Life Science Compliance Update

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30 posts from May 2013

May 31, 2013

FDA Five Year Plan on Risk Benefits Framework

Five Year Plan
The Food and Drug Administration (FDA) recently announced the availability of a draft 5-year plan describing the Agency’s approach to further developing and implementing a structured framework for benefit-risk assessment in the human drug and biologic review process and the opportunity for public comment on the draft plan.  This plan is part of FDA’s commitments that were made as part of the fifth authorization of the Prescription Drug User Fee Act (PDUFA V), which was included in the Food and Drug Administration Safety and Innovation Act (FDASIA).


Section 905 of FDASIA amends section 505(d) of the Federal Food, Drug, and Cosmetic Act (FDCA) by requiring FDA to “implement a structured risk-benefit assessment framework in the new drug approval process to facilitate the balanced consideration of benefits and risks, a consistent and systematic approach to the discussion and regulatory decision making, and the communication of the benefits and risks of new drugs.”   Title I of FDASIA reauthorizes PDUFA and provides FDA with the user fee resources necessary to maintain an efficient review process for human drug and biological products.  The reauthorization of PDUFA includes performance goals and procedures for the Agency that represent FDA’s commitments during fiscal years 2013-2017.

Section X of the PDUFA Goals Document, titled “Enhancing Benefit-Risk Assessment in Regulatory Decisionmaking,” addresses the development of a 5-year plan that describes the Agency’s approach to further develop and implement a structured benefit-risk framework in its human drug and biologic review process.  The publication and implementation of this plan are intended to fulfill the requirement in section 905 of FDASIA and the commitments described in Section X of the PDUFA Goals Document.

Ensuring the safety, effectiveness, and quality of human drugs is a complicated regulatory task, requiring FDA’s consideration of a multitude of complex factors.  FDA’s regulatory decision making process takes into consideration not only the data submitted in a marketing application, but also a broad set of additional factors, including the clinical context for the proposed product (such as the nature and severity of the disease or condition that the proposed product is intended to treat or prevent and the benefits and risks of other available therapies for that disease or condition) and any risk management tools that might be necessary to ensure that the benefits of the proposed product outweigh its risks.

“FDA believes that implementing a standardized structure for the analysis of the various benefit and risk considerations that make up a regulatory decision will help to facilitate balanced and consistent consideration of the benefit and risk factors during the review process and to enhance the transparency of regulatory review.”  FDA therefore developed the draft plan describing a “benefit-risk assessment framework that is designed to make explicit the consideration of the various benefit-risk factors and the role of those factors in the regulatory decision-making process for human drug and biological product marketing applications.”  It is important to note that, as specified in section 905 of FDASIA, this framework does not change the criteria for approval of a drug or biological product.  All new drug applications and biological license applications must meet the requirements for approval under the FD&C Act and the Public Health Service Act, respectively.

By clearly articulating FDA’s key considerations in a standard structure, this framework can serve as an important tool for the analysis and discussion of the relevant benefit and risk considerations during the review process.  

A second and equally important purpose of the benefit-risk framework is that it can serve as a tool to communicate the reasoning of FDA's regulatory decisions to the public.  When FDA approves a new drug or biological product, it generally posts decisional memos on the Agency’s Web site.  These documents may be highly technical and may not be easily understandable to a broad audience with varying backgrounds. The benefit-risk framework aims to enhance FDA’s communication of its decisions by making clear the important considerations in the Agency's decision-making process, and how they affected the final regulatory decision, in a clear, succinct summary.

Draft Plan

From an analysis of prior regulatory decisions, FDA developed a basic structure of a benefit-risk framework that includes the following categorization of key decision factors:

Analysis of Condition and Current Treatment Options provide a summary and assessment of the severity of the condition that the product is intended to treat and other therapies available to treat the condition.  This represents the context of the decision that can provide useful information for weighing the benefits and risks of the drug under review

Benefit and Risk provide a summary and assessment of the submitted evidence concerning the drug under review.  Key considerations of benefit include the results of the clinical trials and the clinical meaning of primary and secondary endpoints, as well as appropriate analyses of subpopulations.

Key considerations of risk include the adequacy of the safety database, the severity and reversibility of adverse events, and the potential for sub-optimal management in the post-market setting that may be of concern.  In assessing benefit and risk, consideration is also given to other factors that may be relevant for a particular drug review, including nonclinical pharmacology and toxicology data; clinical pharmacology (e.g., mechanism of action, pharmacodynamics, and pharmacokinetics); chemistry, manufacturing, and controls (CMC); and clinical microbiology.

Risk Management provides a summary and assessment of any efforts that could help to mitigate the identified safety concerns, or ensure that the drug is directed to those patients for whom the risk is considered acceptable.

Within each of these factors, there are two considerations that inform the regulatory decision.  The first consideration consists of identifying facts as well as uncertainties and any assumptions that need to be made to deal with what is not known.  The second consideration consists of the conclusions that must be made about each decision factor. These conclusions are the subjective interpretation of the evidence for each aspect of the benefit-risk assessment.  FDA terms these two categories as Evidence and Uncertainties and Conclusions and Reasons, where:

Evidence and Uncertainties presents the facts, uncertainties, and any assumptions made to address these uncertainties that contribute to the assessment of benefit and risk.

Conclusions and Reasons captures the implications of the facts, uncertainties, and assumptions with respect to regulatory decision-making, drawing conclusions from the evidence and uncertainties and explaining the bases for those conclusions.

The first two decision factors, Analysis of Condition and Current Treatment Options, represent the framework’s therapeutic area considerations and are distinct from the other drug-specific considerations in the framework.  The therapeutic area information represents the current state of knowledge regarding the condition and the available therapies and can be completed for any disease area.  As the available therapies for a disease area change or as knowledge and understanding of the disease improves, this information can be updated.

The additional factors of Benefit, Risk, and Risk Management represent the product-specific area of the framework.  The information found here relates specifically to the drug under review.  As our knowledge of a drug’s benefits and risks changes post-approval, this information can be updated in the framework, reflecting the dynamic nature of benefit-risk assessment during the drug lifecycle.

The final part of the framework is the Benefit-Risk Summary Assessment, a succinct well-reasoned summary that clearly explains FDA’s rationale for the regulatory action including important clinical judgments that contributed to the decision.  The summary should integrate the analyses of benefit and risk and the applicable statutory and regulatory standards into a coherent explanation of the conclusions reached.

The assessment draws on the key supporting evidence and uncertainties, accounts for the understanding of the condition, and considers the available therapies that establish

the context in which benefits and risks are weighed.  It also includes the rationale to support the labeling and other risk management as well as post-marketing requirements/commitments if more information is necessary to further characterize the benefits or risks of the drug.  Where there are differences of opinion within a review team with respect to scientific or clinical judgment, they are noted in the assessment along with an explanation of how the differences were resolved or taken into account in the final decision.

Characterization of Uncertainties in Benefits and Risks

Although drug regulatory decisions are informed by an extensive body of evidence on the safety and efficacy of a proposed product, in many cases, FDA must draw conclusions from imperfect data.  Therefore, identifying and evaluating sources of uncertainty (e.g., absence of information, conflicting findings, marginal results) is an important part of reviewers' work, and FDA acknowledged the role of uncertainty in the benefit-risk framework.  However, drawing conclusions in the face of uncertainty can be a complex and challenging task.

Furthermore, being explicit about the impact of uncertainty on decision-making is an important part of communicating regulatory decisions.  An approach that allows for more systematic accounting of the various sources of uncertainty and the role of uncertainty in decision-making can facilitate the characterization, integration, and communication of this information in drug review.  There are two areas where FDA intends to focus efforts beginning in FY 2013.  

The first is characterizing the uncertainty in how well the benefit-risk assessment based on pre-market clinical trial data translates to the post-market setting after the drug is approved and used in a much wider patient population.  Clinical trials are designed to demonstrate a benefit of a drug compared to some comparator, such as placebo or another drug.  During those trials, certain patients may be excluded to improve the ability to detect a benefit that can be attributed to the drug, or they may be excluded because of a potential safety concern.

However, a clinical trial population with these exclusions may not be representative of the broader patient population that will ultimately take the drug in the postmarket setting. Examples of potential differences include trial exclusions of patients on concomitant therapies, patients with other chronic conditions, or patients over a certain age. In other cases, the duration of the clinical trials may be different from the expected duration of use (e.g., antihypertensive drugs and antidiabetic drugs used chronically) or the quality and extent of patient monitoring may not be as rigorous in the post-approval setting as in the clinical trial (e.g., anticoagulants).  Being clear about such differences, understanding their impact on decision-making, and adequately communicating these sources of uncertainty are very important.

The second area pertains to FDA’s level of uncertainty about a result or finding, particularly a new finding that becomes available in the post-market setting where the basis for the finding comes from sources of varying levels of rigor. In contrast to the prospective and highly planned studies of effectiveness, safety findings emerge from a wide range of sources, including spontaneous adverse event reports, epidemiology studies, meta-analyses of controlled trials, or in some cases from randomized, controlled trials.  However, even controlled trials, where the evidence of an effect is generally most persuasive, can sometimes provide contradictory and inconsistent findings on safety as the analyses are in many cases not planned and often reflect multiple testing.  A systematic approach that specifies the sources of evidence, the strength of each piece of evidence, and draws conclusions that explain how the uncertainty weighed on the decision, can lead to more explicit communication of regulatory decisions.  FDA anticipates that this work will continue beyond FY 2013.

Implementation and Meetings

FDA plans to use a staged approach in implementing the benefit-risk framework in human drug review.  This allows opportunity for continued refinement of the framework and its integration into the human  drug review process before further expansion into additional types of applications.

During FY 2014 and 2015, FDA plans to implement the framework in the review of NME NDAs and original BLAs.  As the benefit-risk assessment is revisited in the post-market setting based on new information for these applications, review teams analyzing the safety issue will be expected to update the benefit-risk framework with the analysis conducted, including any regulatory action resulting from that work, as appropriate. Following implementation in NME NDAs and original BLAs, FDA intends to implement the framework in efficacy supplements for new/expanded indications in FY 2016 and all original NDAs in FY 2017.

Following integration of the benefit-risk framework with the CDER and CBER clinical review templates and summary memoranda templates, training will be offered to reviewers and decision-makers in the use of these materials.  Such training may entail face-to-face (just-in-time) training for the reviewers and decision-makers who will be expected to implement the framework, as well as an introduction to the benefit-risk framework as part of CDER and CBER’s New Reviewer Training.

Both Centers will also revise current procedural documents for staff and decision-makers that include revision of the Manual for Policies and Procedures that governs CDER’s clinical review template and associated appendices as well as the Standard Operating Practices and Procedures document that governs CBER’s clinical review template.

Current clinical reviews can be rather lengthy, highly detailed documents. Distilling such an extensive document down to a short and concise summary can be challenging and may also highlight the need for an additional type of training.  Over time, CDER and CBER will build a database of worked examples of benefit-risk frameworks that can be used as a reference for reviewers.  Such a database can serve a dual purpose of providing examples of high quality frameworks as well as establishing an easily accessible set of regulatory precedents that can be a future reference when similar regulatory decisions must be made.

Following implementation of the benefit-risk framework in the drug review process, FDA intends to publish the completed frameworks for newly approved products on its website, to the extent that FDA is permitted to release the information under applicable disclosure laws.  By the end of FY 2014, FDA anticipates posting benefit-risk frameworks of approved products following the regulatory action. Over this same time period, FDA also anticipates integrating the benefit-risk framework as part of Advisory Committee background packages to quickly orient the committee to the important review issues in the application under discussion.

Change Control Board

Consistent with CDER and CBER’s approach to continuous improvement, inevitably there will be a need to periodically review and modify the benefit-risk framework as well as the review templates and decision memoranda in each Center.  These revisions could result from increased reviewer experience with the framework, feedback from Center management related to increasing the utility of the framework, and feedback from public stakeholders related to the framework’s ability to communicate FDA’s rationale for regulatory decisions.

Because CDER and CBER are responsible for the regulation of different types of products, each Center plans to establish a Change Control Board (CCB) that will be responsible for analyzing feedback and input on the benefit-risk framework from their respective review staffs and making recommendations for enhancements to the framework and the clinical review templates for each Center.  Although each Center will maintain some autonomy in terms of their respective clinical review templates, the CDER and CBER CCBs will ensure close coordination across the Centers on the harmonization of the benefit-risk framework structure as well as implementation of the framework in the review of human drugs and biological products.

A key source of feedback regarding recommended modifications to the benefit-risk framework will come from the review staff who use it during their review work. Accordingly, the CCBs in CDER and CBER will be composed of primary clinical review staff as well as review management from the Office of New Drugs in CDER or the review offices (Blood, Vaccines, and Cellular, Tissue, and Gene Therapies) in CBER, as appropriate.  Because of the risk and risk management considerations in the framework, representation is also expected from CDER’s Office of Surveillance and Epidemiology on the CDER CCB and from CBER’s Office of Biostatistics and Epidemiology on the CBER CCB.

Each Center also intends to maintain an internal Benefit-Risk Advisory Group that will serve three purposes: (1) to provide overall direction in implementing structured benefit-risk assessment in the drug and biological product review process in each Center, (2) to evaluate finished benefit-risk frameworks and other work products to ensure consistent and high-quality representation of CDER and CBER decision-making before publication, and (3) to review and approve proposed modifications to the benefit-risk framework and the clinical review template that are recommended by the respective CCBs.

The CDER and CBER Advisory Groups will ensure close coordination across the Centers regarding the harmonization of the benefit-risk framework structure as well as implementation of the framework in the review of human drugs and biological products.

Public Meetings

As part of enhancing benefit-risk assessment in PDUFA V, FDA has committed to holding two public workshops on benefit-risk considerations from the regulator’s perspective.  The first workshop, slated to be held in early FY 2014, is expected to focus on the various frameworks and methods available and their appropriate application to drug regulatory decision-making.  FDA anticipates that this workshop will include participation of other drug regulatory authorities who are also implementing benefit-risk frameworks in their drug decision processes.  This discussion will examine the ability of frameworks to make explicit the benefit and risk considerations and associated uncertainties and assumptions that are part of drug regulatory decision-making.

The second workshop is expected to focus on the results of implementing frameworks at regulatory agencies both in pre-market application review as well as post-market safety review.  This meeting will be an opportunity to share any challenges and lessons learned in applying a more structured approach to regulatory decision-making. As implementation progresses in PDUFA V, further detail regarding FDA’s plan for this workshop will be included in an update to this document.

Evaluation of the Benefit-Risk Framework

The PDUFA V Commitments also require that this draft five-year plan include a plan to evaluate the impact of the benefit-risk framework in the human drug review process. The specifics of FDA’s implementation approach are still evolving as review staff acquire experience and provide feedback on the framework and its implementation in drug review.  In addition, comments received on this draft plan from the public may suggest alternatives to FDA’s approach.

Furthermore, as FDA integrates the framework concepts into it’s clinical review template during FY 2013, FDA expects that this experience will lead to best practices that will be applied to implementation of the framework in FY 2014.  At that time, a more informed evaluation of the impact of the benefit-risk framework can be specified.  FDA anticipates that this evaluation will consider the utility of the framework in communicating key benefit and risk considerations both internally and externally, facilitating decision-making including decisions about risk management, and training new review staff.

Some of the evaluation questions FDA expects to examine include (1) whether the framework provides a clearer explanation of FDA approval decisions to public stakeholders, including patients, consumers, healthcare professionals, and industry; (2) whether the framework provides value to internal reviewer communications and discussions related to premarket regulatory decisions; and (3) whether the framework provides value in supporting consideration of emerging safety and efficacy information in post-market drug decision contexts. Given the implementation timetable described in Section 4, FDA expects that the evaluation will begin in FY 2015-2016 after full implementation has occurred in a sufficient number of application reviews.  More information regarding the evaluation will be included in an update to the draft plan.

May 30, 2013

HITECH Strategies for Data Sharing, Goals for 2013

Since enactment of the Health Information Technology for Clinical and Economic Health Act (HITECH Act) as part of the American Recovery and Reinvestment Act (ARRA), adoption and use of electronic health records in the United States has dramatically increased.  Adoption of EHRs that met the criteria for a basic EHR system by office-based physicians grew by over 80% between 2009 and 2012, from 22% in 2009 to 40% in 2012.  Among nonfederal acute care hospitals, adoption of at least a basic EHR system has increased by over 260% since 2009, from 12% to 44%, according to a recent notice in the Federal Register.

Adoption of many of the computerized functionalities associated with Meaningful Use has substantially increased among both office-based physicians as well as hospitals.  For example, physician adoption of five core Meaningful Use functionalities---ranging from e-prescribing to clinical decision support--has grown by at least 66% since HITECH in 2009. 

While HHS has taken major steps to expand the functionality and utility of EHRs to providers and patients, the agency also seeks to engage other policy areas within HHS jurisdiction to promote routine sharing of information among health care providers across settings of care to support care coordination and delivery system reform.  The agency, however, recognized that economic and regulatory barriers may impair the development of a patient centered, information rich, high performance health care system where a persons’ health information follows them wherever they access health care services.

The Medicare and Medicaid Electronic Health Record (EHR) Incentive Programs and Office of the National Coordinator (ONC) for Health IT (HIT) Certification Program are increasing standards based health information exchange (HIE) across health care providers and settings of care to support greater coordination of health care services. 

However, this alone will not be enough to achieve the widespread interoperability and electronic exchange of information necessary for delivery reform where information will routinely follow the patient regardless of where they receive care.  With fee-for-service reimbursement and other business motivations often being the stronger influencer of provider behavior, both providers and their vendors do not yet have a business imperative to share person level health information across providers and settings of care.

For example, in 2011, 4 in 10 hospitals electronically sent laboratory and radiology data to providers outside their organization; however, only 1/4 of hospitals could exchange medication lists and clinical summaries with outside providers.  In addition in 2011, only 31 percent of physicians are exchanging clinical summaries with other providers.  Only 6 percent of long-term acute care hospitals, 4 percent of rehabilitation hospitals, and 2 percent of psychiatric hospitals have a basic electronic health record system.  Close to 1/3 of all Medicare beneficiaries discharged from acute care hospitals are discharged to post-acute care settings such as rehabilitation hospitals but there is little capacity in the system today to support HIE across these setting.

As a result, the Centers for Medicare & Medicaid Services (CMS) and the Office of the National Coordinator for Health Information Technology (ONC) released a Request for Information (RFI) on HIE, outlining several potential new policies using existing authorities and programs – such as requiring or encouraging Medicare Accountable Care Organizations (ACOs) to exchange health information as a part of coordination of care across aligned providers or patient engagement strategies – to accelerate interoperability and exchange of patient health information across care settings.  The RFI also sought public input about policies that will “strengthen the business case” for electronic exchange across providers.  Comments were due on April 21, 2013.

As part of its 2013 plan to foster HIE, the agencies also note that they intend to promote the Meaningful Use program and the federal Blue Button initiative – through which Medicare beneficiaries can access their online health information – and take steps to strengthen program integrity.  In announcing the RFI, HHS said it will:

Set aggressive goals for 2013: HHS is setting the goal of 50 percent of physician offices using electronic health records (EHR) and 80 percent of eligible hospitals receiving meaningful use incentive payments by the end of 2013. 

Increase the emphasis on interoperability: HHS will increase its emphasis on ensuring electronic exchange across providers.  It will start that effort by issuing today a request for information (RFI) seeking public input about a variety of policies that will strengthen the business case for electronic exchange across providers to ensure patients’ health information will follow them seamlessly and securely wherever they access care.

Enhance the effective use of electronic health records through initiatives like the Blue Button initiative:  Medicare beneficiaries can access their full Medicare records online today. HHS is working with the Veterans Administration and more than 450 different organizations to make health care information available to patients and health plan members.  HHS is also encouraging Medicare Advantage plans to expand the use of Blue Button to provide beneficiaries with one-click secure access to their health information.

Implement Meaningful Use Stage 2:  HHS is implementing rules that define what data must be able to be exchanged between Health IT systems, including how data will be structured and coded so that providers will have one uniform way to format and securely send data.     

Underscoring program integrity: HHS is taking new steps to ensure the integrity of the program is sound and technology is not being used to game the system.  For example, it is conducting extensive medical reviews and issuing Comparative Billing reports that identify providers.

The goals build on the significant progress HHS and its partners have already made on expanding health information technology use.  EHR adoption has tripled since 2010, increasing to 44 percent in 2012 and computerized physician order entry has more than doubled (increased 168 percent) since 2008.

“The 2014 standards for electronic health records create the technical capacity for providers to be able to share information with each and with the patient,” said Dr. Mostashari. “Through the RFI, we are interested in hearing about policies that could provide an even greater business case for such information sharing.”

In addition to seeking public input, the RFI also discusses several potential new policies and ideas to accelerate interoperability and exchange of a patient’s health information across care settings so that they can deliver better and more affordable care to their patients

May 29, 2013

Physician Payment Sunshine Act: WSJ-Kaiser Editorial Discounts Value of Companies and Doctors Working Together to Find Cures

The average life span of Americans increased from 69.7 years in 1960 to approximately 80 years in 2007. This accomplishment could not have existed without physician-industry collaboration. Yet for Robert Pearl, Executive Director and CEO of the Permanente Medical Group of Kaiser Permanente, "Medical Conflicts of Interest Are Dangerous" and "for some patients, what their doctors don't tell them could be hazardous to their health."

The opinion piece published in the Wall Street Journal was written in response to the finalized regulations implementing the Physician Payment Sunshine Act—Section 6002 of the Affordable Care Act (ACA)—which in general, requires pharmaceutical and medical-device companies to disclose payments they make to doctors, hospitals and other health-care providers. The Centers for Medicare & Medicaid Services (CMS) will then post such payments on a public, searchable database and website, known as OpenPayments.

In an attempt to suggest that Kaiser is above all other institutions, Pearl notes that Kaiser adopted a policy to expressly prohibit these relationships nearly a decade ago as a way to preserve the "sanctity of the physician-patient relationship, and the trust of our patients." Kaiser's conflict-of-interest policy prohibits physicians from accepting anything of value from a vendor, serving on speakers' bureaus, or being paid to "consult" with drug and device companies.

However, in response to Pearl's opinion piece, Frederick W. Lewis, M.D., wrote that "Not all conflicts of interest are as clear as the examples given" by Pearl. Lewis recognized that although Kaiser physicians may not accept payments from medical-device companies, this doesn't eliminate financial incentives for them. "For every dollar not spent by the Permanente Group on patient care, another dollar will be available to pay the physicians, creating an incentive to withhold care"; and most patients are "unaware whether a doctor they visit is incentivized to provide care or to withhold care." Where is the Sunshine then for Kaiser?

In addition, William M. Glazer, M.D., an academic psychiatrist for over 30 years, maintained that Pearl's "dismissal of value from industry-medical collaboration flies in the face of abundant economic and historical information. His vision for Kaiser is dingy and void of innovation. Physicians prevented from industry consulting must work dutifully in their cubicles seeing more patients, prescribing more generic products and thereby fattening Kaiser's bottom line."

Moreover, Glazer asserted that "Kaiser's business model, like Wal-Mart's or Targets, emphasizes volume and low-cost—meet the current medical standard and no more. Kaiser doesn't perform expensive transplants and many other costly operations that mean a lot to afflicted patients but don't fit the economic model."

Nevertheless, Pearl asserts that the intent of the Sunshine Act is to "help reduce potential conflicts of interest for physicians or teaching hospitals that may have financial relationships with" drug and device companies, and that the Act helps "shed light on the magnitude of the problem." Unfortunately, Pearl completely ignores the significant evidence and literature in existence, which shows that physician-industry relationships and collaboration have minimal if any harm to patients and do not create bias in various types of relationships (e.g., guidelines, continuing education (CE), and research).

In fact, even CMS acknowledged both in the proposed and final Sunshine rules that the agency has "no empirical basis for estimating the frequency of [conflicts of interest], the likelihood that transparent reporting will reduce them, or the likely resulting effects on reducing the costs of medical care." Moreover, Pearl ignores recent data, showing that State transparency or disclosure laws have no affect on the prescribing patterns of doctors. 

Further, we have written extensively about overwhelming evidence, which shows that commercial support of CME does not influence or create any bias in such educational programs. See Cleveland Clinic; Medscape, and UCSF, all showing there is little if any bias in commercially supported CME.

Moreover, patients are not even aware of these relationships—in fact a recent survey from none other than Kaiser, shows that "42 percent of the public does not know the Affordable Care Act is still law of the land and is being implemented." Thus, almost half of America does not even know the Sunshine Act exists, and it is highly unlikely that of the citizens who know the ACA is law, they even have a clue what the Sunshine Act is—particularly since most physicians don't even know about the Sunshine Act, so how could they even tell their patients?

Additionally, only about one in 10 Americans report getting information about the reform law from federal agencies, such as the U.S. Department of Health & Human Services, so how will anyone even know when these payments are published and how to use the site? There is a high likelihood, however, that the Obama Administration will use funds to educate consumers about the Sunshine Act through its OpenPayments website.

Nevertheless, Pearl maintains that despite the Sunshine Act, potential conflicts of interest "will continue—and patients will continue to be at risk for potential harm—until physicians themselves stop participating in these relationships." Under Pearl's belief, no physician should ever communicate or even associate with industry—both violation's of the U.S. Constitution's First Amendment freedom of speech and right to associate.

Then, Pearl goes into a tirade about how pharma and device companies have "engaged in marketing and promotion strategy" and developed "consultative" relationships to "promote their products to colleagues." He does not acknowledge any potential value in these relationships; Pearl just seeks to distort their view and paint only a negative picture. For example, Pearl does not acknowledge research, which has shown that practitioners who restrict access to sales reps are slower to adjust to negative news about a drug on the market.

Pearl also ignores the fact that without physician-industry collaboration or relationships, we would not have over 5,400 medicines in development globally, and more than 70% of therapies in the pipeline are potentially first-in-class and could offer patients new treatment options, and a notable number of potential therapies target diseases with limited treatment options such as ALS and rare diseases.

He also forgets to realize that because of physician-industry collaborations, the death rate from heart disease has dropped nearly 60% and deaths from stroke are down 70% since 1970. The death rate from cancer has dropped 16% since 1990 and the death rate from HIV/AIDS dropped more than 75% from its highest point in 1995. Instead, he suggests that such relationships with advance innovation "are really part of a thinly veiled promotional strategy designed to increase sales, particularly for expensive products with high profit margins."

Moreover, he uses outdated and old anecdotes and evidence in an attempt to find any credibility for his argument, maintaining that companies still invite doctors to "attend extravagant dinners and participate as "faculty" at conferences being held at resort destinations, with all expenses paid by the pharmaceutical or medical-device manufacturer." These practices have been outlawed, banned, prohibited and non-existent for over five years now, and significant enforcement actions and federal settlements have all but made such activities a distant memory—for all except Pearl and his fellow pharmascolds.

In addition, he cites to social science research (without providing citations), of which there was never a measure on patient harm or negative patient outcomes, to suggest that "medical literature is full of examples of the pernicious impact that gifts and financial arrangements have on treatment decisions." Yet, as noted above, even CMS does not know the extent potential conflicts have on health outcomes and no one has shown any evidence of negative impacts—rather, what we have seen is that more pharmascolds and conflict-mania has discouraged physicians from learning about new therapies and collaborating with industry to improve their knowledge and ultimately their patients' outcomes.

Response to Pearl

A number of individuals responded to Pearl's article, calling it "misleading [to] the general public" causing patients to think "that a physician who partakes in a medical-education event at which a modest meal is provided." In his letter, to the WSJ, David M. Short correctly maintained that "the best physicians seek out information from every available resource", including medical-device and pharmaceutical company representatives. They must take every aspect into account and determine the best treatment that has the best prognosis with the least adverse events."

Short asserted that "Medical innovation can only advance if physicians are willing to participate in its advancement. Unfortunately, their participation takes time, thus they should be fairly compensated for their expertise and consultation." As a patient, Short noted that he has "experienced a vast difference in medical knowledge between physicians who seek out information from every available resource versus those physicians who limit their continued medical education to medical journals they never read or who have had their ability to obtain knowledge stifled by their medical-group employer."

Accordingly, Short noted that once "the Physician Payment Sunshine Act's database is made public, I plan to use it to seek out the most up-to-date and open-minded physician."

David Shaywitz, writing in The Atlantic, also criticized Pearl's article, maintaining that Kaiser "has it backwards." He noted that drug companies "would like to develop important new medicines that improve health and save lives. That's what gets every industry researcher I know up in the morning, and what keeps them going through the many highs and lows that characterize the scientific process."

Shaywitz recognized that while much early-stage research may occur in academic labs, "moving from research publication to validated drug is long, difficult, expensive, and very tricky -- not least because many academic findings turn out not to be robust enough to support new drug development."

Consequently, "To advance even a solid idea requires, ideally, close communication between industry and outside experts:

  • university researchers, who often developed the science and understand it the best;
  • practicing clinicians, who can describe where the medical needs are the greatest, and what properties an ideal therapeutic would have; and
  • patients, of course, who understand better than anyone else what they need, and where existing approaches may fall short.

As he correctly maintains, "We should strive to cultivate, not demonize, these sorts of interactions." Instead, Pearl and other pharmascolds call on the public to distrust "the physicians and university researchers who consult the most with industry, yet it's often these experts who are the smartest scientists or the most experienced clinicians – that's why companies seek them out." Instead of viewing these relationships as conflicts, Shaywtiz maintains that innovation between industry and physicians represents "interdependence," and "drug development is far too important, and far too difficult, for anyone to do by themselves."

Shaywitz recognized that Pearl and others are "stigmatizing (and increasingly, seeking to exclude) experts who are arguably the most worthy of our admiration." While industry and some physicians have been bad actors, so has academia, and Shaywitz argues that people "should be careful about generalizing from sensationalized examples to condemn everyone who works in pharma -- or in universities, for that matter."

And while Pearl assigns guilt to pharma and device companies for making large profits, Shaywitz recognizes that making high profits "is the means to the end of fulfilling" a critical mission—" the pursuit of new medicines."

His article also recognizes how the importance of industry relationships and collaboration will actually grow in the future, despite repeated attempts to stigmatize these interactions because increasingly, physicians will be called upon to explain why certain therapies are necessary. Thus, physicians "will be highly motivated to think especially critically about their therapeutic choices, and are likely to discover many instances where a powerful new medicine turns out to provide the best, most economical option -- when total costs are considered."

On the same side of the coin, "Medical products companies will also be under tremendous pressure to deliver medicines capable of rigorously demonstrating value . To understand what would be worthy of use, drug companies will need to speak to clinicians; rather than stick their heads in the sand, Kaiser physicians should engage with medical product companies, participate in this dialog, and help increase the chances that they'll be able to prescribe better medicines to patients in the future. Participating experts also deserve to be compensated for their time, as Kaiser can both well appreciate and precisely calculate."

Shaywitz pointed out that "Emerging information technologies are likely to play increasingly important roles in both assessing and enhancing value . Not surprisingly, leading academic digital health initiatives -- including both the Center for Assessment Technology and Continuous Health (CATCH) at MGH and MIT, which I co-founded, and the recently announced Center for Digital Health Innovation (CDHI), at UCSF, both explicitly seek to cultivate partnerships with industry, in particular the tech powerhouses of Cambridge and Silicon Valley."

Thus, "to have even a fighting chance, stakeholders -- pharma companies, university researchers, clinicians, and patients -- need to work together, and collaborate as if our future health depends upon it. It probably does," he concludes.

Moreover, Dr. Glazer maintained that his "30-year experience as an academic psychiatrist collaborating with the pharmaceutical industry belies Dr. Pearl's insinuation that such activity constitutes "a thinly veiled" promotion to increase sales." He concluded by noting that "as a patient suffering from a malignant disease, I want whatever it takes to help me live longer. I want doctors who can provide me with extraordinary interventions that include experimental or proprietary therapy. Those doctors collaborate with industry."


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