Policy and Medicine

NEJM Article: Massachusetts Payment to Physicians Sites Old Statistics to Support Anti Industry Bias

Over the last several years, we have covered the Massachusetts Pharmaceutical and Medical Device Manufacturer Code of Conduct (PCOC), enacted in 2009.  Subsequently, the Massachusetts legislature rolled back some of the reporting requirements last fall.  And we recently noted that Massachusetts saw a 3% drop in payments to physicians in 2011.  

Consequently, several researchers—led by Aaron S. Kesselheim, M.D., J.D., M.P.H.—recently published a viewpoints article in the New England Journal of Medicine (NEJM) analyzing the distribution of industry payments to Massachusetts physicians.  The authors maintain that “relationships between pharmaceutical manufacturers and health care professionals remain controversial.”  For example, “meals and continuing medical education (CME) programs have been criticized for being promotional and have been linked to non–evidence-based prescribing practices.” 

This assertion is clearly outdated, incorrect, and biased.  First, the Accreditation Council for Continuing Medical Education (ACCME) has strict Standards for Commercial Support (SCS) that prohibit any CME programs from being promotional in any way, and explicity prohibit the involvement of any commercial supporter at any point in a CME program.  Moreover, the ACCME conducts regular compliance audits of CME providers and CME programs to ensure compliance with such standards and physicians are able to submit complaints of any inappropriate promotion or potential violations.   

Furthermore, the ACCME has the highest level of standards for accreditation that strongly require and demand the use of evidence-based materials and scientific literature in creating and presenting an accredited CME program, independent from any commercial support.  Clearly the authors are not familiar with either standards. 

Moreover, the authors ignore significant and overwhelming literature which shows that commercial support of CME does not influence or create any bias in such educational programs.  See Cleveland Clinic; Medscape, and UCSF.  In fact, we have cited numerous surveys showing that physicians overwhelmingly value commercial support of CME.  For example, a recent survey showed that 98% of respondents said CME/CE activities provided them with information that has helped them improve patient care. In addition, almost 60% believe the information that they gathered from accredited CME has helped them reduce the cost of the care they provide.  

Another survey showed that 89% of physicians valued industry providing research grants to doctors, hospitals, and medical schools.  Of those responding to the survey, 76% of participants said they attended an industry sponsored education program and about 9 in 10 attendees say information provided at educational programs is up-to-date and timely, useful, and reliable.  More than half of attendees said they often gain knowledge or skills helpful in their practice. 

The author’s suggestion that CME is not evidence based is also problematic.  We have written numerous times that CME, including commercially supported programs, have improved patient outcomes in areas such as multiple sclerosis, hypertension, COPD, ICU patients, improved taking of family history by physician assistants, Sepsis, healthcare-associated infections, reduction in CT scans, and several other areas.   

To bolster the appearance of a “problem” with physician-industry relationships, the authors use evidence of relationships from 2004, almost a decade ago, to estimate that “83% of physicians received gifts from industry.”  Such data is not only 10 years old, but also predates the PhRMA and AdvaMed Codes, changes in the AMA’s ethical policies, rules and standards, and much of the federal guidance and regulations from FDA and HHS-OIG.   

They attempt to use newer data from 2009, which showed “71% of physicians received gifts” but it is unclear exactly how they could have received such “gifts” when federal law (anti-kickback statute), the AMA, and industry trade groups ban them.  Likely, the research did not capture detailed data such as meals, reprints etc., and instead classified all payments as “gifts.”  They also cite to “social science” research which suggests that “gifts” of any value may influence prescribing decisions, however, such research never used patient measure outcomes.  Moreover, no research to our knowledge has ever shown negative patient outcomes from doctors who collaborate with industry. 

To the contrary, research has shown that practitioners who restrict access to sales reps are slower to adjust to negative news about a drug on the market.   

Methods 

Nevertheless, the authors used data from the Massachusetts database to calculate industry payments to physicians, make comparisons, and evaluate trends from July 2009 through December 2011 (the most current data available).  The Massachusetts database lists the name, address, and professional license number of each physician, the manufacturer, and the amount and purpose of the payment.  The purpose is categorized by the reporting company as one of the following eight types, with names and descriptors set by the state:  

1. compensation for bona fide services (including consulting and participation in speaker’s bureaus);
2. food;
3. grants and educational gifts;
4. CME programs, third-party conferences, or meetings;
5. education and training;
6. marketing studies (payments in conjunction with research “other than genuine research”);
7. charitable donations (excluding free samples); or
8. “other.”  

The researchers recognized that the federal Sunshine Act has similar descriptors for the “nature of payment” category, but that the ones currently used in Massachusetts are of limited value, since the dominant category of “compensation for bona fide services” encompasses “legitimate scientific as well as more controversial marketing relationships.” 

The researchers also matched each physician to a medical specialty using a publicly available data set managed by the state medical licensing board from February 2013 (historical data were not available) and compared the distributions received by various specialties. 

Findings  

The 30 months’ worth of data included 32,227 reported payments to 11,734 Massachusetts physicians, for a total of $76.7 million.  Of those payments, $17.1 million occurred in the last 6 months of 2009, $30.3 million in 2010, and $29.3 million in 2011.  In 2010, a total of 6530 physicians appeared in the database, as compared with 5921 in 2011. The average total payment per physician over the course of a year increased slightly, from $4,637 in 2010 to $4,944 in 2011. 

The most common form of payment was food.  During the 30 months, there were 14,251 payments for a total of $2.4 million (median, $100; interquartile range [IQR], $69–$164).  The number of food payments shrank from 5253 in 2010 (for a total of $858,031) to 4131 in 2011 ($811,292).  

Compensation for bona fide services was the payment type with the highest value. The 8432 payments in this category accounted for $67.3 million, or 88% of total expenditures (median, $2,750; IQR, $1,000–$6,560).  Such payments were made 3072 times in 2010, and the number remained stable in 2011 (2990). 

According to physicians’ specialty distributions, the researchers found that 25% of currently licensed Massachusetts physicians (8439 of 33,446) received at least one payment between July 2009 and December 2011.   

• Primary care was among the specialties least likely to receive payments: non-specialist internists (19%),
• Pediatricians (12%), and family practitioners (21%)
• Urologists (61%),
• Gastroenterologists (57%),
• Rheumatologists (51%), and
• Cardiologists (46%)  

The highest average per-physician amounts paid over the full 30-month period were received by orthopedic surgeons ($18,446) and physicians in various specialties within internal medicine, including endocrinology ($17,407), infectious diseases ($15,922), and pulmonology ($13,027).  

The distribution of types of financial relationships also varied among specialties. For example, compensation for bona fide services accounted for more than 90% of the payments for orthopedic surgeons, psychiatrists, and most internal medicine specialists, whereas general internists received larger shares of their payments in the form of food (8%) and grants or educational gifts (5%), and obstetricians received 11% of their total amounts as education or training.   

The analysis revealed decreases in overall payments and numbers of physicians appearing in the database between 2010 and 2011, with a slight increase in the average payment amount — when fewer physicians received payments from drug and device companies, the remaining financial relationships became a bit more lucrative. 

One explanation may be that relatively high proportions of physicians in Massachusetts are affiliated with academic medical centers and health systems that now have policies preventing physicians from accepting certain types of gifts of any value; institutions that have taken such actions include: 

• Boston University School of Medicine–Boston Medical Center (2007),
• the University of Massachusetts (2008),
• Partners HealthCare (2009),
• Tufts University School of Medicine (2010), and
• Harvard Medical School (2010).  

While payments for meals decreased due to the original July 2009 law, the repeal in the fall of 2012 will likely cause an increase in such meals, although there is no explicit definition of what “modest” industry-sponsored “meals and refreshments” are. 

Ultimately, journal articles such as this are evidence of what the future holds once CMS begins to publish payments under the Sunshine Act.  Articles such as this emphasize the critical need for having a “healthy dialogue” about physician-industry relationships to ensure that patients and the public understand their importance. 

NEJM Study Shows Doctors Mistrust Industry Sponsored Studies: Is Anti Manufacture Rhetoric Creating Prejudice Against Clinical Science?

The medicines that we as Americans take every day to help our hearts, our muscles, and our bones, improve our health and lead to happier lives.  Similarly, the drugs and devices designed to manage diabetes, cancer, HIV and other chronic diseases, have enabled those with such diseases to have better chances fighting such ailments.   

Receiving the fruits of such medicines, however, is the result of years and years of clinical research and close to $1 billion.  For a drug to receive approval from the Food and Drug Administration (FDA), several phases of clinical trials, including two large Phase III trials must be conducted, at the expense of the pharmaceutical company seeking approval.  Consequently, a recent article published in the New England Journal of Medicine (NEJM) raised concern over how company support of such clinical trials “can affect the design” and “reporting of the results.”   

Study 

Because little is known about how information concerning study design interacts with information concerning funding sources to influence physicians' interpretation of research, the authors conducted a randomized study involving simulated research abstracts to assess the role that disclosure plays in physicians’ interpretation of the results of medical research.  They developed hypothetical scenarios in which three new drugs were being evaluated for the treatment of disorders commonly encountered in primary care: hyperlipidemia, diabetes, and angina.  

The authors then created abstracts describing trials of these drugs in which they varied the drug being tested, the trial’s methodologic rigor, and the funding source.  For each drug, one trial had a high level of rigor, one had a medium level of rigor, and one had a low level of rigor.  The authors then added a variable describing the trial’s funding status.  Each abstract included one of three variations: no funding source mentioned, funding by the National Institutes of Health (NIH), or funding by a pharmaceutical company, with financial involvement in that company on the part of the lead author.  A total of 27 different abstracts describing a hypothetical new-drug trial were created.  

This methodology is problematic in itself.  The authors’ own bias was to show that industry-sponsored trials should be discounted or questioned solely on their funding.  Accordingly, there is a high likelihood that the “abstracts” were drafted by the authors with cues that might have biased the outcome.   Moreover, is it even legitimate to differentiate the quality of a study based on its sponsorship, particularly given that the cases were made by the authors? 

The authors the randomly indentified 503 physicians who reported spending 40% or more of their time and 21 hours or more per month in activities related to patient care and spending 50% or less of their time in the intensive care unit, the emergency department, or the cardiac catheterization laboratory.  The survey was given to these physicians between July 2011 and October 2011.  Each participant was presented with three abstracts, each of which described a trial of a different hypothetical new drug.  The survey asked physicians about their likelihood of prescribing the new drug, the level of methodologic rigor of the trial, and their confidence in the study investigators’ conclusions.  

Participants were also asked if pharmaceutical company funding was likely to influence the outcome of scientific studies about the efficacy and safety of pharmaceuticals in favor of the drug in question, and if they had received any financial support from manufacturers in the previous year.  

Results

Most of the respondents (75.%) reported accepting at least one type of industry suppport.  Respondents generally agreed with the statement that industry funding could influence the outcome of clinical trails of pharmaceutical agents in favor of the drug question (mean score, 5.4 out of 7.0).

The authors “found clear associations between the funding disclosure variations and physicians’ perceptions of a trial’s rigor and results.”  Regardless of the actual study design, physicians were less likely to view a trial as having a high level of rigor if funding by a pharmaceutical company was disclosed than if no disclosure statement was included.  Similarly, in comparisons with trials for which no funding was listed and regardless of the study design, physicians were less likely to have confidence in the results of trials funded by industry and were less willing to prescribe drugs described in such trials.   

These effects were even greater when industry-funded trials were compared with trials described as having NIH support.  In comparisons with NIH-funded trials, respondents were also less likely to describe industry-funded trials as “important”, and were less likely to want to read the full article.  However, “investigators in NIH-sponsored studies also have substantial incentives, including academic promotion and recognition, to try to ensure that their studies change practice,” said Jeffrey M. Drazen, M.D., in an accompanying Editorial in NEJM.  

Irrespective of the disclosure and level of methodologic rigor, physicians who strongly agreed that funding by pharmaceutical companies can influence the results of a trial were less likely to prescribe the hypothetical drugs than were physicians with lower scores.  Physicians who were older than the median age of 48 years for the sample were more likely than the younger physicians to report that they would prescribe the simulated drugs.   

Discussion  

In this randomized study, the authors found that respondents downgraded the credibility of industry-funded trials, as compared with the same trials randomly characterized as having NIH funding or having no source of support listed.  Physicians' skepticism of industry-funded research affected their responses to high-rigor and low-rigor trials similarly.  The authors proposed that “well-publicized controversies related to industry-funded research may help explain these findings.”  

For example, they noted reports of trials that withheld critical data; trials that presented positive results while withholding negative results; and industry-financed articles that were ghostwritten or published primarily as instruments of marketing.   

The authors recommended that companies seeking to enhance the appropriate use of important new products or to expand the appropriate uses of existing products “must address the attitudes” revealed in the survey “so that the credibility of the results of industry-supported trials are more likely to be based on methodologic rigor than on funding sources.”  Of course, the authors provided no suggestions of how to do so, since that was “not the subject of this research.”   

It was noted that journal reviewers and editors, those who conduct systematic reviews, or even interested physicians can refer to the ClinicalTrials.gov database to see whether trial data as reported reflect the planned study design.  They suggested that such a “retrospective check could alleviate concerns about the possibility that trial outcomes were changed after the data were gathered and analyzed.”  But the website may be incomplete. 

The authors also suggested that because NIH-funded trials had the highest level of credibility, increased funding by NIH or the new Patient-Centered Outcomes Research Institute (PCORI) might reduce clinicians' skepticism and lead to more data-driven changes in practice.  Interestingly, the authors failed to unravel two important aspects of such funding.  First, the government has minimal to no funds available for any hard clinical research; most funding is for basic research that amounts to Phase I of clinical trials, and pre-clinical trial research.  Second, funding from PCORI has its own tremendous conflict and bias: trying to reduce the cost of healthcare, making no distinction between what is truly effective and really seeking only what is “cost-effective.” 

The recent partnerships between NIH and industry, such as the new National Center for Advancing Translational Sciences (NCATS) may be a reasonable middle ground.   

What is ironic about this article, is the authors’ failure to acknowledge that the reason physicians are discounting research because of financial support is because the editors of such journals have created their own problem.  It is precisely because journals are publishing articles that demonize industry, that we have results such as this.  As we noted back in May, nearly 90% of articles published in high-tier medical journals emphasize the down-side of the medical products industry – with precious little evidence, false evidence and almost no effort at balanced discussion.   

In addition, the suggestion that media attention has also raised concerns from physicians is misplaced.  The overwhelming majority of large settlements have involved off-label promotion, not clinical trials or fraud related to such trials.  Thus, this article is merely feeding into the perception that anything and everything physicians do with industry is evil.   

Specifically, the authors maintained that some practitioners “may be swayed by potential bias in industry-supported publications to use certain medications more widely than would be appropriate, whereas other practitioners may be skeptical about the validity of company-funded research.”  To address these concerns, medical journals that publish the results of clinical trials have increased their transparency by including disclosures of financial support and/or conflicts of interest.  

The authors, however, maintain that “some financial disclosure may not fully address the problem of potential bias in published research results.”  For example, they point to one study that showed that physicians ignored disclosure statements, whereas other studies have shown that disclosure of substantial conflicts of interest can lead clinicians to discount the reported results of a trial.  On the other hand, the authors also point to some studies, which show that disclosure can “enhance the trustworthiness of the discloser.”   

What this study really shows is that the critics of industry-physician collaboration and those leading the “conflict-of-interest” mania have caused physicians to discount valid, truthful and scientific research, based not on the quality of the design, but by its funding.  Such questioning threatens the very knowledge our physicians depend on to improve their practice and care, which may ultimately harm patients.   

This research is problematic because it ignores the fact that physicians could be discounting valid and truthful scientific research because of such disclosures, which in the end, will only hurt patients and slow implementation of new evidence-based medicine and treatment guidelines.  As the authors themselves recognize, “pharmaceutical industry has supported many major drug trials that have been of particular clinical importance.”   

Moreover, they recognized that “Excessive skepticism concerning trials supported by industry could hinder the appropriate translation of the results into practice.”  In fact, they pointed to results of a large, well-designed trial describing a new use for a widely prescribed class of drugs, in which readers believed that the results of the trial did not justify a change in clinical management, citing industry funding as a key reason for this conclusion.  Despite their recognition, the authors continued to feed fuel to the fire of this “excessive skepticism.”  

Conclusion 

What is disappointing about this research is its failure to clearly acknowledge the adverse consequences this study will have on researchers.  While admitting that skepticism of research can “reduce the credibility and acceptance of even high-quality research that is industry-supported,” the authors offer no further elaboration on how to prevent such events from taking place.  Instead of citing ways researchers can rely on research and disclosures to prevent this kind of credibility reduction for high-quality research, the authors self-servingly hold true to their own bias and reason for writing this article: trying to prove that anything involving industry is bad; guilt by association. 

Ultimately, we have now come into an era where the editors and critics who once called for transparency are getting a taste of their own medicine.  Doctors, who try to rely on research from clinical trials to treat their patients, are now questioning the very truthful, valid, and scientific research such editors are publishing.  Is transparency really helping us?

Journal of American College of Cardiology: CME Contributes to Reduction in CT Scans

by Thomas Sullivan, Editor

Implementing a collaborative quality initiative, including a continuing medical education (CME) program, can reduce inappropriate use of cardiac CT angiography (CCTA) by 60 percent, according to results of a recent study published online in the Journal of the American College of Cardiology.  All referring physician specialties lowered inappropriate use rates in the study. 

“The study suggests that voluntary, mutually established quality metrics reinforced by education and feedback can result in major changes in inappropriate use,” Chinnaiyan said in a release. “This collaborative approach involving physicians, hospitals and payers may be applied beyond CCTA to enhance value in other areas of medicine.”

Kavitha M. Chinnaiyan, MD, director of advanced cardiac imaging education at Beaumont Health System in Royal Oak, Mich., and colleagues designed the prospective, observational study to evaluate the effectiveness of a statewide continuous quality initiative called the Advanced Cardiovascular Imaging Consortium (ACIC), which is sponsored by Blue Cross/Blue Shield of Michigan and includes 47 centers that perform CCTA.

“CCTA is a useful tool for defining the presence and severity of luminal stenosis in patients with suspected coronary artery disease (CAD). CAD is the most common form of heart disease in the U.S., according to the Centers for Disease Control and Prevention (CDC), and the leading cause of morbidity.  As a consequence, physicians may turn to exams such as CCTA to ensure against misdiagnoses.”

The article noted, however, that “using imaging as a crux has led to overuse and higher healthcare costs.”  For instance, the average cost of a CCTA ranges between $500 and $1,500, according to Blue Cross/Blue Shield of Michigan.  Reducing inappropriate use of CCTA, therefore, “would improve care while lowering costs for payers and the healthcare system.”

Chinnaiyan and colleagues collected data on 25,387 patients enrolled at centers participating in the consortium between July 2007 and December 2010.  The study span covered pre-intervention, intervention and follow-up periods.  To determine appropriate use, they applied criteria from the 2006 multisocietal guidelines (J Am Coll Cardiol 2006;48:1475-1497).  After data collection they used to 2010 updated criteria.

The intervention included:  

• A site-specific intervention led by clinical champions;
• An educational plan that included conferences with CME credits;
• Site-specific activities such as grand rounds and letters about imaging overuse and the possibility of losing third-party payer coverage in the absence of change; and
• Data monitoring that provided feedback on appropriate use adherence and a comparison to consortium members as a whole. 

Patients in the follow-up study group had higher coronary risk factors compared with those in the pre-intervention group and a higher percentage of normal coronary arteries.

Researchers reported a 60.3 percent decrease in inappropriate use, from 14.6 percent in the pre-intervention group to 5.8 percent in the follow-up group.  The rate of inappropriate use of CCTA decreased among all referring provider specialties.  In cardiology, inappropriate use changed from 13 percent in the pre-intervention period to 5.2 percent.  The changes in internal medicine/family practice and emergency medicine were 20.2 percent to 12.5 percent and 9.1 percent to 0.6 percent, respectively.

The authors noted that CCTA’s high sensitivity and negative predictive value is a strength, particularly for ruling out CAD.  The slight increase in normal coronary arteries in the follow-up group proved indirect evidence of a corresponding increase in the appropriate selection of patients, they proposed.

The study lacked a control group, and factors beyond the consortium such as the recession or regulatory actions may have contributed to the trend to curb overuse of CCTA, the researchers wrote. They concluded that while building such a consortium is complex and requires resources, it has implications beyond CCTA.

“Although the ACIC is a complex undertaking requiring resource organization at every level of the process (referral, scheduling, point-of-care and follow-up), such collaborative partnerships between payers and physicians could result in similar successes on larger scales,” Chinnaiyan and colleagues concluded.

Study Finds High-Impact Medical Journals Guilty of Anti-Industry Bias

Over the past few years, this website has been dedicated to highlighting the importance of ethical, physician-industry relationships that advance science and medicine and improve patient care and clinical outcomes. 

Economists have concluded that extensive interaction between academic researchers and practicing physicians with industry has facilitated the development and dissemination of biomedical diagnostics, devices and therapies.  Despite the significant improvements in healthcare, such as increased lifespan, decreases in death rates for cancer and cardiovascular disease, and better management of diabetes and hypertension, critics persist.  

A small, but vocal group, has consistently attacked these relationships, expressing their concern for “bias” and potential “conflicts of interest;” calling for everything from a complete ban, to increased transparency, which has culminated with the passage of the Physician Payment Sunshine Act.  These self-professed “ethicists” and “conflict of interest specialists” have made a career out of attacking physician industry collaboration—including some individuals who previously worked for industry.  They have sold and written books, given speeches, and even dedicated blogs to attacking such relationships.  

This has led to academic health centers, states and the federal government to institute regulations designed to monitor, limit or eliminate such interactions based on concerns that such relationships may degrade the performance and reporting of biomedical research and also induce physicians to behave in a manner inconsistent with cost-effective or ethical patient care—which are loosely defined under the operational term ‘financial conflicts of interest’ (COIs). 

While we are strong supporters of increased transparency, we have consistently recognized that giving the public information about how much a company pays a physician and using payment categories (i.e. consulting, education) is insufficient and does not provide the context needed to understand the complex nature of physician-industry collaboration.  

A recently released study highlighted the tension regarding the proper role physician-industry relationships play in advancing science and medicine and improving patient outcomes.  The study presents compelling findings about the bias nature of high-tier medical journals concerning these relationships.  Specifically, the authors conclude that "Prestigious" medical journals overwhelmingly make claims that industry research and marketing are corrupt and therefore collaboration corrupts doctors.  The media reports these articles and arguably, this influences policy.  The paper documents this fact and shows that the claims in journals are not backed by evidence and that balanced interpretation is lacking. 

The study, written by Roman Lesko, Samuel Scott, and Thomas P Stossel, MD, was supported in part by grants from the Association of Clinical Research Organizations (ACRO), The Association of Clinical Researchers and Educators (ACRE) and from the Searle Freedom Trust.  Prior to this publication, four medical journals rejected the paper, either subjecting it to impassioned negative reviews or refusing to review it due to “lack of interest.”  Nature Biotechnology journal published it despite such reviews. 

Study 

The authors sought not only to analyze whether the positive and negative aspects of industry-academic relationships were equally represented in top-tier medical journals but also to assess the weight of evidence in the COI literature that patient outcomes or public attitudes are indeed negatively affected by corporate interactions with academics and physicians. 

They analyzed papers published in four journals selected on the basis of their high (>20) impact factors: The Journal of the American Medical Association (JAMA), The Lancet, Lancet Neurology and The New England Journal of Medicine (NEJM).  They identified articles by performing keyword searches on the websites of the selected journals and on PubMed.  The 108 articles selected for analysis encompassed reports of original research, reviews, editorials and other commentaries. 

Publications on this topic began to appear in the 1980s and peaked around 2000.  The selected articles were published from the early 1980s to 2008.  Earlier papers primarily concerned research relationships.  Later papers addressed diverse industry-related activities, such as company marketing to physicians, corporate subsidy of physician education and other activities, use of professional writers of industry-sponsored publications or paying physicians to provide advice to investors in medical technologies.

Three readers analyzed the articles by posing four questions: 

1. Does the article emphasize benefits or risks of relationships, or is it neutral?
2. Does the article provide evidence, and, if so, is the evidence quantitative, anecdotal or both?
3. Does the article specifically draw conclusions regarding patient care outcomes or public concerns about relationships, usually described as ‘public trust’?
4. Does the article recognize and, if so, address, points of view contradicting its conclusions? 

Examples of quantitative evidence in the relationship-to-industry papers included compilations of the prevalence of all types of physician-industry or academic-industry relationships, effects of industry marketing on physician prescribing behavior, the influence of industry relationships on voting patterns of US Food and Drug Administration (FDA) panelists and results of surveys of physicians, patients or officials of academic health centers concerning attitudes regarding physicianindustry relationships. If an article presented evidence by citation of another article to buttress its conclusions, the conclusion was considered evidence-based.   

The authors determined whether an article addressed ideas contrary to its conclusions, noting whether the article critically analyzed opposing opinions, simply mentioned but did not attempt to rebut a different viewpoint or did not recognize a view other than its own.  Citing a less extreme opinion but one still on the side of the argument advocated by the article did not qualify as addressing balance. 

The preponderance of articles (n = 96, or 89% of the sample) unambiguously emphasized their risks.  In many cases, the risk emphasis was obvious from the paper’s title (e.g., “Just how tainted has medicine become?” or “Impugning the integrity of medical science: the adverse effects of industry influence”). These articles either did not discuss or only briefly mentioned benefits of physician-industry or academic-industry relationships, and all of them recommended more stringent regulation of such relationships 

For example, one commentary published in Lancet asserted that there is “grave danger because of the nature of its dealings with the pharmaceutical industry, the medical profession is forfeiting public confidence.”  The author, however, knew of “no firm data from opinion polls that would allow [him] to substantiate his hypothesis.”  Instead, he was “sufficiently impressed by comments from … the public, politicians … and the media.”  

Another research article concluded that the “medical profession needs to develop a more effective policy on conflict of interest” after looking at cardiologists’ connections with industry.  The products of the companies with which the cardiologists consulted, however, bore no consistent relationship to the consultants’ opinions.  In addition, a widely cited commentary used to justify institutional conflict of interest policies makes a wide-ranging claim that the most challenging and extensive conflicts of interest “emanate from relationships between physicians and pharmaceutical companies.”  The paper, however, provides no evidence to support this statement, which makes severe quantitative assertions (e.g. “regularly”).  

Findings 

Of these articles, 17% contained original data and were classified as research papers or else as ‘special articles’ by the journals in which they were published.  The rest were editorials or commentaries.  These two types of articles were analyzed separately. 

Whereas, by definition, all the risk-emphasizing research articles contained evidence, fewer than half of the risk-emphasizing commentaries did.  Half of the risk-emphasizing research articles and over two-thirds of the non-research articles included a statement to the effect that relationships to industry negatively affected patient care outcomes or caused public distress.  Of the total set of risk-emphasizing articles, nearly two-thirds contained no mention of an opposing point of view and only 5% critically analyzed it. 

Twelve articles either emphasized benefits of physician-industry relationships (9) or presented a neutral, balanced assessment (3).  All of the benefit-emphasizing articles presented some form of evidence to support their arguments and discussed an opposing viewpoint in detail.  The differences between the risk-emphasizing commentary articles and the benefit-emphasizing or neutral articles were statistically significant on key measures assessed in this study, including presentation of evidence, assumptions concerning patient outcomes and addressing an alternative point of view. 

Taking the above results into consideration, it is clear that the preponderance of articles published in the four highest-impact medical journals that publish primary research focused on problems concerning COI relationships. 

These articles differed qualitatively from benefit-emphasizing academic-industry relationship papers.  Most risk-emphasizing articles presented no evidence and many of the ones that did present evidence extrapolated that it had a bearing on patient outcomes or public attitudes.  This finding was “intriguing” to the authors because they were “unaware that such an effect ha[d] been established.”  On the contrary, three risk-emphasizing papers that attempted to identify adverse outcomes of relationships found little evidence for such consequences. 

Most risk-emphasizing articles made no mention of dissent from their risk-emphasizing views or opportunity costs of industry relationship regulation. In contrast, all the publications emphasizing benefits of relationships also explored the case made for risks of relationships.  The authors noted that, “the dominance of risk-emphasizing papers and the low prevalence of opposing viewpoints in those papers have contributed to the evolution of policies concerning academia-industry relationships.” 

Conclusion 

In an ideal scenario, policymakers faced with incomplete information engage in vigorous debate to deliberate different viewpoints.  Undermining this ideal is a phenomenon defined by behavioral economists as a ‘conformity cascade’.  In a conformity cascade, policy emerges not from an objective weighing of alternatives but from social pressure to conform and from lack of dissent.  

When an issue arises abruptly as a perceived problem, as exemplified by the flood of COI publications in the 1980s, and policymakers do not deeply study it but rather imitate opinions of influential others, especially in the absence of opposing arguments, the tendency is for them to take ever more extreme positions.   

This analysis reveals that the discussion of academic-industry relationships in top-tier medical journals has been unbalanced.  The authors wondered whether this imbalance has in turn negatively influenced policymaking, resulting in more restrictive policies than the evidence supports, particularly in terms of how COIs relate to patient outcomes or public attitudes.  It also points to the need for editors of top-tier journals to be open to a broader and more inclusive diversity of voices when considering articles on academic-industry relationships. 

Association of Clinical Researchers and Educators Press Release

In Defense of Anti Depressants and All Other Seriously Researched Medical Products

 
Recently, a number of articles have suggested that antidepressants are no more effective than placebos. Just last month, in an essay in The New York Review of Books, Marcia Angell-Relman, former interim editor in chief of The New England Journal of Medicine, favorably entertained the premise that “psychoactive drugs are useless.”

Earlier, a USA Today piece about a study done by the psychologist Robert DeRubeis had the headline, “Antidepressant lift may be all in your head,” and shortly after, a Newsweek cover piece discussed research by the psychologist Irving Kirsch arguing that the drugs were no more effective than a placebo.

To address the controversy surrounding the effectiveness of antidepressants used in Americans, Peter D. Kramer, a clinical professor of psychiatry at Brown University, wrote an article in the New York Times, “defending antidepressants.”

In Defense of Antidepressants

Kramer starts out by asserting that, “antidepressants work — ordinarily well, on a par with other medications doctors prescribe.”  He noted that, “certain researchers who have questioned their efficacy in particular areas,” have done so “on the basis of shaky data.”

The problem with these researchers using shaky data is that the notion that antidepressants “aren’t effective in general is influencing treatment.”

Kramer first offers support that antidepressants work from a study in France of more than 100 people with a particular kind of stroke. Along with physiotherapy, half received Prozac, and half a placebo. Members of the Prozac group recovered more of their mobility. Antidepressants are good at treating post-stroke depression and good at preventing it. They also help protect memory. In stroke patients, antidepressants look like a tonic for brain health.

What was surprising to Kramer was that a friend of his, who suffered from a stroke, was not put on antidepressants until after Kramer himself emailed his friend’s doctor. And even then, he learned from his friend, Robert G. Robinson at the University of Iowa’s department of psychiatry, that neurologists say they “don’t use an antidepressant unless a patient is suffering very serious depression” because “they’re influenced by reports that say that’s all antidepressants are good for.”

Kramer asserts that, “the serious dispute about antidepressant efficacy has a limited focus. Do they work for the core symptoms (such as despair, low energy and feelings of worthlessness) of isolated episodes of mild or moderate depression? The claim that antidepressants do nothing for this common condition — that they are merely placebos with side effects — is based on studies that have probably received more ink than they deserve.”

Evidence?

Kramer points out that the most widely publicized debunking research — the basis for the Newsweek and New York Review pieces — is drawn from data submitted to the Food and Drug Administration (FDA) in the late 1980s and the 1990s by companies seeking approval for new drugs. This research led to its share of scandal when a study in The New England Journal of Medicine found that the trials had been published selectively. Papers showing that antidepressants work had found their way into print; unfavorable findings had not.

In his book “The Emperor’s New Drugs: Exploding the Antidepressant Myth,” Dr. Kirsch, a psychologist at the University of Hull in England, analyzed all the data. He found that while the drugs outperformed the placebos for mild and moderate depression, the benefits were small. The problem with the Kirsch analysis — and none of the major press reports considered this shortcoming — is that the FDA material is ill suited to answer questions about mild depression.

Kramer explained that as a condition for drug approval, the FDA requires drug companies to demonstrate a medicine’s efficacy in at least two trials. Trials in which neither the new drug nor an older, established drug is distinguishable from a placebo are deemed “failed” and are disregarded or weighed lightly in the evaluation. Consequently, companies rushing to get medications to market have had an incentive to run quick, sloppy trials.

Often subjects who don’t really have depression are included — and (no surprise) weeks down the road they are not depressed. People may exaggerate their symptoms to get free care or incentive payments offered in trials. Other, perfectly honest subjects participate when they are at their worst and then spontaneously return to their usual, lower, level of depression.  Kramer explained that these problems are an “artifact of the recruitment process.” As a result, he noted that if many subjects labeled mildly depressed in the FDA data don’t have depression, this would explain why they might respond to placebos as readily as to antidepressants.

Research

Kramer explained how there are two sorts of studies that are done on drugs: broad trials and narrow trials. Broad trials, like those done to evaluate new drugs, can be difficult these days, because many antidepressants are available as generics.

Narrow studies, done on those with specific disorders, tend to be more reliable. Recruitment of subjects is straightforward; no one’s walking off the street to enter a trial for stroke patients. Narrow studies have identified many specific indications for antidepressants, such as depression in neurological disorders, including multiple sclerosis and epilepsy; depression caused by interferon, a medication used to treat hepatitis and melanoma; and anxiety disorders in children.

New ones regularly emerge. The June issue of Surgery Today features a study in which elderly female cardiac patients who had had emergency operations and were given antidepressants experienced less depression, shorter hospital stays and fewer deaths in the hospital.

Broad studies tend to be most trustworthy when they look at patients with sustained illness. A reliable finding is that antidepressants work for chronic and recurrent mild depression, the condition called dysthymia. More than half of patients on medicine get better, compared to less than a third taking a placebo. (This level of efficacy — far from ideal — is typical across a range of conditions in which antidepressants outperform placebos.) Similarly, even the analyses that doubt the usefulness of antidepressants find that they help with severe depression.

In fact, antidepressants appear to have effects across the depressive spectrum. Scattered studies suggest that antidepressants bolster confidence or diminish emotional vulnerability — for people with depression but also for healthy people. In the depressed, the decrease in what is called neuroticism seems to protect against further episodes. Because neuroticism is not a core symptom of depression, most outcome trials don’t measure this change, but we can see why patients and doctors might consider it beneficial.

Similarly, in rodent and primate trials, antidepressants have broad effects on both healthy animals and animals with conditions that resemble mood disruptions in humans.

One reason the FDA manages to identify useful medicines is that it looks at a range of evidence. It encourages companies to submit “maintenance studies.” In these trials, researchers take patients who are doing well on medication and switch some to dummy pills. If the drugs are acting as placebos, switching should do nothing. In an analysis that looked at maintenance studies for 4,410 patients with a range of severity levels, antidepressants cut the odds of relapse by 70 percent. These results, rarely referenced in the antidepressant-as-placebo literature, hardly suggest that the usefulness of the drugs is all in patients’ heads.

The other round of media articles questioning antidepressants came in response to a seemingly minor study engineered to highlight placebo responses. One effort to mute the placebo effect in drug trials involves using a “washout period” during which all subjects get a dummy pill for up to two weeks. Those who report prompt relief are dropped; the study proceeds with those who remain symptomatic, with half getting the active medication. In light of subject recruitment problems, this approach has obvious appeal.

Consequently, Kramer explained how a study conducted by Dr. DeRubeis, an authority on cognitive behavioral psychotherapy, was problematic because it was built around his own research. Overall, the medications looked best for very severe depression and had only slight benefits for mild depression — but this study, looking at weak treatments and intentionally maximized placebo effects, could not quite meet the scientific standard for a firm conclusion. And yet, the publication of the no-washout paper produced a new round of news reports that antidepressants were placebos.

Conclusion

In the end, Kramer asserted that, “the much heralded overview analyses look to be editorials with numbers attached. The intent, presumably to right the balance between psychotherapy and medication in the treatment of mild depression, may be admirable, but the data bearing on the question is messy.”

As for the news media’s uncritical embrace of debunking studies, Kramer suggested that this trend is based on a number of forces, including, “misdeeds — from hiding study results to paying off doctors — that have made Big Pharma an inviting and, frankly, an appropriate target.

That said, the result that the debunking analyses propose remains implausible: antidepressants help in severe depression, depressive subtypes, chronic minor depression, social unease and a range of conditions modeled in mice and monkeys — but uniquely not in isolated episodes of mild depression in humans.

Accordingly, Kramer noted that better-designed research may tell us whether there is a point on the continuum of mood disorder where antidepressants cease to work. Nevertheless, he recognized that “it is dangerous for the press to hammer away at the theme that antidepressants are placebos” because they are not, and to give the impression that they are is to cause needless suffering.

As far as other products, the effort that goes into researching a prescription product or medical device is amazing.   Perhaps some of that effort should be considered when judging products.

PLOS: Majority of Medical Students Value Interaction with Industry

 
The relationship between health professionals and the pharmaceutical industry has become a source of controversy and a major topic of concern for health services researchers and policymakers, as well as in the lay media. Physicians’ attitudes towards industry can form early in their careers, but authors of a recent article published in PLoS noted that, “little is known about this key stage of development.” 

The authors noted that, “while opinions about such relationships vary, physicians have a high level of exposure to industry marketing in a variety of forms,” which they claim affects clinical decision-making. 

For example, the authors noted that, “industry involvement in medical education occurs on multiple levels, including one-on-one meetings between trainees and pharmaceutical sales representatives (PSRs) and sponsored publications and educational events (such as Continuing Medical Education (CME) courses).” 

The authors also noted that, “because pharmaceutical companies recognize the potential for education to be used as a marketing tool, there is concern that such exposure may communicate a biased message encouraging overuse of particular products.” 

Despite this claim, a 2003 NEJM study commissioned by the RAND Corporation found that four times more Americans do not get (enough of) the medicines they need than
those who get too much or the wrong medicine. Even if aggressive industry marketing practices are responsible for 100% of excessive drug use, the problem of insufficiency is four times as large.  In this case, the question of appropriate access to medically indicated medications based on evidence-based recommendations has been grossly perverted. 

In addition, the references the authors cite related to overdosing—one about irresponsible Neurotonin marketing practices and the other about inaccurate sales information from drug reps—do not support their claim of patient over-medication, only an alleged predisposition by sales people to vigorously market their products and often with minimal discussion about alternatives.  However, FDA strictly limits claims sales people can make about their products, including indications and contraindications. 

Nevertheless, the authors claimed that, “interactions with PSRs can increase prescriptions of the drug being promoted and shift prescribing in ways that may not be consistent with evidence-based guidelines.” This can have the effect of physicians using “expensive treatments without therapeutic advantage over less costly alternatives.” The authors also asserted that, “industry sponsored education may also influence physicians’ ability to weigh the risk-benefit profiles of new, heavily promoted drugs.” 

They pointed to the case of rofecoxib (Vioxx) as an example, where the pharmaceutical manufacturer–sponsored educational materials downplayed the drug’s cardiac risks (a nearly 2-fold increased risk of heart attack and stroke). 

The authors propose that one reason why pharmaceutical industry marketing has an effect on physicians is that their attitudes towards industry and their propensity to be influenced by its marketing form very early in their careers. They assert that, “the socialization effect of professional schooling is strong, and plays a lasting role in shaping students’ views and behaviors.” 

As a result, the authors note that, “encouraging more rational prescribing among practicing physicians may require a better understanding of how medical students interact with the pharmaceutical industry.” 

Consequently, medical schools have already instituted guidelines for speaking and consulting relationships and mandated faculty disclosure of potential conflicts of interest on a public website. Many have argued however, that these restrictions are detrimental to students’ education and the future of biomedical research. 

Study 

To address the “controversy over the pharmaceutical industry’s role in undergraduate medical training,” the authors systematically examined the peer-reviewed literature through May 2010 to collect empirical data quantifying medical students’ exposure to and perspectives on pharmaceutical marketing practices, including relationships with industry and their behaviors related to prescribing and attitudes about important drug policy topics. Studies were separated, where possible, into those that addressed preclinical versus clinical training, and were quality rated using a standard methodology. 

The authors used PRISMA guidelines to determine the frequency and nature of medical students’ exposure to the drug industry, as well as students’ attitudes concerning pharmaceutical policy issues. They searched MEDLINE, EMBASE, Web of Science, and ERIC, as well as bibliographies of selected studies. Specifically, the authors examined:

• The extent of pharmaceutical industry interactions with medical students,
• Whether such interactions influenced students’ views on related topics, and
• Whether any differences exist between students in their preclinical versus clinical years or in different learning environments in relation to these issues.

Findings 

Using thirty-two studies the authors found that 40%–100% of medical students reported interacting with the pharmaceutical industry.  In addition, they found that:

A substantial proportion of students (13%–69%) were reported as believing that gifts from industry influence prescribing.

• Students were more approving of gifts to physicians or medical students than to government officials
• Clinical students (53%–71%) were more likely than preclinical students (29%–62%) to report that promotional information helps educate about new drugs

 The study also found that common types of interactions involved: 

• Gifts
• Industry-sponsored educational sessions, and
• Direct communications with sales representatives 

The authors found that 89%–98% of students in the clinical years reported having accepted a lunch or snack provided by the pharmaceutical industry and many of these students approved of meals, small promotional items, and gifts with an educational purpose, but were less accepting of social events and travel. 

In addition, up to 90% of surveyed students in their clinical years had received educational materials such as textbooks or journal reprints from industry. Overall, the authors noted that contact with the pharmaceutical industry increased over the course of medical school. 

When asked about the appropriateness of accepting gifts from industry overall, the majority of students in their clinical training years found it ethically permissible for medical students to accept gifts from drug manufacturers, while a smaller percentage (28%–48%) of preclinical students reported such attitudes. This same trend was seen in student opinion regarding whether physicians should accept gifts. 

One of the most consistently held student attitudes was the belief that education from industry sources is biased, especially among clinical students (67%–92%). Despite this, students variably reported (22%–89%) that information obtained from industry sources was useful and a valuable part of their education, with clinical students more frequently endorsing the utility. 

In most studies, almost two-thirds of students reported that they were immune to bias induced by promotion, gifts, or interactions with sales representatives in general. This perception of immunity to bias was prevalent in both the preclinical and clinical years. It appeared that students were more likely to report that fellow medical students (38%–69%) or doctors (13%–71%) are influenced by such encounters than they were personally (24%–63%). 

Students who interacted with PSRs were more likely than those who did not meet with PSRs to report positive perceptions of industry marketing and were less likely to perceive this marketing as negative. 

The authors also noted that students generally did not support excluding sales representatives or industry presentations from the learning environment, and student opinions were split on whether physician–industry interactions should be regulated by medical schools or the government. 

86% of American medical students reported that during their residencies they would like to interact with PSRs and 69%–77% of students across all studies endorsed faculty disclosure of conflicts of interest before lecturing.  However, most medical students reported not feeling adequately educated on physician–industry interactions with 62%–86% requesting more instruction in this area 

While 39% of clinical students reported being adequately educated on the topic, only 11% of preclinical students reported that the amount of instruction they received was sufficient.  The pharmaceutical industry was identified as one source of information used by students to learn about therapeutics (16%– 49%). 

Discussion 

Based on these findings, the authors asserted that students “are frequently exposed to pharmaceutical marketing, even in the preclinical years when learning is mostly done in the classroom setting.” Additionally, they found that the extent of students’ contact “with industry is associated with positive attitudes about marketing and skepticism about any negative implications of these interactions.” 

Consequently, the authors also noted that students’ opinions about the pharmaceutical industry differed between the preclinical and clinical years and with the presence “of policies restricting drug industry interactions with.  For example, compared with preclinical students, those in their clinical years reported more educational value in industry-provided material and were more accepting of gifts from industry—both to themselves and to professional physicians. 

The authors suggested that, “long hours spent working and studying and increasing financial hardship may have contributed to these feelings of entitlement.” However, we did not find anywhere in the survey that students felt "entitled" to gifts, only that they felt accepting gifts, under the circumstances described, was acceptable. Both the authors and editor introduce the inflammatory word 'entitlement' egregiously. 

In addition, the authors noted that one possible explanation why student attitudes change over the course of medical education is that “industry representatives are effective in directly molding medical students’ attitudes about these issues.”  They also suggested that the “characteristics of medical students’ learning environments shape attitudes about the pharmaceutical industry.” 

It was also noted that, “shifts in attitude that occur during the course of training may be attributable to clinicians’ greater confidence in their ability to objectively evaluate scientific evidence and distinguish credible information from overstatements in marketing messages. 

Conclusion 

What is particularly problematic about this study, is that there does not appear to be any misconduct, or any harms caused by the students as a result of their interactions with sales reps.  As far as we learn from the survey, the interactions are benign or potentially beneficial and there's nothing to suggest from the surveys that the students are not already capable of properly evaluating medical evidence.   

Moreover, the study’s conclusion suggests that because students were not more critical of PSRs during the survey, they must become more “professional” through censorship policies by their “more knowing mentors.”  Such an idea is disturbing considering the survey shows no evidence that the students are disrespectful of scientific principles or possess unprofessional values. 

Given that most student (22%–89%) believed that information obtained from industry sources was useful and a valuable part of their education, the results from this study show that industry’s relationship with students in all stages of medical education is valuable.  Moreover, because students used industry as a source to learn about therapeutics, it seems clear that removing such interactions and relationships could have a detrimental affect on patients and medical training and education. 

Additionally, with 86% of American medical students reporting that during their residencies they would like to interact with PSRs, prohibiting such contact could create more problems for these future physicians when they face PSRs in their own practice.  Accordingly, future research on medical student interactions with industry, throughout various stages of medical education, should focus on the potential negative impact removing these relationships could have on patient care and physician training. 

We should be encouraging medical schools and students to gather as much information from as many sources as possible so that students can be trained to learn how to objectively evaluate and differentiate truthful information from marketing.  If we continue to limit medical education from students, our next generation of doctors will be ill equipped to treat patients and train future generations of physicians.

 

Nature Medicine: Encouraging New Models of Industry Physician Collaboration

 
A recent commentary from Nature Medicine explained how recent “concerns about conflicts of interest have driven a wedge between academia and the pharmaceutical and devices industries.” 

The article, written by three researchers from the University of California, San Francisco, noted that, “Although elevated concern for bias is justified, particularly when academics may affect drug sales, partnerships between industry and academia are essential to achieve the full promise of health improvement from the public investment in biomedical research.” 

Instead of creating further separation between academia and industry, the authors asserted that, “new models for such partnerships should be encouraged” and policies should be created to ensure that these relationships continue to develop. 

“Conflicts of Interest”

Over the past several years, a few rare cases of “conflicts of interest” have occurred involving undisclosed financial ties between faculty at academic medical centers and industry, some with multimillion-dollar payouts to prominent experts.  These cases “have led to pillorying of the academics and, by association, their home institutions, putting a chill on ties between academia and industry.”

The chill has come from strict policies and rules prohibiting physician-industry relationships.  The problem with such changes is that “not all such ties are nefarious, and much value may be lost if collaboration is discouraged.”

There is no doubt that conflicts of interest have important consequences, particularly when bias could affect the approval or use of therapeutics.  For example, when a “lecturer recommends a treatment from a manufacturer with which he or she has undisclosed ties, a breach of trust has occurred. Similarly, conflicts may subvert the objectivity of guideline development.  Accordingly, the authors noted “the need for greater transparency and control of potential conflicts.” 

While increasing transparency is certainly appropriate to ensure that academic-industry relationships are viewed favorably, academic institutions have responded to revelations of conflicts of interest by setting policies that are more explicit. These policies include requiring full public disclosure of all financial ties, limiting campus access of pharmaceutical company employees and setting strict limits on the types of ties and amounts of compensation. However, in the heat of apprehension and sometimes embarrassment, “such policies may have unintended negative consequences, driving a wedge between academia and industry.”

For example, the need to declare travel reimbursement as a conflict of interest for attendance at an industry-sponsored professional meeting (the current policy at our institution) “seems an excessive regulation that stigmatizes useful and mutually beneficial relationships.” However, there is no place for promotional junkets, gifts and expensive entertainment, and personal compensation should never be the primary motivation for academics to work with industry.

Alternatively, the authors noted that, “relationships with industry that are not financial in nature but valuable to the academic investigator’s career—for example, deals involving access to industry-owned technology, use of databases or leadership of clinical trials—may not require disclosures in the current academic environment but probably should, as these are potentially significant sources of bias.” 

Consequently, policies at academic medical centers have created an “atmosphere of inquisition that has forced distance, causing many faculty to avoid contacts with industry in fear of being called out as corrupt.” And the press has continued to fuel this concern by publishing sensationalist articles discussing many prominent experts “for reasons other than glorious discoveries.” 

Physician-Industry Relationships 

Critics of industry cannot deny the importance of academic-industry collaboration in improving health.  “Academic researchers judge their relationships with industry to be very meaningful, and nonfinancial relationships may be as important as financial ones.” 

Physician-industry relationships include many examples of discoveries made and patented by universities, now licensed by pharmaceutical and device companies, and. several of these are blockbuster drugs with major health benefits and financial returns to academia. The discovery and development of imatinib— a highly effective and widely used cancer drug—is a compelling example. 

A scientist from industry, Nicholas Lydon, partnered with an academic investigator, Brian Druker, to identify novel compounds to inhibit a tyrosine kinase inhibitor implicated in chronic myelogenous leukemia (CML). The identification and early clinical testing of imatinib was recognized by their selection, along with Charles Sawyers, as Lasker-DeBakey Clinical Medical Research Award recipients in 2009. Imatinib is now recommended as first-line therapy for many patients with CML and has been credited with substantial improvements in quality of life. 

Although “Academic medical centers are a natural engine for biomedical discovery … academics also tend to be inefficient and distractible, and may not be focused on a mission of improving health.” Moreover, “academia is not charged or organized to bring therapies to the public … and faculty members often lack the knowledge and interest to identify discoveries that could form the basis for new therapies and to shepherd an agent forward through development.”  In addition, access is limited to funding and infrastructure to support the practical steps of translation. 

The role that academia and industry have in improving health through biomedical sciences is critical, considering the rate of new drug approvals continues to decrease.  Even with a profound increase in the funding of medical research over the last 20 years, the rate of new drug approvals has not increased. “Given that translation is generally dependent on passing the baton to industry, discouraging free discourse between academia and industry is likely to result in an even slower rate of new drug discovery.”

While some have suggested eliminating intellectual property concerns from academic discoveries to improve translational research, the authors asserted two reasons why this notion is problematic. 

“First, given the low yield of candidate drugs in development, the inability to control intellectual property would become a major disincentive for companies to invest the money required to take a potential drug through clinical testing to market, recently estimated to average $171 million; when failures are considered, the cost of development is estimated at $1.2 billion for a drug that ultimately is approved by the US Food and Drug Administration.” 

“Second, without free transfer of knowledge, skill sets and reagents between academia and industry, the energy of activation to move some discoveries into further development may be too great.” 

Conclusion  

The biomedical industry and academic investigators share the same goal of improving health and patient outcomes. For example, preclinical research, early-phase clinical trials, and incentives to produce reliable evidence and report it accurately are important to both industry and academics. However, several incidents in the past have impaired public trust in academic medical centers, which is troublesome because trust is a chief predictor of successful university-industry partnerships. 

To restore the trust in academic-industry relationships and collaboration, academic medical centers have begun to fully disclose and carefully manage research collaborations. These relationships should be disclosed “not as scarlet letters but as medals of pride.” Those capitalizing most on academic-industry collaborations are more likely to improve public health through new discoveries, a major accomplishment and the truest measure of success. 

Consequently, “new partnerships will need to reduce barriers, improve trust, preserve scientific freedom and deliver adequate returns for both parties: a tall order that will require careful planning and management.” 

Ultimately, the public benefits of discoveries made in academia are realized only when they have been translated into use through industry. Unlike academia, “industry is designed to effectively and efficiently produce and distribute therapies. Thus, academia and industry each have an essential role in improving health through biomedical discoveries.” Accordingly, we should be searching for ways to promote strategic research interactions between academia and industry, not setting policies that prevent them.

Archives of Internal Medicine: Older Medications are Always Better and Other Wives Tales from Critics of Modern Medicine

 
A little over ten years ago, while on vacation, I brought my son to a walk in clinic for an earache.  The physician working that day was very old.  As I discussed my son’s symptoms, we were both confused when the physician pulled out a crumbled piece of paper with a list of ten drug names written on it.

Apparently this aging physician had limited himself to the prescribing the ten drugs he had written on this paper, regardless of the problem.   Well he wrote a prescription from the list for a rather strong generic antibiotic. We went home and I threw out the prescription.  My son’s health issues resolved and we went back to vacation.

The idea of using a short list of medications regardless of the problem is still alive. 

The Archives of Internal Medicine recently published a slightly revised version of an old Journal of the American Medical Association (JAMA) article, with the same lead author—Gordon  Schiff, a past president of Physicians for a National Health Program (PHNP)—and  same content, replete with PNHP press release.  Most would consider this publication fraud.  Apparently, it is business as usual for these authors.

The article asserts that physicians should use a limited number of generic drugs—a “short list”—and ignore any new innovation. Of course, the media picked up on this with an article in the Chicago Tribune titled “Hold those drugs, doctor” based on a journal article by single payer proponent. Specifically, the article offers six principles that urge clinicians to:

Physicians and Prescribing Medications

 

Physicians frequently turn to medications to relieve suffering and prolong life, with more than 60% of people younger than 65 years receiving a prescription drug each year. As the authors recognize, it is “unimaginable for most doctors not to turn to the most up-to-date drugs in trying to do the right thing for the patient.” 

Yet the authors take issue with physician’s ethical and rational desire to want to help patients, by asserting that their desire to help patients with the “latest and greatest” drugs “is congruent with the messages and interests of the pharmaceutical industry. The authors claim that “medications are commonly used inappropriately,

overused, and associated with significant harm—suggesting the need to more thoughtfully weigh claims for drugs, especially new drugs.” 

As a result, the authors note an “alternate paradigm that represents a radical shift in prescribing attitudes and behaviors,” known as conservative prescribing. They explain that, conservative prescribing embodies an important new construct—the precautionary principle—an ecologic paradigm that stresses forecaring, the practice of anticipating potential adverse effects, even when cause-effect relationships are not fully established scientifically.

This approach places the burden of proving safety on the proponents of introducing a new chemical into the human ecosystem and thus encourages exploring alternatives to new drugs.  However, Cass Sunstein devastates the precautionary principle in his book The Laws of Fear (2005). The authors omit it from their bibliography. They also ignore that newly marketed ideas may be more lethal than newly marketed drugs.

Nevertheless, the authors assert that “mastering conservative prescribing is especially important for young physicians and trainees, who lack historical knowledge of past drug harms and withdrawals from the market. Early in their careers, when prescribing habits are being formed, they may rarely have encountered patients with serious drug-related problems or rarely experienced the anguish of realizing that a drug they prescribed harmed or even killed a patient.” 

To counterbalance these prescribing pressures, which include often unrealistic patient expectations, practice time constraints, and paucity of data and practical guidance, the authors identified six principles for safer and more evidence-based prescribing.

 Think beyond drugs

The authors assert that physicians should consider nondrug therapy, treatable underlying causes, and prevention rather than mainly prescribing drugs.  They also assert that clinicians should broaden their repertoire to become more skilled and effective at counseling and prescribing exercise, physical therapy, diet changes, smoking cessation, orthotics, or surgery when appropriate. The authors claim that, “substantial literature supports initiating nonpharmacologic measures as initial or preferred therapy for a range of conditions commonly treated with drugs, such as hypertension, diabetes, insomnia, back pain, arthritis, and headache.” 

Practice more strategic prescribing 

The article recommends that physicians “use only a few drugs and learn to use them well.  Specifically, the article recommends that physicians: 

• Defer nonurgent drug treatment;
• Avoid unwarranted drug switching;
• Be circumspect about unproven drug uses; and
• Start treatment with only 1 new drug at a time

In addition, the authors noted that, by becoming familiar with a limited number of drugs, learning in depth how to use a more limited subset of indications and mastering dosing, adverse effects, and interactions, physicians knowledge and experience with those medications will increase dramatically and those physicians will be in a better position to prevent errors and anticipate problems.

This principle also tells physicians to “Be Skeptical About Individualizing Therapy,” even though the authors recognize this runs “counter to the patient-centered care physicians seek to practice.” In fact, the authors claim that “individualization is a mantra of the pharmaceutical industry when it wishes to dismiss disappointing trial results, arguing that they apply only to average patients and not necessarily to the individual patient.”

Maintain heightened vigilance regarding adverse effects

Under this principle, the authors note that physician should:

• Suspect drug reactions;
• Be aware of withdrawal syndromes; and
• Educate patients to anticipate reactions)

Approach New drugs and Indications cautiously and skeptically

 The authors recommend that physicians:

•  Seek out information from trustworthy, unbiased sources;
•  Wait to die until drugs have sufficient time on the market;  
•  Be skeptical about surrogate rather than true clinical outcomes;
•  Avoid stretching indications;
•  Avoid seduction by elegant molecular pharmacology; (not sure who is seduced) and
•  Beware of selective drug trial reporting

Specifically, the authors assert that physicians should “avoid education from pharmaceutical representatives or “experts” with conflicts of interest, and instead turn to independent drug bulletins or specialists with reputations for integrity and conservative approaches.” They also recommended that physicians “evaluate claims for new drugs skeptically, insisting on evidence that they are demonstrably better than existing (drug or nondrug) therapy.”

In addition, the authors also recommended that physicians not “rush to use newly market drugs,” and instead, suggested the use of generics or a 7-year rule (i.e. wait 7 years before using a new drug). However, if everyone followed that rule of thumb, no new medicine would last that long on the market. 

Work with patients for a shared agenda

 The authors recommend that physicians:

• Do not automatically accede to drug requests;
• Consider nonadherence before adding drugs to regimen;
• Avoid restarting previously unsuccessful drug treatment;
• Discontinue treatment with unneeded medications; and
• Respect patients’ reservations about drugs

 Consider long-term, broader impacts

 Finally, the authors assert that physicians should:

• Weigh long-term outcomes, and
• Recognize that improved systems may outweigh marginal benefits of new drugs

 Discussion

 The authors acknowledge that “none of these principles is particularly novel,” but rather, taken together, they represent a shift in “prescribing paradigm from “newer and more is better” to “fewer and more time tested is best. Consequently, based on several incidents involving drugs with adverse events, the authors urge clinicians to take a more cautious approach to prescribing and administering chemicals whose effects are imperfectly understood. 

The reasoning behind the authors assertions and principles however, is flawed.  Many professional organizations and medical societies recognize the importance of physicians using new medicines and treatments to advance patient care and improve patient outcomes.   

For example, the American Association of Clinical Endocrinologists (AACE) recognized that endocrinologists have a greater responsibility than ever to educate physician colleagues, allied health professionals, and patients on the most up-to-date treatments and guidelines in endocrinology.  This is in response to the worsening national epidemic of poorly controlled diabetes and metabolic diseases, the shortage of endocrinologists to treat these conditions, and the rapid expansion of therapeutic innovations that can improve patient outcomes.

 Moreover, the article is listed as a “Review Article,” suggesting that the authors conducted a broad and balanced survey of scientific literature. However, the authors merely published opinions, with a bibliography to keep up appearances.  Reviews should not promote a singular point of view, but provide readers with the full range of data and interpretations on a topic.  This article clearly does not meet these criteria.

Additionally, the article does more than simply promote “conservative prescribing,” it advocates for incompetent care.  For example, the authors suggest limiting the number of drugs physicians prescribe, not because more may be better for patients, but because it may be too hard for physicians to know how to prescribe a large number of medicines.  So rather than promoting improved education, they promote simply abandoning an arbitrary set of valuable medicines.

Conclusion 

Ultimately, the authors “conservative” rationale is extremely flawed, and patients and consumers alike should be extremely concerned with any suggestions to follow such ideas. 

Americans need to ask themselves whether they want to live with yesterday’s medicines and treatments, or today’s technological advances and medical breakthroughs. Case in point: suppose that physicians had been adherent to author’s advice, “Do Not Rush to Use Newly Marketed Drugs,” when Lilly began marketing insulin. How many people today would have died and suffered from diabetes?

The Unhealthy Separation of Marketing and Education Support from Research

 

It is often quoted by critics that  "if only industry funded research alone and stopped spending on marketing or supporting education that the world would be a better place".  Today, there is even a conference  promoted by alternative medicine advocates dedicated to those ideals.  The thought is without marketing we would have some sort of medical nirvana. 

Realty is starkly different. If there is no marketing or education, there would be no product research, and even if there was research, no one would know about it anyway.    

It is naive to think that physicians will receive all their knowledge from medical journals, and even childish to think that medical journals who derive a majority of their income from product advertising would stay in business without advertising support from the same marketing dollars that many prominent journal editors are calling to eliminate.

How does it benefit patients if their healthcare provider has a total lack of knowledge about new therapies, techniques and procedures?   If there were no marketing or education, the multiple billions of dollars spent on research would come to naught and patients would suffer.

A study published in the Archives of Internal Medicine attempted to investigate the “subtle” bias or “potential conflicts of interest” in the most recent American College of Cardiology (ACC) and American Heart Association (AHA) guidelines.

We previously recognized that this article was problematic because the authors admit that, “the actual degree to which any individual may be influenced by any specific type of conflict of interest (or even a specific dollar amount) is impossible to assess.” Additionally, the study is biased because although several controversial episodes involving COIs in guideline production have surfaced in recent years, these incidents are extremely rare. 

In addition to these problems, many physicians argue that “conflict of interest” is not an appropriate term to describe the relationships that physicians have with industry. This phrase has been rejected by the Association of Clinical Researchers and Educators (ACRE) because it introduces a framing bias that restricts further discussion about the working relationships physicians have with the industry.

As Henry R. Black, MD, clinical professor of medicine at New York University School of Medicine pointed out, using “conflict” implies that there is a problem or argument, and we don’t believe that these relationships are a conflict at all.” Dr. Black explained that, “if anything, it’s a confluence of interest or a synergy of interest because CME providers and faculty have the same interest at heart, and that is helping patients.”
 
James N. Kirkpatrick, MD, assistant professor of medicine at the University of Pennsylvania and a researcher of the 2011 study, noted that clinical guidelines must be something that people can trust because they may have a beneficial effect on patient care.  As a result, Dr. Kirkpatrick asserted that we have to be “more cognizant of conflicts of interest, mainly because of the perception they bring.”  To do so, Dr. Kirkpatrick recognized the need for a transparent, open process to minimize conflicts of interest in clinical guideline making.
 
Physician Industry Relationships

Industry critic Eric G. Campbell, PhD, associate professor of medicine at Harvard Medical School, asserted that, “relationships between doctors and companies are ubiquitous in every aspect of medical education, medical research and the practice of medicine.”  He claimed that, “conflicts of interest are not universally bad, but they’re not universally good” because they have the potential to affect scientific research and patient care.

However, Campbell’s reasoning for such claims is problematic (as usual).  He goes on to cite the misquoted Wazana study, which recommendations suggested that industry-physician relationships affect the prescribing and professional behavior of physicians though these recommendations were not supported by the data presented in the same article.

Specifically, Campbell argued that industry-physician relationships are detrimental to the American public and these programs are meant to serve as a marketing tool to sell drugs.  Additionally, he argued that such programs have the primary goal of maximizing revenue. However, Campbell’s assertions are misguided because the Wazana study used no patient outcome measures and did not show a single negative clinical outcome.

Contrary to Campbell’s arguments, physician relationships with the industry are beneficial in that they typically lead to innovation that leads to new drugs and devices used to enhance patient care. For example, according to Thomas P. Stossel, MD, the American Cancer Society Professor of Medicine at Harvard Medical School, there has been a 50% decrease in cardiovascular mortality since new drugs and devices were introduced to help patients with cardiovascular disease.

Dr. Stossel asserted in a recent article in HemOnc Today that, “this decline in cardiovascular mortality is 100% because of the tools we got from the industry, and these tools were the result of physicians collaborating with the industry.”  Further, he added that, “these relationships lead to improved drugs, devices and imaging modalities. No one can get up and say that these relationships haven’t been overwhelmingly beneficial.”
 
J. Michael Gonzalez-Campoy, MD, PhD, FACE, medical director and CEO of the Minnesota Center for Obesity, Metabolism and Endocrinology, echoed Dr. Stossel’s comments and recognized that, physicians who are at the cutting edge of science and who are involved in clinical research are the best suited to author clinical practice guidelines.
   
Additionally, Dr. Black noted that academic physicians should not be expected to do what they do without any compensation.  Moreover, Dr. Black recognized that the problem with current disclosures is that they can be misleading since they make no distinction between the types of money received, such as that for a research grant or for honorarium, or speaking at industry-sponsored CME.

For example, Dr. Black noted that if he gets “a large grant sponsored by a company or received money to give talks, these would not be distinguished from each other.”  As a result, Dr. Black asserted that the nature of these disclosed relationships need to be distinguished.
 
Research Funding

One problem with recent press regarding physician-industry relationships is their failure to recognize that not all relationships between physicians and drug companies are negative. Pharmaceutical companies often provide most of the funding for clinical trials that evaluate potential new treatments for patients, and this funding is usually not available elsewhere.

Even Campbell recognized that if academic institutions refused “research funding from drug companies, we would not be able to live up to the public expectation” that academic research will make health services better for the American people.  Campbell further asserted that, academia needs “to work with industry because we need to translate the results of our research into health care products and service” in order to cure diseases, end suffering and educate the next generation of researchers.

Some believe however, that although collaborations between industry and researchers can be useful, there should be a firewall between the researchers and industry. Despite this belief, Gonzalez-Campoy recognized that the collaboration between physicians and pharmaceutical and biotechnology companies is what has made American medicine great. “One could not exist without the other,” he said.

He added that, “trials are designed not for marketing, but to fulfill regulatory criteria that allow medications and technologies to achieve the permissions and indications needed to come to market and benefit patients. It stands to reason that the compounds and technologies that are safe and effective are the ones that deserve attention.”
 
Dr. Black said the basic science research and clinical trials needed to bring a new drug or device to the market requires the expertise of physicians and fosters the collaboration between them and the industry.  “We would be nowhere without the relationships with the industry,” Black said. “The investment that a company makes to take an idea to market is about $1.2 billion.”
 
Uniform standards
The article also discussed the idea of medical institutions and journals having policies regarding conflicts of interest. Joel Lexchin, MD, professor in the School of Health Policy & Management at York University in Toronto, noted how “each journal, hospital and medical school has different standards, some being stricter and some looser. As a result, Lexchin and colleagues proposed a standard form for investigators to disclose conflicts of interest in an article published in the open-access journal Open Medicine.

However, Lexchin argued that simply declaring conflicts of interest is not sufficient because “unless you are an expert in conflicts of interest, you cannot be sure of the accuracy of what these doctors are saying, as they might be biased by their relationships with the company.”  Such reasoning is extremely problematic.  The idea that only “experts” can detect bias is not supported by any evidence and contrary to the years of training physicians receives to understand research and results. 

This kind of reasoning has led to disclosure policies now becoming a type of “confession.”  Dr. Stossel recognized that physicians have no problem disclosing in principle, but in practice, media are using disclosures to embarrass people, instead of crediting them for funding the studies.  In fact, a recent surge of articles from “investigative journalists” such as ProPublica, have been using payment data from drug companies—published in anticipation of the Physician Payment Sunshine Act—to write sensationalist articles about physician-industry relationships.  None of these articles discusses the benefits or positive outcomes physician-industry relationships create.

Physician-Industry Relationships: Debate

Steven Reidbord, MD, a psychiatrist in private practice in San Francisco, and chairman of the CME committee at the California Pacific Medical Center, asserted that industry sponsorship of CME is problematic and should be ended because “it’s impossible for most audiences to evaluate on their own, individually, whether the material presented is biased or not” and “it’s too easy to insert subtle bias in favor of sponsored products.”  However, he cites no evidence to support this claim, and ignores three very large studies from last year which showed almost no perception of bias in commercially supported CME programs (Cleveland Clinic; Medscape, and UCSF).   

He also claims that, “physician speakers who declare themselves beyond financial influence, and who sincerely aim to be objective, may unconsciously include biased statements despite their best intentions.”  Yet, he acknowledges that the ACCME has numerous rules to prevent obvious commercial bias.

But Dr. Reidbord believes that “no such rules can fully prevent monied interests from spinning things their way” because “there is too much profit at stake, and too many subtle ways to promote products.” As a result he believes that paying out of pocket to assure unbiased CME is a bargain in the long run.  Interestingly however, he believes that research, including by industry-employed physicians, cannot be divorced from industry because “taxpayer-funded research is politically untenable for now.”  To believe that industry can work in research but not education is hypocritical and illogical, especially considering taxpayer-funded CME is also highly unlikely.

Conversely, Michael Weber, MD, professor of medicine at SUNY Downstate Medical Center College of Medicine in Brooklyn, N.Y., noted that, “relationships between academic physicians and industry are not only a good idea, but also in some ways mandatory.”

He recognized that more than 90% of all physician interactions with patients result in doctors writing a prescription or recommending treatment. Academic physicians have a compelling interest, an absolute obligation to identify unmet needs in medical care, to come up with ideas and recommendations for how those needs might be met and to collaborate with industry in addressing them.

Dr. Weber noted that doctors are the best at seeing what unmet needs exist; understanding the sort of drug or device that might be in the best interests of patients; and designing studies and to being involved in the analysis and interpretation of studies.  On the other hand, doctors are not good at the highly complex process of drug development.  

He recognized that there are 1,000 or more steps between a good idea for a new drug to the point where the new drug can benefit patients. Managing that complex system of research, which consists of myriad of steps, is something that pharmaceutical companies do best. So, it’s a natural partnership. There are things that physicians can do better, and there are things that a pharmaceutical company can do better — the key is that physicians and industry are both working together as a team to create better care for patients.

In addition, who better to educate doctors than academic physicians? Dr. Weber noted that physicians are the ones who understand the issues and understand why treatments are different from each other and why newer therapies may have advantages or why older drugs may actually be more advantageous than newer ones. Further, he added that physicians are the ones who understand the clinical issues related to disease, so they can educate most appropriately about drugs or devices or other new interventions that fit in.

Conclusion

Ultimately, receiving compensation from industry for consulting, teaching or research should raise no serious concerns for critics such as Campbell or Reidbord because all professionals are paid for their valuable services. Compensation, provided that it’s transparent, is not the issue because doctors are more than capable of forming their own judgments about whether the research or CME they use is biased or not.
 

In the end, “it does not matter if it is agovernment agency, academic medical center or a pharmaceutical company” compensating a physician. Excluding the most expert physicians in the field because of their working relationships stands to hurt medicine and patients and it is “naive to suggest that physicians should not have fiduciary relationships for the work they do.” As Dr. Gonzalez-Campoy explained, physicians are paid for their work by third parties and this is what advanced science. Moreover, CME providers and faculty who work with industry all have the same interest at heart, and that is helping patients.

Accordingly, continued usage of terms such as “conflict of interest” and the framing bias associated with such terms will only increase the potential of harming patients, stalling advances and progress in medicine and science, and leaving physicians without the up-to-date training and education necessary to address the rapidly evolving medical landscape of the 21^st century.

Medical nirvana is patients going home from the hospital healed and increased life expectancy anything short of that is dire straights.

USCF Study Shows 56% of Physicians Think Commercial Support of Continuing Medical Education is Essential

 

A recent article from the Archives of Internal of Medicine has caused a number of media sources to discuss commercial support of continuing medical education (CME). The article, written by academics from the University of California, San Francisco (UCSF), focused on the results of a survey of under 800 participants at a series of 5 live HIV CME activities.   The information held mixed results as some of the questions focused on the potential for bias in single supported CME activities up to 86% of all participants and the consensus was that commercial support of CME was essential 56% of physician participants. The survey included 55% physicians, the remaining participants included nurses, physician assistants, and PhD’s.  

It should also be noted that a similar study conducted by researchers from UCSF (including Michael Steinman author of the archives paper) and published last year, found that 97% of respondents stated that the activity they attended was free of commercial bias regardless of whether the activity received commercial support or not.

Background 

The authors perhaps overstated their position in the very first sentence with this statement “pharmaceutical and medical device industry funding supports up to 60% of CME costs nationwide.”  But the authors clearly know this data is from 2006, and does not reflect the significant reduction over the past several years in commercial support of CME.  Specifically, since 2007, commercial support has declined $355 million or 29.3%.  Moreover, the total percent of commercial support as part of the overall CME budget dropped from 47.5% (2007) to 39.0% in 2009. Fewer companies are funding CME programs as well. Thus, do the author’s clearly frame their article with bias using out of date data, which they intentionally chose to use to bolster their claims?

Consequently, the authors then go into a discussion about reports from the Josiah Macy Jr. Foundation and the Institute of Medicine (IOM), which have recommended that all commercial support of CME activities be eliminated within the next 5 years.  These reports recognized  “that such a system may involve higher costs for physicians and require cost-cutting steps by education providers.” As a result, the authors sought to determine whether participants at live CME activities understand some of the costs involved, whether they would be willing to pay higher registration fees or accept fewer amenities to avoid or decrease the need for commercial funding, and how that willingness relates to their perception of bias related to commercial support. 

Study 

The authors conducted surveys at a series of live 1-day CME courses delivered by the International AIDS Society–USA (IAS-USA) from January through June 2009. The IASUSA is a not-for-profit medical organization that delivers CME programs for human immunodeficiency virus (HIV) specialists.  The organization requires that commercially supported programs receive unrestricted educational grants from several companies with competing products in the field.   

One of the problems with this study is that the respondents to the survey are clearly not representative of physicians as a whole.  Specifically, these were respondents who deal with HIV/AIDS patients, a very niche practice.  These are not general practitioners who deal with a wide range of diseases, conditions, and treatments, and who rely on CME to stay up to date on a vast array of medical information and data. Moreover, we are not told how many of the 400 physicians are in private practice vs. those in training or in academic centers.  Knowing this is important because those in training and those in academic centers do not rely on CME for continuing education.

Such an unrepresentative sample makes the results from this study skeptical. Especially considering three other studies from last year used more significant samples sizes and a more representative sample of physicians.  All three studies found a lack of commercial bias in industry-sponsored CME (Cleveland Clinic; Medscape, and UCSF).   

The survey items targeted 4 main areas (1) beliefs about commercial funding and potential for bias (10 items); (2) willingness to offset the cost of commercial support (10 items); (3) knowledge about some of the costs associated with providing a CME course (9 items); and (4) demographic information, including years in practice and types of interaction with industry in the prior 3 years. The survey items targeting the beliefs about commercial support and potential bias in CME were rated on a 4-point scale (eg, “no potential for bias” to “large potential for bias”). 

Findings 

Respondents reported that the greater the percentage of commercial support for an event, the greater was their perception of potential bias. For example, only 7% of physicians thought there was substantial (moderate or large) potential bias in activities without commercial funding, whereas 46%, 80%, and 86% reported substantial potential bias when a single commercial supporter provided 20%, 60%, or 100% of the activity total costs, respectively. 

“Substantial potential bias.”  What does this even mean?  While the authors have not disclosed the exact questions they asked respondents, one can only imagine:  Is it possible that when a CME program is funded with commercial support, there is a potential for bias? Of course people would answer yes, ANYTHING is possible! 

Is there potential that a car driving today hits you? Yes.  Respondents saying there is a “substantial potential bias” equates to meaning, “bias is possible.”  There is always bias in everything, and thus measuring its potential is insignificant.  

Moreover, this study did not ask participants about whether a particular activity was biased.  Instead, they just asked whether there was a “potential” for bias in any commercially supported CME.  Hardly a scientific question or way to measure what, if any, bias there could be in a CME program.

Overwhelmingly, physicians exposed to commercially supported CME do not perceive bias, even though they may well acknowledge the abstract possibility of bias. They may even acknowledge the possibility that a presentation may be biased and that they might misperceive it. However, what the authors need, but don’t have, is evidence that physicians are poor detectors of bias AND that the investigators, by contrast, are excellent detectors of bias. Surveys and subjective opinions cannot give such evidence.

The authors also noted that 70% of physicians perceived substantial potential bias when 2 or more commercial supporters completely funded the activity, whereas 86% reported bias when a single commercial supporter did so.  In addition, 73% of physicians perceived moderate to large bias from faculty members on commercial speakers bureaus and from faculty receiving research support from industry 68% compared with faculty who receive no funding from pharmaceutical/medical device companies 5%. 

The authors also found that fewer than half of the physicians (42%) were willing to pay increased registration fees if it meant commercial support would be less or nonexistent. In addition, physicians said that in order to reduce the amount of money industry spends on CME:

• 56% supported posting course curriculum online instead of in print
• 50% supported moving educational events to "less desirable" venues
• 50% supported ditching free food and snacks

The least desirable strategies for decreasing costs were to provide fewer topics and speakers (11%) or to credit fewer CME hours (15%).  

Moreover, 56% of physicians agreed or strongly agreed that commercial support is essential for accredited CME and should not be eliminated, while only 17% favored eliminating such support.  With over a majority of physicians agreeing that commercial support is “essential” for accredited CME, the authors seem to ignore this result and focus mainly on the “potential for bias.”  Clearly, the authors had predetermined what they wanted to prove, and were only interested in why commercial support leads to potential bias, and not why 56% of physicians find value in commercially supported CME. 

Discussion 

While this unrepresentative, small sample of physicians attempts to show that participants perceive a “potential” for bias in commercially supported CME, the authors attempt to connect this to physicians unwillingness to offset costs by paying more for CME seems misplaced. 

The idea that physicians are unwilling to pay more for CME, and thus not reduce the “potential for bias,” is one way to state it.  A different way at looking at the data is that because 56% of physicians agree that commercial support of CME is “essential,” there is no need to pay more for CME because doctors find value in commercially supported CME. 

Moreover, as the authors recognize, there are several approaches that are currently used to minimize the presence of bias in CME activities. The Accreditation Council for Continuing Medical Education (ACCME) sets standards and guidelines for monitoring of commercial influence, including tracking of declared of conflict of interest as well as for resolution of that conflict.  In addition, tools have been developed to help CME providers anticipate bias in activities that are at greater risk of bias. 

Despite these strong safeguards, the authors again use ACCME data from 2006 to suggest that 60% (now 40%) of revenue for commercial support of CME raises concerns “whether it is possible to prevent substantial commercial influence with such a funding structure.”  With a 20% decrease in funding over the past 3 years, such questions and concerns can hardly remain, especially given the strict ACCME guidelines. 

What is also problematic about the author’s paper is they clearly admit that there “is little direct evidence about the degree to which commercial support of CME activities introduces bias.”  If there is little evidence, and since their study produces none, on what basis do they assert their claims that commercial support of CME introduces bias? None.  More importantly, they point to no evidence that commercially supported CME has ever harmed a patient.  

Instead, the authors cite to “indirect evidence” that commercial support of CME shapes “both topic selection and presentation of information favorable to a company’s products or unfavorable to their competitors’ products.”  Such indirect evidence seems misguided for a peer-reviewed article, and could hardly be called evidence-based.   

Consequently, the authors discuss ways to provide quality CME either with alternate funding or at reduced cost. Some have suggested reducing costs by holding meetings and events at less expensive facilities and locations, or reducing speaker honoraria.  However, as the authors note, “a rapid reduction or elimination of funding might be unacceptably disruptive, and some have postulated that such a change will result in the disappearance of live CME as we know it and the development of other forms of CME.” 

The authors also point to an IOM study that estimated that if commercial supported CME is eliminated, the cost for physicians would go from $1,400 to $3,500 annually.  However, we are not told how IOM came up with these numbers nor what factors they took into consideration. 

For example, eliminated commercial support will likely reduce the geographic options for many physicians, meaning physicians will have to travel farther, take more time off from their practice, spend/lose more money.  In addition, less commercial support may mean that doctors have less programs they want to attend that address the specific issues in their field or training.  And of course, it does not address the issue of less education and training, and the negative impact this could have on patients. 

Finally, a commentary to this article noted that while studies have shown that physicians “perceive little commercial bias in the material presented, this does not mean that commercial bias did not exist, just that the attendees did not perceive significant commercial bias.”  What does this mean?  These authors talk themselves into circles. 

Perceived bias that exists or does not exist, what kind of medical degree or training do you need to assess whether there is bias in medical education?  Do we not put our physicians through enough training and education or is this bias so subtle we need a microscope or PET scan to find it? 

Conclusion 

The problem with this study is that the researchers from UCSF put surveys into the hands of doctors who were not only unaware of the costs of putting together a CME program (and specific costs such as accreditation, compliance, oversight, logistics, etc.), but were unaware that the present accreditation system and the firewalls from FDA, ACCME, and HHS/OIG are more than adequate to protect from bias. 

While the commentary calls for “minimizing bias,” the study did not prove there was any bias in CME programs, only that some physicians thought there was a “potential for bias.”  In fact, this survey did not prove there was bias in any CME at all because it did not ask about a specific CME program or activity.  Therefore, the authors of a study that says that healthcare professionals are aware that there might be a “potential” for bias, that does not in any way demonstrate that there is in fact any bias, jump to the conclusion that “we need to explore alternative models for CME programs and funding sources.”

This is a little like saying, “There is the potential for airplanes to crash, therefore I should take another form of transportation the next time I need to get from New York to Los Angeles.”  All the authors did in this study was make inferences about “potential bias.”  Such inferences were not reasonable because they had no evidence and were based on pure conjecture and speculation.

The future of CME depends on collaboration and innovation with multiple stakeholders to implement many of the goals and initiatives contained within the Affordable Care Act (ACA).  At a time when we are experiencing shortages of primary care physicians and our health care system is bleeding money due to inefficiencies, we should be spending our resources on finding ways to produce high quality care at an affordable cost, and focusing on outcomes.  The growing epidemics of obesity and diabetes will continue to cost our country billions of dollars, and educating our physicians throughout their lifetime will be critical to improving these horrible diseases.

Working with industry to provide education and CME is valuable for a number of reasons, none of which these authors examined.  Had they asked these questions in the survey, they would have found out why 56% of physicians feel commercial support of CME is “essential.”