ~35% social networking 

Academic Detailing 

50% of CME units reported the use of academic detailing—educational visits by trained health professionals to individual or team-based physicians.  This method has been demonstrated to improve prescribing and health promotion/screening performance to at least a moderate extent.  Academic CME units have reported a steady rise in the numbers of such programs, from under 10 in 2008 to almost 70 in 2012 (an increase from ~45 in 2011). 

Academic CME Budgets 

For calendar year 2011, CME units were asked about the size of their total fixed  operating budgets, reflecting a wide spread of means, medians, and budget ranges by  institution type.  Less variability was noted among the eight reporting Canadian medical schools, which indicated budgets with the following characteristics: a median of $1.3 million, a maximum of $4.5 million, and a minimum of $364,000. 

In contrast, the 90 U.S. medical schools reported lower median budget figures (by roughly $500,000), but greater variability ($11.8 million in maximum, $25,000 in minimum).  CME Fixed Operating Budget (127 respondents) 

• Mean budget for U.S. Medical School $797,097
• Median budget U.S. Medical School $497,506

Even more variability was noted among U.S. teaching hospitals.  Twenty such units reported median figures of $275,000, indicating a maximum of $30 million and a minimum of $5,000. 

• Mean budget for Teaching Hospital $2,126,509
• Median budget for Teaching Hospital $275,000 of which $200,000 was derived from institutional (hospital and health system) sources—roughly 80%. 

The total revenue from institution to CME Unit (128 respondents) 

• Mean U.S. Medical School $235,536
• Median U.S. Medical School $141,461
• Mean Teaching Hospital $1,307,074
• Median Teaching Hospital $200,000 

Among Canadian medical schools with median budgets averaging $1.3 million, just under $400,000 (roughly one-third) come from institutional sources.  U.S. medical schools reported slightly less than $500,000 in median total revenues (though a wide range) and $141,000 in median institutional support (slightly under one-third).  

The 2012  survey asked the question, “As a percentage of the fixed CME budget, has institutional  support increased, decreased, or stayed the same in the last year?”   

• 54% of respondents indicated similar year-to-year support,
• 16% indicated an increase in support, and
• 30% a decrease. 

Research Activity 

Research activity is reported by a sizable minority of academic units, primarily in medical schools—totaling millions of dollars and over two hundred studies.  Research includes formal evaluation processes related to physician or health professional learning, the effect of CME, the outcomes derived from educational activities, and related matters.  Some research was externally funded by peer review or commercial sources, and some internally funded.  In the U.S. and Canada, 43 units reported research activity.  These units undertook:  

• a median of two research studies.
• 22 respondents indicated receiving grant support for CME-related research studies greater than $0. 
• The maximum reported grant for those with support was almost $10 million. 
• The minimum was $20,000, with the mean $924,337 and the median $70,000. 

Collaboration Within and Across CME Units 

Those units reporting research activity were then asked to what extent these studies were either cross-institutional or collaborative within the institution and/or multi-institutional.  The majority of respondents reported undertaking both cross- and multi-institutional studies.  86.4% said they engage in cross-institutional or collaborative research within their own institution (51 respondents), while 57.9% said they had multi-institutional or collaborative research with other medical institutions (33 respondents).  

Examples of research include: outreach activities, PI-CME or quality improvement strategies, personal learning programs, faculty development, and others; knowledge translation or implementation science; new technologies such as those in social networking or blended learning; new audiences including allied health professionals, patients, and public members; planning and assessment strategies; and outcomes assessment methods.  A host of administrative, financial, organizational, and collaborative activities were also described. 

Limitations of Survey 

There are several limitations to the interpretation of this survey.  First, the survey is based on a self-reported questionnaire to which 77% of academic CME units responded.  Thus, responses are absent from one-quarter to one-third of academic CME units.  Notably, traditionally defined teaching hospitals in the U.S. have not generally been the target of these surveys and are not, as a rule, members of the major co-sponsor of this survey—the Society for Academic Continuing Medical Education.  

Further, between-year comparisons may be marred by a sampling of non-identical CME units and by questions which have been worded slightly differently, the result of an ongoing process to improve the clarity of the questions asked.  Finally, the wide variation in reporting of some figures (e.g., those related to the budget) makes judgment difficult and casts some doubt on respondents’ understanding of specific questions; median figures were used in this regard.  

Academic CME: Internal Alignment and Value  

The first notable feature of this year’s report, when compared to similar surveys over a five-year period, is the increasing linkage of the academic CME unit to the quality and performance improvement programs and initiatives of the hospital and health system. In particular, extensive interaction has grown from below 10% to more than 15% since 2008, and the relationship moved from fifth to second place during this time.  Also apparent is a well-developed relationship internally with CE programs for other health professions, with GME, and, notably, with faculty development.  These linkages across the medical school, teaching hospital, and clinical settings appear to make the traditional teaching hospital and medical school structures arbitrary at best, leaving the clear conclusion that there exists an entity—academic CME—with significant roles and demonstrated impact within the AMC.  

The process of alignment, however, is not universal across sites and systems and appears to neglect areas of possible interest to continuing education providers and the AMC— namely building relationships with faculty practice plans, undergraduate medical education, hospital accreditation, and other functions.  Further, staffing of academic CME units rarely includes individuals skilled in such areas as quality measurement or performance improvement.  At a minimum, these observations identify missed opportunities.  

Academic CME providers appear to use a variety of methods to assess competence, performance, and even patient outcomes to evaluate their impact on the health system. A further, if arguable, means of assessing the degree of integration of academic CME into the mission of the AMC, is to judge the extent of funding support from institutional sources.  This, at least by comparing median institutional support to full-budget figures, notes a sizable commitment on the part of most, if not all, institutions that support academic CME. 

Research, Scholarship, and Evidence-based Education: How Academic is ‘Academic’ CME?  

First, and most notably, academic CME programmatic commitment appears to be more evidence-based over a five-year period, i.e., employing educational methods that have been demonstrated to more frequently change clinical performance.  These methods include pre-activity planning (e.g., using quality metrics as an objective means to determine performance), intraprogram activities (sequencing of learning activities, creating interactivity, and using enabling materials such as flow sheets and patient educational materials to support change in the clinical setting), and post-course methods to reinforce learning.  The growth in use of these methods over a five-year period is notable.  

This shift from traditional, didactic, and, thus, marginally effective CME, reflects more than just a contemporary trend. Instead, it demonstrates—much as the practices of academic physicians do—the uptake of best evidence with regards to practice.  In this case, the practice is educational and reflects the undertaking of scholarship, research, and study, to analyze the effect of educational interventions, to test new ones, and to study their outcomes.  

Second, it appears that there is a reasonably steady, if still relatively small, cohort of CME units which are committed to scholarship and which contribute to the research enterprise in health professional learning and change. This commitment is the product of collaboration both within and across AMCs, and is derived from funding sources internal and external to the institution.  

The 2012 Harrison Survey also makes apparent a strong commitment, equal to its internal integration, to regional community-based hospitals, health systems, and health professionals.  This is reflected in a growing array of educational methods such as teleconferencing, online learning activities, opinion leader and train-the-trainer programs, and the growing use of social networking to link to community-based health professionals. In addition, the growth of academic detailing during this time further shows CME providers’ innovation and attention to effective educational engagement and an awareness of external funding opportunities in this area.  Finally, this regional alignment is important to considerations of accountable-care structures in which community-based health professionals—and the linkage that academic CME represents to them—play a large and important role. 

Conclusion 

Academic CME demonstrates, despite external financial and regulatory pressures (and perhaps because of them), several major features: evidence of an increasing integration into the functions of the AMC; an uptake in the use of effective educational methods; a wide variety of outreach activities geared to the needs of the communities served by AMCs; and an impressive, if not yet widespread record in scholarly activities and best practices.  

Challenges are also presented in this report.  Academic CME providers, AMC leadership and faculty need to create significant, functional alignments among CME and other relevant internal units, and enhance community engagement strategies and methods. Support for and an understanding of the potential role of academic CME units in scholarship in improving patient care and in achieving other missions of the AMC remain incomplete and patchy.

Strict Conflict of interest Policies at Academic Medical Centers Lead to Prescribing Older Generic Drugs

We have dedicated a large portion of this blog to covering “conflicts of interest” or COIs, and the various claims being made about the potential influence COIs may have on physicians, researchers, and CME providers.  COIs raise concerns because often, the latter group of individuals have relationships with industry—whether consulting, research, advisory, or other—that cause some to believe that those same individuals cannot remain impartial when writing prescriptions or teaching colleagues or even students. 

Consequently, a recent study, published in the British Medical Journal (BMJ) found that doctors who attended medical schools that limited gifts to students from pharmaceutical companies -- sponsored lunches, for example -- may be less open to drug marketing.   

The objective of the study was to “examine the effect of attending a medical school with an active policy on restricting gifts from representatives of pharmaceutical and device industries on subsequent prescribing behavior.” 

Interestingly, the study was funded by the National Institute of Mental Health (NIMH), the National Institute on Aging, the American Federation on Aging, and NIH.   Which we all know means the study is completely unbiased. 

Specifically, the authors looked at the probability that a physician would prescribe a newly marketed medication over existing alternatives of three psychotropic classes: lisdexamfetamine among stimulants, paliperidone among antipsychotics, and desvenlafaxine among antidepressants.  “None of these medications represented radical breakthroughs in their respective classes,” according to the authors. 

For two of the three medications examined, attending a medical school with an active gift restriction policy was associated with reduced prescribing of the newly marketed drug.  Physicians who attended a medical school with an active conflict of interest policy were less likely to prescribe lisdexamfetamine over older stimulants and paliperidone over older antipsychotics.  A significant effect was not observed for desvenlafaxine (1.54, 0.79 to 3.03; P=0.20).  Among cohorts of students who had a longer exposure to the policy or were exposed to more stringent policies, prescribing rates were further reduced. 

Thus, the authors concluded that “Exposure to a gift restriction policy during medical school was associated with reduced prescribing of two out of three newly introduced psychotropic medications.”   

One of the major weaknesses of this study is that the authors used students who have recently graduated from medical school within the last five years.  Thus, their prescribing habits are likely to change significantly over time as they gain more experience, training and knowledge about the diseases they treat and drugs they use.  It may seem obvious that these individuals are hesitant to prescribe these drugs because they have been brainwashed during medical school to think any brand-name medication is evil and if there is marketing on such drug to outright ignore that information—despite the harm this may have to patients about important safety updates. 

In fact, the authors acknowledged that “In instances where the newly introduced medication is a noticeable improvement over alternatives,” such an effect (e.g., not prescribing it) “could slow the diffusion of medical advances.”  However, in instances instances “where the newly introduced medication offers no additional benefit to patients, such an effect may limit the unnecessary use of newer, more expensive brand name medications, potentially slowing the escalation of healthcare costs.” 

Moreover, what is also problematic about this study is that it does not attempt to reconcile patient outcomes with these prescribing patterns.  In other words, we don’t know whether the patients not receiving these prescriptions are doing better, worse or the same.  For all we know, these recent graduates are prescribing drugs that might be harming patients or causing poorer outcomes, leading to higher costs in the future and lower quality of life. 

Additionally, another major weakness of this study--as was pointed out to us by our colleagues--is that the authors attempt to group pharmacetuical and medical device manufacturers and their relationships with AMCs and physicians into the same category.  While AMC policies may lump together pharma and device interactions, that does not mean they are equivalent to one another, something the authors failed to analyze or assess.  Nothing in the article justifies even the slightest mention of the medical device industry and the device industry is vastly different from pharma. 

Often, interactions with medical device manufacturers are required, and indeed necessary in some cases to achieve the proper standard of care to perform a procedure.  Moreover, and most often, the inventor of a particular device or technique must give hands-on training to physicians--either at the manufacturer's office or on-site, to ensure that physicians can implant or use the device in compliance with its FDA clearance.  In fact, many FDA clearance letters for medical devices--particularly for high-risk, Class III devices--mandate that the manufacturer provide specific training and show proof of such training through annual medical device reporting.  The study's failure to acknowledge this is problematic and shows their misunderstanding of the device industry and the importance of their interactions, training and education with physicians.

Another similar study, published in the February Issue of Medical Care, found that “Psychiatrists exposed to conflict-of-interest (COI) policies while completing their residency program are less likely to prescribe brand-name antidepressants after completion of their residency. 

Andrew J. Epstein, Ph.D., of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues used 2009 prescribing data from IMS Health to compare the prescribing behavior of 1,652 psychiatrists from 162 residency programs. The authors sought to determine whether exposure to COI policies during residency affected antidepressant prescribing behavior after training completion. 

About half of the residents graduated in 2001, before COI training guidelines were implemented, and the remaining half graduated in 2008, after COI adoption.  The researchers found that prescription rates for heavily promoted, brand-name, or reformulated antidepressant medications were lower for those graduating in 2008, after COI adoption, but were lowest for those programs with the most restrictive COI policies. 

“In psychiatry, we found that physicians who were exposed to maximally restrictive COI policies during residency training had lower rates of prescribing heavily marketed antidepressants,” the authors write.  “Although physician-industry interactions may serve an important informational function, our results offer one piece of evidence that these COI policies have helped inoculate physicians against the persuasive aspects of pharmaceutical promotion.” 

BMJ Study  

As background for their study, the authors noted that the American Medical Student Association (AMSA) established a PharmFree Campaign to advocate for evidence based, rather than marketing based, prescribing in 2002.  In 2007, AMSA released the first “PharmFree scorecard”, which graded US medical schools on the presence or absence of a policy regulating interactions between students and faculty and representatives of the pharmaceutical and medical device industries.  Since the first PharmFree scorecard was adopted, the number of US medical schools with conflict of interest policies has grown exponentially and most now have policies restricting gifts. 

Studies conducted before the PharmaFree Campaign found that most medical students were exposed to marketing efforts during their medical education.  On average, students either received a gift or attended an industry sponsored event weekly.  “Exposure to marketing efforts by the pharmaceutical industry during medical school has been associated with favorable attitudes towards the pharmaceutical industry.”  

Furthermore, marketing efforts have been shown to reduce the time to new drug adoption and increase the probability that a physician will adopt a new drug.   

Research has found that educational interventions strongly influence students’ attitudes toward pharmaceutical marketing and are associated with increased support for policies banning interactions between representatives of pharmaceutical companies and students.  Similarly, students attending a medical school with restrictive marketing policies tend to have less favorable attitudes about promotional items than their peers who were not exposed to a conflict of interest policy and are less likely to trust the advice they receive from representatives of pharmaceutical companies.  

Although research has found that educational interventions and conflict of interest policies are associated with increased skepticism about pharmaceutical marketing, the effect of medical school gift restriction polices on subsequent prescribing remains unknown.  Accordingly, the authors studied the impact of attending a medical school with a gift restriction policy on the adoption of new drugs.   

Overview and Methodology  

To see whether attending a medical school with a gift restriction policy affected prescribing of new drugs, they used a difference-in-differences design to compare prescribing patterns of physicians who attended a school with a gift restriction policy when the policy was in place with those of physicians who attended the same school before the policy was in place, as well as with the prescriptions written by two matched control groups. 

The authors used prescribing data from IMS health on the three drug classes July 2008 and March 2009.  Using internet searches, as well as information contained in the Institute of Medicine (IOM) as a profession’s conflict of interest database and AMSA’s PharmFree scorecard, one investigator either determined the initial implementation date of the gift restriction policy for medical schools that had a policy or verified that the school did not have a policy in place by the end of the study period.  They also looked for revision dates if policies were changed or updated and verified these as well. 

The authors identified 14 medical schools with a policy that explicitly prohibited or restricted gifts as of 2004.  A restrictive cut-off date of policy implementation by 2004 was necessary to allow for the average time required to complete postgraduate residency training after graduation from medical school for physicians to be eligible to independently prescribe medications by July 2008, the beginning of our prescribing observation period.  Many of the schools that had a policy in place by 2004 had adopted policies as a result of state laws or military restrictions governing gifts.  The policies varied in strength from almost complete bans on gifts to much weaker and ambiguous restrictions.   

Next the authors identified two cohorts of physicians to permit comparisons among those who attended the same medical school before and after implementation of a gift policy.  The first cohort included physicians that graduated two years before the policy was implemented and therefore were not exposed or affected since the policy was enacted after they had graduated.  The second cohort graduated in 2003 or 2004, after implementation of the policy.   

To account for changes in prescribing over time, the authors created a matched control sample composed of physicians who graduated from 20 different medical schools that adopted a policy restricting gifts in 2008.  These physicians were never exposed to the policy since they graduated before implementation.  

To determine the effect of gift restriction policies during medical training on prescribing as physicians, the author examined physicians’ propensity to prescribe newly introduced and marketed psychotropic medications over older medications in the same class.  During the study period, antipsychotics, antidepressants, and stimulants were among the top selling classes of medications, with US sales ranks of 1, 5, and 15, respectively.  Stimulants, antidepressants, and antipsychotics were also among the most promoted classes of medications.  

Given the importance of these three classes of medications to the pharmaceutical industry, the authors identified a newly marketed medication in each class for our study: lisdexamfetamine (Vyvanse; Shire, Wayne, PA) among stimulants, paliperidone (Invega; Janssen Pharmaceuticals, Titusville, NJ) among antipsychotics, and desvenlafaxine (Pristiq; Pfizer, New York, NY) among antidepressants. Lisdexamfetamine was introduced in March of 2007, paliperidone in December of 2006, and desvenlafaxine in February of 2008.  

Although the drugs examined in the study vary in their level of innovation, none represented radical breakthroughs in their class and all relied on mechanisms of action already available on the market.  These medications were the only oral medications within the three classes of data that we had access to that were approved within our study period. 

Results 

In total, 27.8% of prescribers wrote at least one prescription for lisdexamfetamine, 8.7% at least one prescription for paliperidone, and 6.9% at least one prescription for desvenlafaxine.  There were compositional differences between schools that adopted gift restriction policies before 2004 and later adopters, as well as between cohorts, in specialty composition and methods of payment. 

Stimulant Prescribing:  Physicians who were exposed to a gift restriction policy during medical school were significantly less likely than non-exposed physicians to prescribe lisdexamfetamine over older stimulants.  Of prescriptions written by physicians who attended a medical school with an active gift restriction policy, 5.9% were for lisdexamfetamine, in contrast with 7.4% among physicians not exposed to a policy who graduated from the same school before the policy was implemented.   

Among matched controls attending a school that implemented a policy in 2008, 8.3% and 9.1% of prescriptions were for lisdexamfetamine among earlier and later graduates, respectively.  Using a difference-in-differences approach showed that attending a medical school with an active conflict of interest policy significantly reduced the odds that a physician would prescribe lisdexamfetamine, the newly introduced stimulant, over older stimulants.   

In addition, for physicians who attended a medical school in which they would have been exposed to a policy for longer than the group exposed to the policy, the odds of prescribing lisdexamfetamine was further reduced.  Attending a school with a strong active policy also reduced the odds of prescribing lisdexamfetamine. 

Antipsychotic prescribing—paliperidone:  Physicians who were exposed to a gift restriction policy during medical school were significantly less likely than non-exposed physicians to prescribe paliperidone over older antipsychotics.  Of prescriptions written by physicians who attended a medical school with an active gift restriction policy, 0.5% were for paliperidone, in contrast with 1.7% among physicians who were not exposed to the policy and graduated from the same school. 

Among matched controls attending a school that implemented a policy in 2008, 1.2% and 1.4% of prescriptions were for paliperidone among the earlier and later cohorts, respectively.  Using a difference-in-differences approach, attending a medical school with an active conflict of interest policy was associated with a significantly decreased odds of prescribing paliperidone, the newly introduced antipsychotic.   

Antidepressant prescribing—desvenlafaxine:  Exposure to a gift restriction policy during medical school was not associated with differential prescribing of desvenlafaxine.  In all three models using a difference-in-differences approach, attending a medical school with an active gift restriction policy was not associated with significantly decreased odds of prescribing desvenlafaxine, the newly introduced antidepressant.   

In the main model, the odds ratio for students exposed to an active conflict of interest policy was 1.54.  Results were also insignificant in models examining students who were exposed to the policy for a longer duration or were exposed to a stricter policy.  

Discussion 

Implementation of a policy to restrict the receipt of gifts from the pharmaceutical industry at US medical schools was associated with significantly reduced prescribing of two out of three newly marketed psychotropic medications among students once they reached clinical practice. The odds of prescribing a newly marketed stimulant and a newly introduced antipsychotic medication were reduced among physicians who graduated from a medical school that had an active gift restriction policy.  The propensity to prescribe these two newly introduced medications was further reduced if the students were exposed to the policy for a longer duration or if the policy was relatively stringent.  

While these findings may suggest the ability to reduce prescribing of newly marketed pharmaceuticals, it remains yet to be seen whether such findings will result in only lower costs, or also better patient outcomes.  There is a significant chance, particularly given the complex nature of many of these drugs and the diseases they treat, that failing to prescribe new drugs may only further harm patients. 

Industry, Academic, Foundation and Government Alliances Continue in Early 2013

As promised, we are continuing to provide coverage of newly announced or recently discovered collaborations between industry, academia, and other entities to highlight the importance of such relationships in furthering medical progress and improving patient care.   

Michael J. Fox Foundation and Parkinson’s

A recent opinion article published in Nature Medicine discussed how “Money without collaboration won’t bring cures.”  The piece, written by Todd B. Sherer, chief executive officer of The Michael J. Fox Foundation for Parkinson's Research, maintained that “It's up to stakeholders at every stage of therapeutic development—industry and academic researchers, policymakers, patient foundations and even patients themselves—to embrace the power of collaboration.  Only then will we enable translational research and push much-needed treatments to the clinic faster.” 

Sherer noted that he attended the inaugural meeting of NCATS, of which he is charter member. While noting the honor of serving on the council, he asserted that “government efforts to kickstart drug development will not be enough to bridge the divide between the basic research typically conducted by academic institutions and the large-scale clinical studies orchestrated by the pharmaceutical industry.”  

Rather, he recognized that “it is the shared responsibility of all of us involved in every stage of drug development—at any phase, in the public or private sector—to contribute to filling this gap.”  Using his experience at the Michael J. Fox Foundation (MJFF), Sherer said he has seen first hand “how this approach can pay off.”    

“We’ve seen how collaborations among academic and industry players are ignited when researchers share information in real time, how meeting scientists' needs for better research tools enables them to move toward breakthroughs faster and how investing in early promising therapeutic targets is crucial.  Despite the inherent risks involved in these efforts, the reward could be the cure that countless patients don’t have the time to wait for.” 

The foundation’s “exclusive mission is to accelerate the development of a cure for Parkinson’s disease, and over 90% of [their] funding is allocated to the translational and clinical research closest or most essential to patient relevance.”  Thus far, the foundation has approximately $300 million in research to date, something Sherer called “chump change in the context of the therapeutic development ecosystem.” 

Nevertheless, he noted that due to the foundation’s “strategic investments and untraditional collaborations with industry partners,” they have “seen seismic shifts in the Parkinson's therapeutic development landscape over the past decade, with major progress toward improved symptomatic and disease-modifying therapies alike.”   

Accordingly, Sherer asserted that “Strategic investments in translation and collaboration can pay off,” and the MJFF has seen firsthand how strategic investments in translation and collaboration can pay off.  For example, a new partnership between Vanderbilt University and Bristol-Myers Squibb (BMS) leverages investments MJFF has been making in Vanderbilt since 2005. The Tennessee-based institution’s Center for Neuroscience Drug Discovery, with MJFF’s funding, has been working to develop a new glutamate-based class of symptomatic treatment for Parkinson’s disease.  Following proof of concept in rodent models, this work has now ripened to readiness for major follow-on funding from BMS. It's a win for our foundation, Vanderbilt, BMS and, most importantly, patients with Parkinson’s. 

Sherer further explained his role in the US Presidential Council of Advisors on Science and Technology (PCAST) on the need for widespread, public-private collaboration to propel innovation in drug discovery and development and to be part of a panel discussion on implementing PCAST’s recommendations.  He also noted the formation of TransCelerate BioPharma, a nonprofit organization that means to take a collaborative, precompetitive approach to accelerate the development of new drugs.  

Given these announcements Sherer was “energized by the prospect of greater resources and a new framework for collaborations focused on problem-solving in the translational space, especially when today's scientists have so many promising new avenues for investigation, new targets for therapies and rapidly advancing technologies—crucial tools for progress that the field didn't know about, or that didn't exist, ten years ago.” 

The promise of collaboration goes beyond Parkinson’s.  For example, Sherer noted how the progress enabled by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a collaborative effort among multiple groups including government, drug companies, universities and nonprofits, “has galvanized drug development for that disease in relatively few years Alzheimer’s drugmakers have taken the proactive step of pooling data from those trials in an attempt at problem-solving and increasing the odds of better future results.”  The foundation’s “own Parkinson's Progression Markers Initiative, supported by 13 pharmaceutical funding partners, has benefited from having ADNI as a scientific precedent and a successful model of collaboration.” 

The Fox Foundation executive also highlighted the critical role patients are playing, for example, through the use of MJFF’s Fox Trial Finder, an online tool that combines matches volunteers to trials on the basis of several factors (including geography, treatment history and individual preference) and allows for anonymous two-way messaging between volunteers and clinical trial teams, has exploded since its launch by our foundation in April 2012.  More than 12,000 registrants have signed up to date.  

Despite all this success, Sherer acknowledged the need for more volunteers, and greater resources to educate patients and their loved ones about the vital part that only they can play to keep research moving forward.  Ultimately, he expressed his hope that through collaboration, “we can make cures inevitable.” 

Bayer Supports Innovative Drug Discovery in Europe  

In early February of this year, Bayer Healthcare announced that it would initiate and coordinate a newly founded pan-European consortium, named European Lead Factory, which has been launched to enhance early drug discovery addressing the need for innovative drugs.  The new five-year project will create an exceptional small molecule library collection allowing drug discovery on innovative and promising targets from pharma companies and academia.  

Bayer HealthCare and six other pharmaceutical companies, all members of the European Federation of Pharmaceutical Industries and Associations (EFPIA), will collectively contribute at least 300,000 substances to the European Lead Factory initiative.  The other 6 major drugmakers include AstraZeneca, Lundbeck, Janssen, Merck KGaA, Sanofi, and UCB Pharma.  Together the companies are pooling 196 million euros ($265 million) for this new collaboration.  Bayer said it will provide about 50,000 compounds. 

Additionally, a library of estimated 200,000 compounds will be newly developed jointly by academia and Small and Medium Enterprises (SMEs) in the course of the new initiative. Together, the two libraries will form a Joint European Compound Collection consisting of up to half a million compounds that will be accessible not only to all project partners, but also to public organizations and SMEs who are invited to introduce promising new targets for pharmacological screening. Target proposals will be selected through competitive calls. Thus, drug discovery using the Joint European Compound Collection will be performed on proposed targets from pharma companies as well as targets sourced from the public domain.

The consortium will also set up a state of the art European Screening Centre with compound logistics and High Throughput Screening (HTS) facilities which will be located in Scotland and The Netherlands respectively. The highly-automated process will allow researchers to rapidly screen the exceptional Joint European Compound Collection for molecules that could be a promising starting point in the development of new drugs.

“The European Lead Factory is an outstanding example of a project in which public-private partnerships enable collaborative drug discovery”, said Hanno Wild, Senior Vice President and Head of Candidate Generation & Exploration at Bayer HealthCare Global Drug Discovery. “The platform brings together academia and industry as well as Small and Medium Enterprises in a unique partnership aiming to discover innovative medicines. Bayer is committed to further develop this novel platform by providing decades of experience in drug development. The joint efforts of the consortium will support drug discovery and hopefully generate new therapies for patients.”

“It’s a big change for companies because their compound libraries have usually been kept very secret,” said Ton Rijnders to Reuters, scientific director of Dutch non-profit group TI Pharma, who is helping to run the project.  “They are doing this because it is cheaper than building ever larger libraries on their own - and partnering with academics gives them access to innovative ideas.”

The novel consortium is a public-private partnership supported by Europe’s Innovative Medicines Initiative (IMI), the world’s largest public-private partnership in health.  The Innovative Medicines Initiative currently supports 40 projects, many of which are already producing impressive results. The projects all address major bottlenecks in drug development, and so will accelerate the development of safer and more effective treatments for patients.

Michel Goldman, IMI Executive Director, said: “IMI is very excited by the launch of the European Lead Factory. This unique project is an excellent example of how a public-private partnership can transform the way in which the pharmaceutical sector identifies new medicines. For the first time, it will give European researchers unprecedented access to industry chemical collections and facilitate the translation of their findings into actual treatments for patients. This project will not only advance the chances of success in the discovery of new medicines by European researchers, but also add value by building research capacity in Europe.”

The European Lead Factory consists of 30 international partners, including pharmaceutical companies, SMEs and academia. This new public-private partnership has been initiated for a period of five years. Based on the proven success of the open innovation model, the European Screening Centre and the teams of SMEs and academic institutions aim for a sustainable role in drug discovery and the future growth of drug development in Europe after the initial funding period.  

The total budget for the project amounts to around €196 million. Up to €80 million comes from the European Commission’s Seventh Framework Programme for Research (FP7), and about €91 million is provided as in kind contributions from the participating EFPIA companies. The remaining €25 million comes from other contributions from the non-EFPIA participants. 

Avastin Significantly Improves Survival for patients with recurrent and metastatic cervical cancer 

In addition to the recent collaboration, NIH recently announced that “Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis of a large, randomized clinical trial.” 

It is estimated that over 12,000 women will be diagnosed with cervical cancer in the United States in 2013 and over 4,000 women will die of the disease.

The clinical trial, known as GOG240, was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the Gynecological Oncology Group (GOG).  Genentech, Inc., South San Francisco, Calif., the drug manufacturer, provided support for the trial under the Cooperative Research and Development Agreement (CRADA) with NCI for the clinical development of bevacizumab.  

The data safety monitoring committee overseeing the trial recommended that the results of a recent interim analysis be made public because the study had met its primary endpoint of demonstrating improved overall survival in patients who received bevacizumab, which also means that it delayed the chance of dying from the disease.  

Patients who received bevacizumab got a dose of 15 milligrams per kilogram (mg/kg) of body weight administered in the vein with their chemotherapy treatment and continued with this dose one day every three weeks until disease progression or unacceptable toxicity occurred.  Those patients lived a median 3.7 months longer than those who did not receive bevacizumab. Patients treated with chemotherapy alone had a median survival of 13.3 months while those who received chemotherapy and bevacizumab had a median survival of 17 months. This survival difference was highly statistically significant. However, patients receiving bevacizumab experienced more side effects than those who did not. These side effects were consistent with side effects previously known to be associated with bevacizumab. 

“The findings in this clinical trial are important because they are likely to change clinical practice and provide an opportunity to improve outcome in patients with recurrent cervical cancer who have previously had very limited treatment options,” said GOG study chair Krishnansu S. Tewari, M.D. 

“This is welcome news as progress has been very difficult against this cancer, and GOG physicians and patients who participated have made an important contribution,” said Jeff Abrams, M.D., clinical director of NCI’s Division of Cancer Treatment and Diagnosis.  Full data has been submitted to the American Society of Clinical Oncology 2013 Annual Meeting. The trial is GOG240, Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab for Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer, clinical trial registry number NCT00803062. 

NCATS Calls for Regulatory Partners to Develop, Market Potential Rare Disease Treatment  

The National Center for Advancing Translational Sciences (NCATS), the newest addition to the National Institute of Health (NIH), recently announced in the Federal Register that in combination with NIH’s National Human Genome Research Institute (NHGRI), it is seeking out a partner to, “collaborate in the final stages of lead optimization, evaluation and preclinical development”of two new therapies; one for Gaucher disease and the other for the treatment of heart failure and fibrosis, reported RAPS. 

According to the article in RAPS, NCATS believes that a novel selective series of non-inhibitory chaperones of glucocerebrosidase (GCase) will be useful in treating Gaucher disease and other related diseases.  “Gaucher is a rare disease affecting just a few thousand people in the US, and is most commonly found in those in Ashkenazi Jews, most of whom hail from Eastern and Central Europe.” 

The disease is marked by a lack of the GCase enzyme, which causes substances to build up in the body's organs.  The severity of the disease depends on which of three types is inherited by the patient, but the disease is often fatal.  “NIH said it hopes its GCase chaperones will be able to guide the enzymes to lysomes after synthesis in the ribosome instead of accumulating in the endoplasmic reticulum.  This is more difficult than it seems, NIH wrote in its Federal Register announcement.” 

“The main challenge in the development of molecular chaperones for Gaucher disease is that chaperones are inhibitors of the enzyme. This complicates their clinical development, because it is difficult to generate an appropriate in vivo exposure at which a compound exhibits chaperone activity, but does not inhibit the enzyme's function.” 

“The good news, it said, is that high throughput screening has identified several small-molecules that do not inhibit the enzyme.”  “These lead molecules were found to increase the specific activity of the enzyme, promote the translocation of GCase to the lysosome in Gaucher fibroblasts and macrophages, reduce the accumulated substrate, and restore efferocytosis of these cells.”  NIH added that the compound could also come to be used as a treatment for Parkinson’s disease, which exhibits some genetic parallels with Gaucher disease, or more generally to “enhance the efficacy of enzyme replacement therapy.” 

Then, NCATS referenced recombinant relaxin hormone, which NIH said is already in Phase III trials for the treatment of acute heart failure.  Researchers wrote that the compound is “difficult to study in chronic settings due to the short half-life and the need for intravenous administration of the recombinant hormone.”  A new, recombinant version of the hormone—the likes of which NCATS has been studying—would hypothetically “have numerous benefits and will allow investigating additional therapeutic applications where chronic administration is required.” 

“As with the GCase Chaperones, NCATS said it has successfully identified a series of small-molecule agonists that it said are ‘potent, highly selective, easy to synthesize, and with reasonable metabolic and physical properties’ that display ‘similar efficacy as the natural hormone in several functional assays.’” 

“If successfully marketed, the product could mean big money for its sponsor.  Heart failure—the disease which NCATS thinks this product would be most successful at treating—affects millions of Americans and is understood by the American Heart Journal to be the leading cause of hospitalizations for those over the age of 65.” 

RAPS noted that these announcements from NCATS were somewhat unusual because it was “looking for a partner that already has a sense of the regulatory challenges ahead of it.”  They noted that the Cooperative Research and Development Agreement (CRADA) “scope will also include studies beyond candidate selection including all aspects of pre-clinical studies such as toxicity studies and chemistry good manufacturing practice (GMP) scale up of select compound(s) and manufacture of controls leading to a successful investigational new drug (IND) application.”  

While NIH routinely licenses technology to outside groups, it does so “usually without the preconditions that it be able to bring a drug to market using the technology or their history as a company.” 

“Not so with its CRADA,” RAPS wrote.  "”Collaborators should have experience in the pre-clinical development of small molecules and a track record of successful submission of IND applications to the FDA for rare and neglected diseases,” NCATS added.  The agency said it hopes the compound can be “expeditiously commercialized and brought to practical use.” 

“Though the compounds are still relatively early in the development cycle—NIH notes that it’s only undergone early-stage in vivo and in vitro testing to determine absorption, distribution, metabolism and elimination (ADME) and activity studies on human macrophages—it still represents a potential new pipeline for patients suffering from rare or neglected diseases, as well as a potential source of profit for companies whose own pipelines have been notoriously stagnant in recent years.”

AMA to Support Educational Grants to Transform Medical Schools

The American Medical Association (AMA) recently announced a $10 million competitive grant initiative to attract bold, innovative projects to transform the way medical schools train future physicians.  

“Rapid changes in health care require a transformation in the way we train future physicians,” said AMA President Jeremy A. Lazarus, M.D. “The AMA is deeply committed to redesigning undergraduate medical education to prepare the medical students of today for the health care of tomorrow.” 

Across the continuum of medical education, the gap between how physicians are trained and the future needs of health care continues to widen.  The AMA is seeking to attract and support bold, rigorously evaluated innovations that align medical student training with the evolving needs of patients, communities and the changing health care environment. 

As part of the “Accelerating Change in Medical Education” initiative, the AMA will provide $10 million over the next five years to fund 8-10 projects that support a significant redesign of undergraduate medical education.  Interested medical schools must submit brief proposal ideas by February 15.  Specifically, funding will be awarded to medical schools for: 

• Developing new methods for teaching and/or assessing key competencies for medical students and fostering methods to create more flexible, individualized learning plans.
• Promoting exemplary methods to achieve patient safety, performance improvement and patient-centered team based care, and improving understanding of the health care system and health care financing in medical training.
• Enhancing development of professionalism throughout the medical education learning environment. 

“In keeping with the AMA’s historic leadership in all levels of physician education, we are excited to continue our work to improve medical education for patients and physicians,” said Dr. Lazarus.  “We hope to find and support proposals to develop innovative new education models that can be duplicated in medical schools across the country.” 

From the initial pool of proposals, the AMA will invite a select group of medical schools to submit a full proposal by May 15 and will conduct a thorough review of all materials before announcing the selected schools at its Annual meeting in June 2013.

Among its criteria, the AMA says it is looking for proposals that create “more flexible, individualized learning plans,” or that promote “exemplary methods to achieve patient safety, performance improvement and patient-centered team based care.”

More Industry Academic Alliances

We recently covered Twenty Industry-Academic Alliances in 2012.  In the past, we have also written extensively about other physician-industry and academic-industry collaborations.  After running our recent story, we came across several other alliances, discussed in further detail below, and will continue to cover such collaborations as they occur.   

GlaxoSmithKline and University of Texas, MD Anderson Cancer Center

GlaxoSmithKline (GSK) recently announced that it has gained rights to a preclinical program from the renowned MD Anderson Cancer Center, in a pact focused on antibodies that trigger immune attacks against cancer.  It’s the first major pharma deal for the center's Institute for Applied Cancer Science (IACS), which was set up last year to operate as a translational research unit that is akin to “a biotech embedded” in an academic setting, a spokesman for the center said in an email.

The prized antibodies in the deal act on OX40 receptors on T cells, helping the ninjas of the immune system recognize tumor cells as enemies in need of an ass kicking.  Like all preclinical programs, the merits of the therapies must pass some initial tests before they advance to human clinical studies.  MD Anderson’s immune-triggering antibodies emerged from the research of Yong-Jun Liu, M.D., Ph.D., and colleagues when he was professor and chair of MD Anderson's Department of Immunology.  He’s since moved on to become the chief scientist of the Baylor Research Institute in Dallas.

Malignant cells are an abnormality that usually attracts a response from the body’s immune system, yet cancer often survives by evading or thwarting anti-tumor immunity.  Consistently unleashing the power of the immune system against cancer would be a major step forward for cancer patients.

T cells are lymphocytes, a type of white blood cell produced by the thymus, equipped with receptors that recognize and bind to antigens, which may include abnormal cells.  “T cell recognition of a tumor antigen is not enough to activate the T cells against cancer cells, they need a secondary signal to tell them 'that antigen you have is a bad thing, you have to attack,’” said Liu.

OX40 is one of these secondary or co-stimulatory receptor proteins. Liu and colleagues found that when it’s activated, it enhances immune attack and blocks suppressors of immune response.  Liu and his MD Anderson colleagues generated and screened hundreds of antibodies that could potentially act as on switches for OX40 by mimicking its natural activator, OX40L, a molecule that binds to OX40. Years of research narrowed the candidates to a handful of activators, or agonists, which were tested in mice and then altered for human use.  Initial clinical trials will occur only after necessary preclinical drug development conducted under the agreement succeeds.

 “This agreement is not only a tribute to the ability of MD Anderson scientists to discover new targets and potential therapies against those targets for cancer patients, it's also a testament to the vision shared by GSK and MD Anderson that successful clinical development of oncology drugs requires seamless integration of drug development expertise and deep biological knowledge,” said Giulio Draetta, M.D., Ph.D., IACS director. “The IACS was formed to enable precisely such integration to expedite the accurate translation of great science into drugs.”

The overall potential value of the agreement to MD Anderson over the life of the agreement is estimated at more than $335 million. Under the terms of the agreement, MD Anderson will receive an upfront license payment and funding for IACS research collaboration activities, as well as payments for reaching development, regulatory and commercial milestones.  In addition, MD Anderson will also be entitled to royalties deriving from the commercial sales of products developed under the collaboration.

“We’re excited about this opportunity with GSK to improve cancer treatment,” Draetta said. “The IACS is a drug development engine with industry-seasoned scientists embedded in a comprehensive cancer center, and as such is ideally suited for this type of collaboration.”

The institute is a vital platform resource for MD Anderson’s recently announced and unprecedented Moon Shots Program, which focuses resources and diverse expertise to significantly reduce mortality in the short term and promote cures long term, beginning with eight inaugural cancers.  “It’s gratifying to see MD Anderson and GSK take this important step towards translating a basic science discovery into a potential new therapy that can proceed to clinical trial,” Liu said.

StemBANCC 

Roche and the Innovative Medicines Initiative (IMI) launched StemBANCC, a new academic–industry partnership that unites ten (10) pharmaceutical companies and 23 academic institutions. Initiated and coordinated by Roche and managed by Oxford University, StemBANCC aims to use human induced pluripotent stem cells as research tools for drug discovery with the goal of using this new technology to develop human disease models and enhance drug development. 

“The aim of StemBANCC is to generate and characterize 1,500 high quality human induced pluripotent stem cell lines derived from 500 patients that can be used by researchers to study a range of diseases including diabetes and dementia,” explained Martin Graf, head of the stem cell platform and coordinator of the project.  “The cell lines will help implement patient models that will facilitate the drug development process thanks to the possibility of reproducing the disease mechanism in vitro.”  The ten companies include: 

• F. Hoffmann-La Roche Ltd, Basel, Switzerland
• Abbott GmbH & Co KG, Wiesbaden-Delkenheim, Germany
• Boehringer Ingelheim International GmbH, Ingelheim, Germany
• Eli Lilly, Hampshire, United Kingdom
• Janssen Pharmaceutica NV, Beerse, Belgium
• Merck KGaA, Darmstadt, Germany
• Novo Nordisk A/S, Bagsværd, Denmark
• Orion Corporation, Espoo, Finland
• Pfizer Limited, Sandwich, UK
• Sanofi-Aventis Research and Development, Chilly-Mazarin, France 

The StemBANCC project will focus on peripheral nervous system disorders (especially pain), central nervous system disorders (dementias), neurodysfunctional diseases (migraine, autism, schizophrenia, and bipolar disorder), and diabetes. The project will also investigate the use of human induced pluripotent stem cells for identifying drug targets and biomarkers, screening potential drug treatments, and toxicology testing. 

The research resulting in the creation of the first induced pluripotent stem cells was a major scientific advance by scientists John Gurdon (Cambridge University) and Shinya Yamanaka (Kyoto University) who were awarded the 2012 Nobel Prize in Physiology or Medicine.  Most adult cells can only divide to produce other cells of the same type.  For example, skin cells can only make other skin cells, and liver cells can only make other liver cells.

However, in recent years researchers have developed a way of reprogramming ordinary adult cells to create stem cells that can be used to generate any kind of cell.  These induced pluripotent stem cells offer a supply of different kinds of human cell such as cardiomyocytes, endothelial cells, or neurons that can be used for a broad range of in vitro tests in research and early-stage drug development. 

Because these cell lines are derived directly from real patients, they include the genes that may be implicated in diseases of interest.  Moreover, such cell lines have the advantage of being developed from samples that have been obtained from accurately screened and defined groups of patients.  Having a solid database with numerous patients and accurate data on their disease is expected to enable a new level of insight into the disease mechanisms. 

Roche scientists recognized the potential of induced pluripotent stem cells more than three years ago.  Since then they have worked with partners at Harvard University, Massachusetts General Hospital, and Boston Children’s Hospital to create over 100 human induced pluripotent stem cell lines that can be used to model cardiovascular and neurological diseases. 

According to ReportsnReports.com, induced pluripotent stem cells (iPSCs) are now sold by 53.4% of U.S. research product companies and 38.7% of research product companies worldwide. Annual growth in the number of iPSC research products sold worldwide is growing at a rate of 14.7% per year.  In addition, 22% of all stem cell researchers now report having using iPSCs within a research project.  The 23 universities research organisations, public bodies, non-profit groups include: 

• University of Oxford, Oxford, UK
• Charité - Universitätsmedizin Berlin, Berlin, Germany
• Hebrew University of Jerusalem, Jerusalem, Israel
• Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH). Neuherberg, Germany
• Institut National de la Santé et de la Recherche Médicale, Paris, France
• King’s College London, London, UK
• Linkopings Universitet, Linköping, Sweden
• Medical Research Council UK, Swindon, UK
• Medizinische Hochschule Hannover, Hannover, Germany
• Medizinische Universität Innsbruck, Innsbruck, Austria
• Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Reutlingen, Germany
• Region Hovedstaden - Capital Region of Denmark, Hillerød, Denmark
• Tel Aviv University, Tel Aviv, Israel
• Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
• Université de Genève, Geneva, Switzerland
• Université de Lausanne, Lausanne, Switzerland
• Université de Technologie de Compiègne, Compiègne, France
• University College London, London, UK
• University of Birmingham, Birmingham, UK
• University of Cambridge, Cambridge, UK
• University of Edinburgh, Edinburgh, UK
• University of Lübeck, Lübeck, Germany
• University of Newcastle upon Tyne, Newcastle upon Tyne, UK 

Joslin Diabetes Center and Sanofi 

In addition, last spring, Joslin Diabetes Cente,r a teaching and research affiliate of Harvard Medical School, and Sanofi Aventis, announced a new collaboration to promote the development of new medicines for the treatment of diabetes and related disorders.  The collaboration was unveiled at the 2012 Bio International Convention in Boston, Mass. by Dr. Elias Zerhouni, President of Global R&D of Sanofi.  This broad alliance between Joslin and Sanofi spans four significant R&D areas of diabetes and complications aimed at new drug discovery and advancing treatment effectiveness in patients.  

Building on Joslin’s experience in diabetes research and care, the collaboration will focus on four key areas within diabetes and related metabolic disorders to identify potential new biologics or small drug candidates for the treatment of late complications of diabetes and new insulin analogs with more targeted efficacy.  Additionally, research will address the challenges of insulin resistance and personalized medicine, with the overall aim of improving the lives of people living with diabetes. 

Dr. Elias Zerhouni , President, Global R&D, Sanofi, commented: "This collaboration brings together two important forces in diabetes therapy – Sanofi Diabetes and Joslin Diabetes Center – which have the potential to define new pathways towards better understanding the nature of this disease and developing new treatments. This collaboration further demonstrates Sanofi's commitment to improving diabetes management and care through the development of innovative research strategies."

Under the terms of the agreement, Sanofi has options to commercialize the results of the research.  Both parties will have access to intellectual property for internal research use. 

C. Ronald Kahn , M.D., Mary K. Iacocca Professor of Medicine at Harvard Medical School and Chief Academic Officer of Joslin Diabetes Center, who will head the alliance team, added: "This opportunity brings together experts from the pharmaceutical industry with our team of scientists and clinicians, who are devoted to research and clinical care for diabetes and related metabolic disorders. The result should be a very exciting collaboration with great potential for innovative research that will participate to advance diabetes treatment and patient care."

University COI Policies and Generic Drugs – The Old Becomes New

A recent study from the Perelman School of Medicine at the University of Pennsylvania revealed that psychiatrists who were exposed to conflict of interest (COI) policies during their residency were less likely than peers who lack similar training to prescribe brand-name antidepressants, “which are heavily promoted to psychiatrists and tend to be more expensive,” the study claims.  The study claimed that a “dramatic increase in prescription drug use,” and relationships between pharmaceutical representatives and physicians have “come under extensive scrutiny both within the medical profession and by policy makers.”

“Our study clearly shows that implementation of COI policies have helped shield physicians from the often persuasive aspects of pharmaceutical promotion,” first author Andrew Epstein stated in the press release.  The results will be published in the February issue of Medical Care.  Some have speculated that if the results are correct, we may begin to see an even stronger increase and flurry of COI policies at academic medical centers, although most already have strong policies in place. 

What may change, however, is the emphasis that certain professors or programs place on teaching and training young physicians on COI policies.  This will be troublesome in some cases where the instructor has a negative view of industry and discourages industry relationships or collaboration—which may lead to a generation of physicians who do not work with industry.  We have previously reported that physicians who refuse to see pharmaceutical sales reps were less likely to be aware of important risk information and new clinical data.

The study focused on antidepressants because “they have been among the most heavily marketed drug classes,” Epstein said.  “Data show that antidepressant use increased nearly 400 percent from 1988 to 2008.  The goal for this study was to determine whether exposure to COI policies during residency would influence psychiatrists' antidepressant prescribing patterns after graduation.”

Penn Medicine in 2006 implemented policies placing restrictions on physician interactions with pharmaceutical representatives.  In 2008, the Association of American Medical Colleges (AAMC) developed COI policy guidelines for gifts, free meals, and medication samples provided by pharmaceutical representatives to physicians and trainees.  “The concern was that these interactions could influence clinicians to prescribe brand medications even if they were more expensive or less suitable for patients than generic alternatives.”

To assess the effects of COI policies on physicians’ prescribing patterns after residency, the research team examined 2009 prescribing data from IMS Health for 1,652 psychiatrists from 162 residency programs.  The physicians fell into two categories: about half graduated residency in 2001, before COI training guidelines were implemented, while the other half graduated residency in 2008, after many medical centers adopted COI policies.

Physicians were also categorized based on the restrictiveness of the COI policies adopted by their residency programs' medical centers.  Results of the study show that, although rates of prescribing brand antidepressants, including those that were heavily promoted and brand reformulations, were lower among 2008 graduates than 2001 graduates in general, the rates were lowest for 2008 graduates of residency programs with very restrictive COI policies.  Such results are hardly surprising given the fact that academic medical centers with very restrictive COI policies likely restrict almost all access by industry on their campuses and strictly limit any kind of off-campus interactions with industry—making it almost impossible for the 2008 graduates to ever learn about brand-name drugs. 

Another factor that the study might not have taken into consideration is that a number of the antidepressants likely went off-patent during this time frame so that pharmacies would have had to fill a brand-name prescription with a generic regardless, unless the physician specifically instructed otherwise. 

Additionally, the study did not attempt to measure patient or clinical outcomes.  In other words, there was no discussion or evidence that patients being prescribed brand-name drugs did worse than those on generics or had any more adverse consequences.  Moreover, as the study recognized, there can easily be many other differences and factors between two groups that are 7 years apart—e.g., increased medical literature; advances in research and clinical data; postmarket safety reports; changed, revised or new guidelines, and so on.

Part of the motivation behind the study, as Epstein recognizes, is the high cost of brand-name medications and anti-depressants, particularly because patients must take these pills multiple times a day, for long periods of time—years, even decades.  Accordingly, the study may be seen by some as an argument to help reduce healthcare costs.  Yet Epstein cautioned that lower costs achieved through stringent COI policies may come at a price. 

“Contact with the pharmaceutical industry may have important informational benefits for physicians.  And, by exposing trainees to industry representatives, we may be helping them prepare to navigate these relationships after graduation,” said Epstein. “Nevertheless, while these relationships may be useful in some ways, our study clearly shows that implementation of COI policies have helped shield physicians from the often persuasive aspects of pharmaceutical promotion.” 

Epstein notes that in future research it will be critical to assess whether these policies have similar effects on other drug classes and physician specialties. 

Conclusion

As we have mentioned before, educating young physicians and physicians in training about COI policies and interactions with industry and pharmaceutical sales representatives is a noble goal and one that should be taken seriously.  However, allowing those faculty and medical school staff who are already critical of industry and have their own personal biases about industry to educate impressionable minds is problematic.  There needs to be balance when educating medical students and residents about COI policies and relationships with industry.  There must be an equal voice for industry so that students can understand the critical and crucial relationships that physician-industry collaboration brings to medical innovation and progress.  

If future research is to be conducted on COI policies, such research should evaluate the extent to which such policies adversely affect physician industry relationships, and how such adversity can harm patient care and decrease good patient outcomes.  Moreover, schools with COI policies must ensure that those responsible for training and educating students about COI policies give a fair and balanced presentation of industry relationships.