Policy and Medicine

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.”

PLOS and Their Ludicrous Assault on Global Health Foundations Collaborations with Industry to Create Cures for Infectious Diseases

 
In America today, being healthy does not just depend on what kind of insurance you have, how much money you make, or what your genetics are.  Instead, the quality of health care Americans receive depends on the drugs, diagnostic tools, and medical devices available for treatment. 

However, the availability of such tools depends on investment from pharmaceutical and medical device companies in research and development and clinical trials.  In fact, because the government is largely uninvolved in the creation of new drugs, devices and treatments, and mainly only regulates these products, the main source for improving health care comes from private industry. 

Americans however, still face tremendous difficulties receiving the treatments and drugs necessary to ensure a happy and healthy life.  Some individuals do not have access to clinical trials because of geographic limitations.  Patients in rural areas or inner cities often are unable to find health care institutions to provide them with the diagnostic tools and innovative treatments needed to address their medical problems.   

Even more problematic is that individuals suffering from rare diseases (orphan) are frequently unable to get treatment because medicines are unavailable or stalled by regulatory tape.  Additionally, patients wait and suffer as the Food and Drug Administration (FDA) reviews applications for drugs to be used “off-label,” even though in some cases, off-label use of a drug is the standard of care.  The lack of certainty and predictability at the FDA in its medical device approval process, as well as the low number of drug approvals this past year, highlights the difficult challenges the healthcare industry faces in trying to improve the quality of care Americans receive. 

Consequently, a number of non-profit foundations, charities, and advocacy organizations were created to address these challenges by providing grants and endowments to support medical research and to make available health care services to those in need.  Additionally, many grants help provide unrestricted access to drugs, devices, and diagnostic tools relevant to specific health conditions, and help streamline and approve life saving medication for chronic and deadly diseases such as diabetes and AIDS. 

An example of one major philanthropic foundation is the Bill & Melinda Gates Foundation, which regularly gives donations and starts initiatives aimed at improving global health.  For example, in 2005, the Gates Foundation announced a $107.6 million grant to the PATH Malaria Vaccine Initiative (MVI) to extend a public-private partnership between MVI and GlaxoSmithKline Biologicals to develop the drugmaker’s malaria vaccine for children in Africa. 

Despite the clearly beneficial effects these foundations have on improving deadly and debilitating diseases such as polio and malaria, a recent study from PLoS Medicine noted that one aspect of these organizations may be overlooked.  The article raised concerns that philanthropic organizations can have links with pharmaceutical or medical device companies, which “could” constitute a conflict of interest. 

Essentially, the authors use a framing bias throughout the entire article by stereotyping all corporations as organizations that negatively hurt patients based on the behavior of tobacco companies and other industries who have tried to influence public health, such as food, mining, and alcohol.  Such an approach is problematic because the authors themselves recognize that, “corporations make products that can improve health (such as pharmaceuticals and vaccines) and relationships between public health institutions and for-profit corporations can be seen as positive opportunities for corporations to improve public health.” 

Background on Private Foundations 

In the U.S., private foundations must qualify for federal tax exemption. Unlike public charities, they usually do not provide services directly, but instead make grants to other entities to fulfill the foundation's mission.  The authors noted that private foundations must not operate in a manner that benefits private interests.  Private foundations may receive most of their funds from a parent for-profit corporation or wealthy individuals and families, sometimes in the form of investments (gifts of stock) and cash endowments. 

Private foundations manage their endowments and grantmaking decisions in a variety of ways.  Some foundations, like the Ford Foundation, have investment committees composed of members of the board of directors. Others may manage foundation investments externally or as a collaboration of professional investment teams with members of the board. In most cases, the board of directors is responsible for overseeing that funding decisions are made according to a set of foundation grant-making criteria.  Typically these criteria are set by the founders and/or executive committee members, donors, and overall boards of directors of the foundations. 

Study and Results 

The study examined the five largest U.S. private and/or family foundations that focus considerably on global health, which included the Gates Foundation; the Ford Foundation; W K Kellogg Foundation; the Rockefeller Foundation and the Robert Wood Johnson Foundation, which is a philanthropic outgrowth of a Johnson & Johnson founder. The authors analyzed publicly available endowment disclosures with the U.S. Internal Revenue Service and stock holdings from the U.S. Securities and Exchange Commission. They also examined potential conflicts of interest of individual foundation employees. 

The authors found that in some cases, board members of foundations also sat on corporation boards that my benefit from foundation grants. In addition, foundation grants were sometimes associated with companies that are represented on a foundation board and are among its investments and partnership.  For example, the study noted that members of the Gates Foundation currently or previously were members of the boards or executive branches of several major drugmakers, including Merck and Novartis. 

The study also found that the Gates Foundation had stock holdings in Berkshire Hathaway, which has significant ownership in GlaxoSmithKline, Sanofi-Aventis Johnson & Johnson. The authors also noted that the Gates Foundation held stock in Merck at a time when it developed partnerships with the African Comprehensive AIDS and Malaria Partnership and the Merck Company Foundation to test Merck products.  Endowment investments in pharmaceutical and food companies were similarly observed among the Ford, Rockefeller, W. K. Kellogg Foundation, and Robert Wood Johnson Foundations. 

Conflicts of Interest 

After discussing these findings, the authors set out to address the issue of potential conflicts of interest within these private foundations.  To do so, the authors adopted the World Health Organization (WHO) definition of “potential conflicts of interest.”  Specifically, WHO recognizes that, “conflict of interest can occur when a Partner's ability to exercise judgment in one role is impaired by his or her obligations in another role or by the existence of competing interests.”  Under this definition, WHO states that “such situations create a risk of a tendency towards bias in favor of one interest over another or that the individual would not fulfill his or her duties impartially and in the best interest.” Additionally, the definition states that, “a conflict of interest may exist even if no unethical or improper act results from it.” 

Discussion 

Consequently, the authors recognize that “a private foundation clearly has the legal right to spend money however it wishes within the limits of the law.”  However, the authors take issue with the fact that private foundations may “influence the future direction of what programs will be introduced into a foreign community.”  In other words, the authors believe that since private foundations are not democratically elected, their decisions will not be in the best interest of the public, and those groups affected by such decisions have no remedy.  As a result, they offer three recommendations. 

First, they suggest that private foundations divest.  Specifically, they recommend separation between investment management and the foundation's board. They also noted the idea of creating a “blind trust” so that the foundation leaders are not aware of their corporate investments and avoids the possibility that investment knowledge influences program decisions. 

Second, they recommend transparency.  In particular, that private foundations fully disclose actual or potential conflicts of interest, such as corporate affiliations (directorships, advisory panels, funding receipt) and personal investment holdings. The authors also asserted that when board members should recuse themselves from the discussion and decision when necessary and can resign from corporate boards and sell stock.  It was also recommended that independent audits be used to routinely monitor the scope and management of potential conflicts of interest within private foundations.

Finally, the authors recommend that private foundations align their aid with community needs, and that foundation investment and program portfolios should incorporate representation from the intended recipients of its support. 

Conclusion 

While this study may have shown that board members on the world’s largest private foundations have multiple interests, the authors failed to show any direct or negative harm such interests had on public health.  To the contrary, the authors acknowledged the exact opposite.  Specifically, the authors recognized that private foundations contribute billions of dollars each year to improving global health, and without such funding, the world would certainly be in a worse position than it is today. 

Accordingly, besides the clear framing bias, the assertions and conclusions from this article are problematic for one simple reason.  As the authors acknowledge, they were unable to assess whether associations among board members resulted in a particular decision taking place.  In other words, the authors could not assess or find any causal relationship between board members having multiple interest and their decisions to fund or give grants in public health. Given this tremendous weakness, many of the recommendations contained in their article should be considered skeptically.  It is unfortunate but PLOS medicine a “Online Journal” has become a propaganda arm for those who think nothing that industry does is worthwhile. 

At a time when costs of health care are spiraling, should we really be criticizing foundations for donating billions of dollars to help improve global health?  Such criticism seems misguided and extremist.  The money these foundations provide assist pharmaceutical development grants.  For example, because of the grants provided by the Gates Foundation companies, such as Merck and GlaxoSmithKline have established partnerships to test:

•  Pneumonia and rotavirus vaccines (such as the ROTATEQ partnership and the Merck Vaccines network partnership with the Global Alliance for Vaccines and Immunizations network)
• Experimental malaria vaccines (through Medicines for Malaria Venture, an NGO), cervical cancer vaccines (through PATH, an NGO, and Merck's vaccine Gardasil), and
• HIV interventions (through the Africa Comprehensive HIV/AIDS partnership).

Do any of these grants or endowments sound like potential conflicts of interest?  In addition, Johnson & Johnson has entered a clinical partnership to develop new HIV-prevention technology, noting, “the work between Johnson & Johnson and the Gates Foundation is a strong, strategic, comprehensive relationship.”

Ultimately, the world must recognize that the bulk of the Bill & Melinda Gates Foundation's financial transfers in global health have been to programs developing medical technologies, with more than 97% of its financial disbursements directed to infectious diseases.  While only 3% goes to chronic noncommunicable diseases, the Foundation has given $9 billion in financial transactions that went toward 1,094 global health programs between 1998 and 2007.  Of this total, 42% was spent on health care delivery or increasing access to drugs, vaccines, and medical commodities, while an additional one-third was allocated to technology development (mainly for vaccines and microbicides) or basic science research, and the majority of the Foundation's grants are directed to researchers in the U.S.

These investments are made with one goal in mind: improving global public health.  As Americans, we should be proud of the grants that these foundations are making to help the world and while transparency and mitigating potential conflicts are important, no evidence has suggested such actions are necessary.  Yet foundations already have in place numerous measures to ensure the highest level of integrity in their funding decisions.  As a result, we should be applauding the work of these foundations, particularly because of their emphasis in funding researchers in the U.S.  If America hopes to remain competitive in health and science, the money these foundations continue to provide to U.S. researchers and global health efforts will be crucial for attracting and keeping the best and brightest talent in the world.

 

University Medical Centers COI Policies and Innovation: Talk the Talk but Not Walk The Walk

 
A small, but vocal group of critics has attempted to dismantle and stigmatize physician-industry relationships for a number of years.  In fact, many of these individuals make their careers writing “scholarly” articles about the potential conflicts of interest (COI) in such relationships and professing themselves experts in this area of ethics in medicine. 

Despite critics belief that industry-physician collaboration may create bias, the “overwhelming evidence that relationships between universities, physicians and the medical products industry benefit patients explains the ubiquitous calls to encourage such relationships.”  Unfortunately however, “accumulating ‘conflict of interest’ regulations in academic health centers, government and industry have had the opposite effect,” scaring away such collaboration and in doing so, stifling innovation.

Consequently, as Lance K. Stell, PhD, professor of philosophy at Davidson College, and Thomas P. Stossel, professor of medicine at Harvard Medical School and director of translational medicine at Brigham and Women’s  Hospital, pointed out in a recent commentary in Nature Medicine, “justifications underlying the regulations lack quantitative rigor, and the rules they enforce impose costly bureaucratic requirements of dubious benefit.”  Moreover, evidence shows that these COI regulations “have diminished the collaborations deemed beneficial to health enhancement.”

As a result, Drs. Stell and Stossel noted that, “every policy governing the relationships between academic medical centers and the medical products industry ‘talks the talk’, forthrightly affirming that these relationships are essential for drug and device innovation.”  However, they recognize that, “product innovation is in serious trouble when the same academic institutions profess to defend industry-physician collaboration while apologetically genuflecting to a COI regulation movement, the effect of which has been to suppress such collaborations.”

History of COI Movement

What is problematic about the current physician-industry collaboration atmosphere we live in today, according to the authors, is that we ignored warnings from nearly twenty years ago about “a new McCarthyism” in relation to COI policy.  Yet, instead of listening to this warning from Kenneth Rothman and rising to fight it, “we invited onto our campuses moralizing avatars dedicated to purging them of corruption, the seeds of which were supposedly sown by industry’s insidious exploitation of the freedom of association and of speech.”

Accordingly, “their white-glove inspections found traces of conflict in doctor’s pockets, on their desks, in their sample cabinets, in their food, in the programs of their professional meetings—everywhere.”  And instead “of critically evaluating and rebutting their allegations, chagrined, doctors acquiesced to round after round of prophylactic COI regulations, each iteration more intrusive than the last, delineating what must not be said, what types of association must not occur and what hard-earned rewards for excellence cannot be accepted by researchers and educators in our most prestigious halls of medical learning.”

Even more troublesome is that doctors are “still apologizing for these relationships,” when “the vast majority of these relationships have been free of corruption and, more importantly, have produced value for patients.”  Drs. Stell and Stossel noted that without doctors working with industry to translate their ideas into useful products, today, Americans would not have a vaccine to prevent hepatitis B, a major cause of cancer worldwide, and percutaneous catheters, which enable physicians to gain access to diverse organs for diagnostic and therapeutic procedures with great speed and minimal morbidity.

Where is the Evidence?

Drs. Stell and Stossel assert that, “insinuations of corruption by those who call for increased oversight and regulation of the interaction between academia and industry require quantitative evidence—for a start, providing a denominator as well as a numerator.”

While many critics can easily compose the numerator by mentioning “the same cases alleging corruption due to industry influence, many laced with hindsight wisdom, dredged up repeatedly and assembled into a narrative framework,” a denominator is almost always missing.  In fact, “the storytelling suffers from serious ‘denominator neglect’—the non-nefarious, noncorrupt, beneficial collaborations, over decades that dwarf the comparatively few cases that populate the numerator.”

As the authors point out, “when attending to the numerator, the misconduct rate is negligible. The numerator of supposedly substantive adverse outcomes due to industry relationships (excluding relationship disclosure lapses discussed below) barely adds up to two digits. Surveys reporting that over 90% of physicians have some type of financial interaction with industry, with 18% of them engaged in consulting arrangements, indicate that the denominator is orders of magnitude greater.”

Moreover, Drs. Stell and Stossel assert that, “the laundry list of adverse consequences of commercial relationships consistently invoked by COI policy framers— degraded research, neglect of teaching commitments, excessive secrecy, loss of public trust—has not materialized.” In addition, they recognized that, “speculation that commercial support of education inflicts undue bias, leading some universities to reject such support, is belied by extensive surveys reporting little impression of such bias.”

Another problem with the COI movement is their “jaundiced eye on failures to disclose payments from industry.” Critics “put stock in the marketing of a need for greater transparency—‘sunshine is the best disinfectant’.  However, this seemingly plausible mission is not so straightforward; its outcome measures are not defined, nor is its price considered.”

This presents a problem for physician-industry collaboration because the ‘sunshine’ afforded to the COI movement—now federally mandated as part of the Patient Protection and Affordable Care Act—will have a substantial impact on innovation.  While this expensive effort is intended to help the public to make informed judgments about whether their healthcare providers have been compromised, are biased or likely to be disloyal, “the data cannot reliably support such inferences.”

The reality is this data will not show the public what innovation is.  It will not explain to Americans that, “innovation is not academic research” and that, “academic institutions, especially elite ones, are incompatible with the mass-production and quality-control requirements of product development.”  Nevertheless, what this data should show the public is that “academia and industry have much to offer one another—if given the chance.”

And what Americans must realize is that this chance for academia and industry to collaborate and innovate, “requires a lot of trial and error to accommodate the unpredictability of biology and adaptation to serendipity associated with innovation.”  As a result, “requiring minute oversight and contractual specification of every interaction and staples of COI regulations are inimical to such flexibility.”

Innovation

Outside of collaboration, Drs. Stell and Stossel also emphasized that clinicians can only help patients if they know about innovative products.  However, the COI movement derides “industry marketing as qualitatively different from and morally inferior to academic education, which stigmatizes “practically useful information (and academic health centers market their services aggressively with far less regulation than industry).” “Worse, banning such marketing from campuses drives a care-impairing wedge between producers of drugs and devices and prescribing physicians.”

“The COI movement insinuates that industry cares only about returns on investments and nothing about the appropriate use of their products, a charge not only disrespectful but wrong. The COI movement perpetuates the prejudice that the medical products and academic medical industries inhabit separate moral universes: the former unprincipled and greedy, the latter altruistic and dedicated solely to science and service. The evidence is to the contrary: research misconduct has been more common in academic settings where workers are subject to far less oversight than in the medical products industry.”

Accordingly, Drs. Stell and Stossel assert that, “demanding regulation of COI represents a pejorative, framing bias. No party to any relationship wears the same hat at the same time and in the same way; no relationship aligns hat-wearing incentives perfectly. Physicians wear many hats, and industry workers do, too. Myriad descriptions characterize the complex, nuanced relationships between academic physicians and workers in the medical products industry. To impress onto this complexity and, by fiat, the taint of ethical toxicity requires strong justification.”

However, the COI movement has no strong justification.  Instead, they stamp all physician-industry relationships with “arbitrary bias, insinuating that physicians’ relationships with industry need toxicity management—eliminate, reduce, minimize or disclose, rather than proliferate, increase and maximize.”  Drs. Stell and Stossel “challenge the linguistic legerdemain that substitutes ethically suspect for mutually beneficial.”

Discussion

The “poisonous language” from the COI movement “has promoted damaging policies in academic health centers in some states and in the federal government. The damage is not merely rhetorical. It has discouraged academic-industry collaboration because both parties fear media opprobrium. Worse, burdensome compliance requirements burn precious resources that would better go to collaboration, research and education.”  Additionally, industry itself is also facing barriers to collaboration “thanks to the exploitation of COI rhetoric by prosecutors in league with whistleblowers, maladaptive US Food and Drug Administration (FDA) law and draconian penalties (i.e. debarment).

Drs. Stell and Stossel note that, “patients desperate for new and better treatments should be appalled—we all should be appalled.” They noted that, “abandoning this desultory course requires that our academic leaders return to walking the walk.

Rather than shrinking before poorly justified, slogan-ridden allegations of critics, sensation-seeking media and demagogue politicians, they should subject them to the same rigorous analysis they demand from their scientific endeavors.” This analysis “will steer them to recommitting their institutions to collaboration and cooperation with their industry partners.”

Ultimately, such changes are necessary because Americans expect “excellence in research, education, and patient care,” and physicians “should pursue [these goals] with no apologies.”

NEJM: The Selling of Academic Detailing

 
Almost 50 years ago, U.S. Senator Estes Kefauver (D-TN) introduced legislation to regulate the drug industry because the Food and Drug Administration (FDA) still did not have legal authority to require pharmaceutical companies to demonstrate that their products actually worked.  Before this legislation, “what physicians knew about prescription drugs was shaped predominantly by the claims their manufacturers made about them, and the evidence base underlying such claims was often rudimentary, or worse.” 

At this time, there was also an issue of “how information about a drug’s benefits and risks should be evaluated and communicated to physicians — and by whom.”  Of course then, as now, pharmaceutical companies used marketing.  However “no mechanism existed for robust, arm’s-length governmental determination of a drug’s efficacy and for the dissemination of such data — a solution that many clinicians did not favor in any case.” 

This legislation also created a mechanism to allow the federal government to “provide a more even-handed, public source of drug education for physicians: a leaflet that would accompany every prescription medication describing “all the information about the activity, uses, and untoward effects of the drug”; a compendium of such information for all products “in convenient and readable form” to be distributed widely; and an annual listof medications with high potential for serious side effects.” 

Eventually, Senator Kefauver held a number of hearings, which resulted in a new law that gave the FDA the authority to require evidence of efficacy and safety before a drug could be marketed. 

Consequently, a recent article in the New England Journal of Medicine (NEJM), written by Jerry Avorn, MD, analyzed the developments in drug marketing and labeling that have occurred over the past 50 years.  He noted that, half a century later, the question, “Who shall educate the physician?,” is still hotly contested. Dr. Avorn pointed out that the “evidence base available to clinicians to guide their therapeutic choices is still heavily shaped by industry-sponsored studies that often compare new products with placebo, measure their worth in terms of surrogate markers such as laboratory test results, or both.” 

In addition, Dr. Avorn noted that, “the recent comparative effectiveness movement holds great promise for improving this evidence base.”  However, comparative effectiveness is an economic analysis at its core, rather than a scientific compendium of drug safety and efficacy profiles.  Comparative effectiveness, according to current, global definitions, seeks to establish health outcomes, at a known cost.  Indeed, cost is a central outcome.  How comparative effectiveness will improve patient outcomes or health remains uncertain in terms of quality of life and treatment. 

He also discussed “concerns” about “undue influence of drug companies” in a “manufacturer-dominated continuing medical education industry.”  What is problematic about this comment is that it misstates the current state of the CME industry.  Industry funding of CME has been significantly reduced over the past several years, and now makes up less than half of all CME funding. 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. 

Additionally, Dr. Avorn’s belief that industry funded CME is producing bias or conflicts is unfounded because he provides no evidence to show that industry involvement in education is causing harm to patients, or that industry's absence from education would not increase harm.  

Interestingly, Dr. Avorn suggests that one way to address the issue of getting drug information to doctors is through “academic detailing” — educational outreach programs in which independent researchers and clinicians systematically review data for a given therapeutic area and develop noncommercial, evidence-based recommendations about treatment choices.  What is concerning about this comment is that Dr. Avorn fails to disclose the fact that he has worked on academic detailing since the 1980s and he runs a company—RX Facts—which provides these services to states and health systems.   

Despite this clear conflict of interest, Dr. Avorn describes how academic detailing involves sending pharmacists, nurses, and physicians to visit practitioners in their offices to present drug findings, drawing on the successful marketing strategies of industry but without its sales-oriented spin.  And he notes how several states, insurers, and federal programs currently fund academic detailing programs based on content developed by nonprofit organizations free of industry ties—most of which are funded through his company! 

Discussion 

Dr. Avorn’s failure to disclose his full involvement with academic detailing within the article is troubling, as are some of the statements he makes.  While he asserts that issues of drug marketing and education “are even more relevant and pressing today,” the reality is, industry is now developing fewer drugs and FDA approving fewer drugs. So it's not clear why or how the issue is "more pressing."  Of course, it is probably more pressing for Dr. Avorn because he stands to make more money through his company, gain recognition, and receive more grants if there is a need for academic detailing.   

Ultimately, while the idea of academic detailing certainly has promise because it could save smaller companies a lot of money they spend on sales representatives, academic detailing tends to focus on drugs with lots of supportive studies and especially generics.  These do little to establish the value and appropriate utility of new drugs/devices, which are often understood best after a substantial accumulation of direct experience.  Empiricism plays an important role in shaping hypothesis-driven protocols.  Also, many people seem to want to saddle drug companies with the cost of academic detailing while stripping the manufacturer's of input.  That's generally a lousy way to spend money. 

In the end, companies provide truthful, evidence-based data and information to doctors.  While academic detailing may be able to provide similar services, at what cost will this come to patient safety and health?  How will this effect physician knowledge, competency, and training? 

According to one CME physican leader “Shame on the NEJM who should know better than to publish anything with clear commercial bias that lacks any real evidence in their peer reviewed evidence based journal! They have violated the public trust and let down their physician readership that depends on them for scientific accuracy and unbiased review of articles.”  

If doctors didn’t want to talk to sales representatives, they would say no, as many have.  However, they find value in the information representatives provide.  Moreover, this form of commercial speech is constitutionally protected under the First Amendment, and attempts to prohibit the dissemination of truthful information are frowned upon in America.  Accordingly, underscoring one process that has been in place for 50 years to self-promote another is counterproductive.  We should be working together to get as much information to doctors as possible so that they are able to make informed decisions with patients to produce the best possible outcomes. 

JAMA: The Inverse Logic of the Pharmaceutical Inverse Benefit “Law”

 
In today’s fast paced and rapidly changing medical environment, health care practitioners in every area—from primary care to psychiatry and anywhere from surgeons to nurses—depend on new clinical information and data to learn about breakthroughs in science and medical technology.  While some health care practitioners can learn about such breakthroughs from colleagues and others can read about them in journals, a large majority of practitioners simply do not have the time to pour over piles of journal articles and clinical studies to find the pertinent information to help them improve their skills and knowledge.

Continuing Medical Education (CME) is also another option for health care practitioners to learn about new information and updates to guidelines and best practices in specific clinical areas.

Some practitioners even chose purely commercial events, sponsored by a specific pharmaceutical or medical device company to learn about a new product, treatment, use, or indication. Other health care practitioners learn about new drugs and treatments by participating in research sponsored in part or entirely by the pharmaceutical industry.

Throughout all of these interactions, health care practitioners depend on a certain level of interaction with industry. This physician-industry relationship is essential for many reasons, and without which, many patients could potentially suffer.

Consequently, one of the types of physician-industry interactions that has been heavily criticized over the past several years is marketing. Many anti-industry critics believe that pharmaceutical and medical device companies use marketing techniques, representatives, and other mechanisms to influence the clinical decisions and prescribing behavior of health care practitioners.

While no one can dispute that in the past there were abuses by some drug representatives and companies in discussing the off-label use of products with physicians or the provision of free meals and inappropriate gifts, times have changed significantly since then, and such behaviors are almost entirely non-existent. Policies enacted by PhRMA and AdvaMed have placed strict bans on gift giving, and numerous regulations from FDA, HHS, DOJ and OIG have made the risk and penalty for any illegal behaviors severe. And the enforcement of such rules over the past several years has increased dramatically through efforts to root out fraud and abuse in government programs such as Medicare and Medicaid.

Despite the vast changes in the way companies use their marketing budgets and drug representatives, Howard Brody, MD, PhD, and Donald W. Light, PhD, recently wrote an article in the American Journal of Public Health, proposing a “pharmaceutical inverse benefit law.”

According to the authors, this “inverse benefit law” is a heuristic device to help physicians understand how pharmaceutical marketing affects their decision-making process when prescribing medications. A summary of the article, published in the Journal of the American Medical Association (JAMA) without any balance, noted that the “authors' proposed law came about following recent highly publicized withdrawals of certain drugs from the market due to safety concerns.”

The JAMA article explained that the “law was inspired by Hart's inverse care law, itself inspired by the inverse square law of physics. Consequently, “the law states that the benefit-to-harm ratio among patients taking new drugs tends to vary inversely with how extensively the drugs are marketed.” JAMA asserted that, “the inverse benefit law highlights the need for comparative effectiveness research and other reforms to improve evidence-based prescribing.”

Accordingly, Drs. Brody and Light’s article “suggest 6 marketing strategies that create an environment in which prescribing certain drugs could undermine, rather than promote, patient safety and public health.” The 6 marketing strategies are:

• Reducing thresholds for diagnosing disease. For example, type II diabetes guidelines have gradually reduced the blood glucose threshold at which diabetes should be diagnosed despite a lack of evidence that tight control improves major outcomes. While early detection may provide more opportunities for diet and exercise to treat diabetes, if physicians prescribe hypoglycemics based on these thresholds, many more patients would be treated.
• Relying on surrogate end points. When physicians accept surrogate end points rather than improved clinical outcomes as goals of therapy, fewer patients need to be treated to demonstrate an improved outcome, even though that outcome does not directly benefit the patient. Surrogate endpoints also make it easier for marketers to be more persuasive about the first strategy, reducing thresholds for diagnosing disease.
• Exaggerating safety claims. By overemphasizing the safety of a new drug that has been used in relatively few patients, marketers encourage physicians to prescribe the medication to an expanded population of patients with milder symptoms, thereby exposing larger numbers of individuals to the drug, and therefore to the potential for adverse events.
• Exaggerating efficacy claims. When an expensive new drug performs no better than established lower-cost therapies but may have an advantage for a small subset of a patient population, marketers emphasize the latter to imply that the new drug is better than an established therapy, with the goal of its widespread use beyond the patient subset.
• Creating new “diseases.” For example, the invention of the “disease” categories of “prehypertension” and “prediabetes” potentially expands the patient population to be treated. But this approach requires treating much larger numbers of persons to benefit a few, while exposing all of those treated to potential adverse events.
• Encouraging unapproved uses. Because promoting unapproved uses of a drug is illegal, some marketers have used tactics such as manipulating the content of continuing medical education programs, hiring leading physicians to give presentations recommending off-label use, and sponsoring ghostwritten articles on off-label indications.

 

Discussion

In making these 6 claims, Dr. Brody noted he created this concept “to help physicians understand the subtle manipulation that they may face and should reject.”

If the manipulation is so subtle, then how are Brody and Light able to understand and identify it? What specialized training or expertise do they have in noticing this “subtle manipulation? Or is it that Brody and Light are making a living selling books and writing articles claiming that such “subtle manipulation” even exists?

Nevertheless, Brody noted that the main focus of their proposed “law” is on physicians and how our willingness to allow research published and promulgated by drug companies can lead us into doing things that seem quite innocent but that may have dire consequences.”

But what exactly are these things that “can” lead doctors to do things that have dire consequences?

Dr. Brody suggests the 6 examples above as ways that doctors “may” or “might” be “subtly manipulated,” however, he provides no evidence of how often this occurs. More importantly, he only describes the “potential” harm that could occur to patients, but does not include any evidence or harm to patients from this “subtle manipulation.”

While there have certainly been abuses in the past, which correspond to some of the marketing principles Dr. Brody has listed above, these abuses are extremely rare and limited to a few cases that were handled and corrected through legal and regulatory actions.

Physicians and health care practitioners are aware of these “6 marketing strategies” because they are highly trained professionals and can interpret scientific data without being influenced. Companies are not in the business of reducing thresholds for diagnosing disease. They make drugs to treat certain diseases and it is up to the scientific organizations and health agencies to set guidelines for proper diagnosis.

Moreover, companies are not exaggerating safety and efficacy claims because the FDA through DDMAC must explicitly approve such claims. If a company or drug representative made such exaggerations, it would be illegal, and companies have no reason to exaggerate such claims when the product is already approved.

Additionally, companies are not creating new “diseases” by expanding the patient populations. The reality is, Americans are becoming unhealthier by eating more and exercising less. Cancer, heart disease, diabetes, asthma, and numerous other rare and serious diseases still take the lives of millions of Americans each day. If expanding a patient population to help diagnose, prevent, and treat patients is creating a new “disease,” then we should applaud those companies who are helping to create the tests and guidelines to identify and treat these people.

Conclusion

In the end, the proposed new “law” to make doctors aware of “subtle manipulation” from marketing does more harm than it does good. It creates more unnecessary confusion about the information physicians are receiving and could harm patients when physicians refuse to look at studies or research or collaborate with industry for fear of “subtle manipulation.” 

Today, Americans are not living longer because of a better diet and exercise (clearly, just look at the obesity population). Americans are not living longer because the world is getting warmer.

Today, Americans are the living longer because there are medications and devices that prevent and treat disease. It is time to let doctors have the independence they need to evaluate sources of information. Doctors have enough to worry about with following guidelines, evaluating patients, ordering tests, and running their practices. There is no need to add another thing to their checklist, especially when looking for “subtle manipulation” would be like looking for a needle in a haystack.