Policy and Medicine

Letters to the Editor: Conflict of Interest in Authorship, and Disclosure in Industry-Related Scientific Publications: The Tort Bar and Editorial Oversight of Medical Journals

 

Last year, Laurence J. Hirsch, a former spokesman for the pharmaceutical manufacturer  Merck, wrote an 11-page commentary titled Conflicts of Interest, Authorship, and Disclosures in Industry-Related Scientific Publications: The Tort Bar and Editorial Oversight of Medical Journals. The article, which looked at the relationship between medical journals and physicians who work on behalf of trial attorneys was published by the journal Mayo Clinic Proceedings, along with a correction and was also accompanied by a editorial by William L. Lanier, the publication's editor in chief.

In response to the commentary, Mayo Clinic Proceedings received a large number of letters to the editor and other communications in response to the commentary by Hirsch and the accompanying editorial by Lanier. Below is a summary of the comments the journal received .

 

Jeffrey R. Garber, MD, President of The American Association of Clinical Endocrinologists (AACE) acknowledged the various “interests” that physicians have and stated that “there is no inherent conflict of interest in the working relationship of physicians with industry and government. Rather, there is a commonality of interest that is healthy, desirable, and beneficial.”

 

Dr. Garber further emphasized that “monitoring and regulating physician interaction with industry is the key to ensuring integrity has yet to be supported by balanced scientific evidence.” As a result, he supported Hirsch’s “cogent argument that disclosure requirements for journal editors who are entrusted with accepting or rejecting manuscripts or who publish their own manuscripts should be as rigorously scrutinized as those being aggressively promoted for the medical community at large–perhaps no more, but certainly no less.”

 

Patricia K. Baskin, MS Executive Editor, Neurology, along with her colleagues, criticized Hirsch’s article for misrepresenting the “importance of the intellectual contribution of first drafts of manuscripts.” They make this claim based on the assumption that “a common industry practice is to use a professional writer to generate a first draft of a manuscript to facilitate the engagement of a “guest” academic author.” In fact, the editors of this journal felt that Hirsch’s essay showed a “desire to cover up the work of professional writers.”

 

In response to their criticism, Dr. Hirsch noted that there was no suggestion of cover up of authors but rather, that “others often do less and should simply be acknowledged, case-by-case.” As a result, he concurred that the contributorship model of attribution may be preferable to current approaches” but, “whether one approach is “better” than the other remains to be seen.”

 

One of the more powerful comments in support of Hirsch’s article came from numerous clinical researchers and educators dedicated to the treatment of multiple myeloma. These physicians wrote their response because they recognized that one important factor has been missing from the discussion about the increasing scrutiny and regulation of the relationship between clinical educators and investigators and industry and the continuing medical education (CME) providers:

 

“a concerted response from those who have worked with the pharmaceutical industry and providers of CME to present the opinion that these interactions are in fact of real value.”

 

These clinicians are also worried about the valuable relationship of industry and CME because “evolving institutional and national trends now in the public domain may seriously curtail the interactions between clinical educators and investigators, industry, and CME providers.” If such interactions are prohibited or hurt, they assert that it “will diminish clinical investigation and education alike, with a consequent negative effect on patient care.”

 

Even more detrimental to patient care, the group noted, is that “many institutions are considering the adoption of a “zero involvement” policy, which would substantially limit physician involvement in CME activities and new drug development.” They noted that “although some rare abuses have occurred and that the risks in this interaction are real,” the medical community should avoid “overzealous, ill-judged, and restrictive regulations that will curtail the current constructive interaction.”

 

Specifically, clinicians emphasized that such partnerships “resulted in unprecedented advances in myeloma, with a subsequent dramatic improvement in patient outcome, and to impede this progress in the treatment of multiple myeloma would be a disservice to their patients and their families.” The group then went on to assert that:

 

1.   Synergistic interactions between physicians and the pharmaceutical industry have contributed to the development of safe and effective therapeutics that have improved individual patient outcome and thus have contributed to the greater good of society.

 

2.   The overwhelming majority of interactions between academia and industry have been positive, productive, ethical, mutually respectful, and driven by the shared desire to bring better treatments to patients with multiple myeloma.

 

3.   Conflict of interest concerns in these relationships have been exaggerated and diminish the integrity of physicians and coworkers engaged in clinical research in the public eye.

 

4.   The evidence points to the overwhelmingly positive aspects of clinician-industry interaction and that a “confluence of mutual interest” exists.

 

5.   That industry-academia interactions, conducting shared research under commonly agreed upon guidelines characterized by full disclosure and clear transparency, are in the best interests of all, and in particular our patients.

 

6.    Enforced disengagement of such partnerships will help no one and hurt many.

 

7.   The support provided by industry for professional meetings and publications designated to promote and foster research as well as education is a major factor in contributing to the clinical development and subsequent deployment of effective therapies in a timely manner.

 

8.   The support provided by industry to commercial CME providers, with independent review of content for fairness and balance, has resulted in the development and implementation of a variety of educational events directed toward physicians, patients, and allied health care personnel, which has improved their understanding of the disease, the benefits and risks of different treatment strategies, and the existence of additional resources to help in patient care. Through these educational events, the quality of care delivered to patients with myeloma has improved. By accelerating deployment of new therapies, lives have been prolonged and toxicities of treatment decreased.

 

9.   We believe that this learning activity is of high value to the recipients of such education, especially to patients. As such, remuneration to experts of content and presentation for their time (often spent away from family) is reasonable, necessary, and professionally acceptable.

 

10.   Consulting and participation in advisory boards by highly informed specialists with first-hand experience of novel therapeutics, both clinically and  preclinically, are important activities of high value to industrial partners during the development of safe and effective new drugs. Optimal sharing of this knowledge occurs with investigators who care for patients and are engaged in clinical research, thus representing a bona fide exchange of information; remuneration for this work is reasonable, necessary, and professionally acceptable.

 

One commentator recommended that a 10-year moratorium should be used for any expert who would sit on FDA or related advisory committees and severing all financial ties at least 2 years before volunteering for these committees through 5 years after the guidelines have been implemented. In response, Dr. Hirsch noted that such an idea is “precisely the kind of damaging forced disengagements between industry and physicians, academia and medical associations that Fonseca et al warn against and which are not supported by analyses of several hundred Food and Drug Administration Drug Advisory Committee deliberations.”

 

Joseph S. Ross, MD, MHS, of Mount Sinai School of Medicine, and Harlan M. Krumholz, MD, SM, of Yale University School of Medicine, also commented on Hirsch’s article, and criticized him for misstating facts. Hirsch defended his assertion about Ross and Krumholz’s articles because “there was no mention of any of the authors being compensated, nor of appearing as expert witnesses in court, etc. The disclosure statements in the 2 other publications mentioned that the authors had been compensate.” Dr. Hirsch did note a correction to a statement about compensation.

 

A clinician who treats patients with AIDS commented that “had great opportunity for profit not motivated the owners of these companies, AIDS drugs may never have been developed.” He further emphasized that “had the owners of these companies not paid the researchers adequately, they may not have been able to retain and engage the type of people who have led to these wonderful breakthroughs and advances in drug developments.” Consequently, he referred to the present trend as an evolving “witch hunt against pharmaceutical companies.” He called for judging the work of physicians and researchers on the “basis of what they do and what they accomplish, not on the basis of who pays them or how they are paid; on the basis of its quality and honesty, not by who writes the paycheck of the investigators.”

 

Conclusion

 

In the end, Hirsch acknowledged that he had received dozens of e-mails from readers in the United States, United Kingdom, Europe, and Latin America after publication of his commentary and Dr Lanier’s editorial. He noted that, “with a single exception, roughly 90% were supportive.” As a result, he asserted the need to stop the indiscriminate use of the term “conflict of interest, and instead use the more neutral term “competing interests.” Dr. Lanier added that, the overwhelming majority of communications were supportive as well. In fact, he noted that many comments dealt with the fact that journals, editors, and policy makers were using a one sided idea dealing with the ills introduced by financial COI, instead of discussing the larger “risk-benefit equation as it relates to the discovery, invention, and introduction of drugs and medical devices.”

 

Such support reaffirms the notion that “within the proper boundaries of full disclosure and compensation at fair market value for the effort involved, these interactions should not be limited, but rather encouraged with appropriate guidance and within agreed upon guidelines.” Moreover, the relationships with industry and physicians should be strengthened to further improve outcomes for patients,” because hindering the progress of such collaboration will only be to the detriment of all, in particular patients.

 

It is also important to remember that “we should not simply assume that because someone is paid either more or less or by one person or another person, that the quality of his or her work or his or her integrity is either better or worse.”

 

With that in mind, we agree with Dr. Lanier that “the long-established, sustaining principles of scientific method, peer review, and medical publishing do not need to be abandoned or undergo major revision in the current era … because these traditional rules can be used appropriately for the advancement of knowledge and the benefit of society.” In fact, “collaborations with industry by experienced clinicians, educators, and researchers are indeed beneficial and advance the state of health care.”

 

Rather than “close the door to evidence, debate, and proper decorum,” by excluding the involvement of industry and “mocking the core of science,” the medical community and public must “appreciate the enormous amount of high-quality research funded by industry to develop drugs and demonstrate their value.”

Ghost Writing: Crisis or Fact of Life

This past week we have received several journal editorials around the “evils of ghost writing”. 

On the writers defense it does not take much intellectual work to make something framed and titled “ghost” sound sinister.  We all grew up with visions of Ghosts waking us up at night from our dreams only to run into or parent’s rooms screaming.  This was re-enforced by attending endless horror movies which in from 1960 - 1980’s were released at a pace of once a week.

In one recent article in the Mens Sana Monographs titled “Of Sophists and Spin-Doctors: Industry-Sponsored Ghostwriting and the Crisis of Academic Medicine,” makes the claim that “Ghostwriting for medical journals has become a major, but largely invisible, factor contributing to the problem of credibility in academic medicine.”

The author, Leemon McHenry, uses a one sided approach to only “explain the harm done to academic medicine and to patients,” instead of considering the benefits. Most likely, McHenry has chosen to criticize ghostwriting practices because he has been a research consultant to the law firm of Baum, Hedlund, Aristei & Goldman, Los Angeles, California, since 2003. The firm specializes in “Drug Product Injuries” and has a list on its website. The article reads more like a trial lawyer’s newsletter on how to prosecute companies who use ghostwriters.

McHenry also acknowledged funding support from the Prescription Project and the Pew Charitable Trusts.

Ghostwriting

His article starts off by asserting that “pharmaceutical companies commonly employ ghostwriters to write or draft manuscripts that subsequently appear in peer-reviewed medical journals under the name of one or more academic researchers.” He goes on to claim that such ghostwriters create articles that “obscure the contributions of industry,” which as a result, “undermines scientific integrity and jeopardizes public health.”

It remains hard to see how providing valuable input on research, development, and clinical data at various stages, to expedite the timely publication of data “jeopardizes public health.” We find giant leaps of logic common in these types of commentaries.

McHenry goes on to discuss how early in the process of drug development, a pharmaceutical company will develop a “publication strategy” to identify target journals and "key messages" tied to the promotion of the drug. Such a practice is no different than any other business venture: if no one is going to buy or use a product, then why make it? In fact, television shows for decades have been screened by audiences to determine whether people will watch. Yet no one complains about the violence, inappropriate behavior, or the constant branding of products seen on television.

The author claims that the publication strategy is a problem because “manuscripts are developed with a focus on marketing goals and with little or no consultation from the eventual authors.” McHenry goes on to claim that such manuscripts that appear in “medical journal articles, letters to the editor and abstracts for professional conferences are designed to give the sales force tools to drive prescriptions."

Such a claim however, forgets that these prescriptions are the very same medicine and treatments that have reduced the death rate of cancer for decades, helped millions with heart disease, and made HIV a livable condition. Perhaps it is easier for the author to talk about prescriptions, since the company that pays him, often sues the doctors and drug company’s who make the medicine being prescribed.

Further evidence of McHenry’s bias towards plaintiff’s attorneys is the fact that although he believes ghostwritten articles are objective, “they conceal pervasive conflicts of interest.” In contrast, numerous articles we have published discuss at lengths the practices of journals, academic medical centers, and drug companies who all have strict guidelines for transparency and disclosure.

The article tries to account for the prevalence of ghostwriting by associating it with “legislation which allows drug and medical device manufacturers to claim that their business practices are protected from revealing secrets to competitors.” While the "Trade Secrets Act" certainly helps protect companies who take significant risks and make tremendous investments, any secrets McHenry is talking about are no different from the information and data protected by a patent, trademark or copyright.  

Although the article goes on to claim that “financial relationships compromise the credibility of the medical literature,” evidence of such bias is problematic. While the disclosure of financial interests has had a few recent mix-ups, the use of ghostwriting to help develop content produced by pharmaceutical companies does not compromise the integrity of the data or research. Does a law clerk who helps write an opinion or a staffer who helps write a bill compromise the integrity of our democracy? All are working for the common goal of helping more people.

In the end, ghostwritten papers do not undermine the integrity of science or the trust placed on individual clinicians and researchers because these professionals are aware of the contributions and work they receive.

Since McHenry acknowledges that “it is less than clear how many journal editors are seriously concerned about the ghostwritten papers they publish,” his position should call for more discussion, instead of criticism.

New York Times: Follow The Science Not the Money

 

Although recent media and government attention to conflicts of interest have centered on the medical world of physicians and the drug industry, a new development regarding COIs has come to the attention of one New York Times reporter in an article titled Corporate Backing for Research?  Get Over It.

The story of conflict focuses on Nobel Laureates Al Gore and Dr. Rajendra K. Pachauri, who won the prize in 2007 on efforts “to protect the planet from the ravages of greedy fossil fuel industries.” Their work however, came under scrutiny “journalists started looking at the money going to companies and nonprofit groups associated with Mr. Gore, and Dr. Pauchauri, the chairman of the United Nations Intergovernmental Panel on Climate Change (IPCC).

Dr. Pauchauri is now contending with accusations of conflict of interest due to his initial warnings of a “very high” likelihood that global warming would cause the Himalayan glaciers to disappear by 2035. In response to such an idea, “the Indian government subsequently published a paper concluding there was no solid evidence of Himalayan glaciers shrinking because of global warming.”

Putting these findings aside, Dr. Pachauri dismissed such research as “voodoo science” beneath the I.P.C.C.’s standards. His dismissal however, was deeply flawed because it relied on a claim by Syed Hasnain, a glaciologist who now works in an Indian research group led by Dr. Pachauri. Essentially, “the I.P.C.C.’s projection was based not on the latest peer-reviewed evidence, but on speculative comments.”

Not only did Dr. Pachauri apologize for this mistake, he also had to acknowledge his “worldwide portfolio of business interests, which included relationships with carbon-trading companies and his research group, the Energy and Resources Institute.”

In his own defense, Dr. Pachauri responded that “he had not profited personally and that he had directed all revenues to his nonprofit institute.” Such an assertion highlighted the common and unfortunate reality of conflict-of-interest accusations that too often “follow the money” even though it leads to nothing but “cheap ad hominem attacks.” As we usually comment about why media feel that doctors being paid for legal work with industry constitute a conflict, NYT posed the question: “why are journalists and ethics boards so quick to assume that money, particularly corporate money, is the first factor to look at when evaluating someone’s work?”

As the article accurately describes, journalists are “lazy,” and would rather try and tie money and corporate connections than “analyze all the other factors that can bias researchers’ work: their background and ideology, their yearnings for publicity and prestige and power, the politics of their profession, the agendas of the public agencies and foundations and grant committees that finance so much scientific work.” Such difficulty in the field of journalism is not monitored by any well followed or nationally recognized code or standards.

Application to Medicine

Some critics of work with industry such as The Journal of the American Medical Association made it a requirement that any published had at least one author with no ties to the industry who would formally vouch for the data. When the author in question works with a totally different company or on a different kind of drug or study, or multiple companies, why should this matter?

The weaknesses of this approach were quickly addressed in BMJ (formerly The British Medical Journal), “which analyzed dozens of large-scale clinical trials in previous decades and reported that industry-sponsored ones met significantly higher standards than the nonindustry ones.”

Another unintended, yet harmful consequence is that these so called ‘conflicts’ are scaring away “the best medical researchers and causing them to shun drug company money altogether — not because they think it leads to bad research, but because they are tired of that fact being highlighted every time they are identified in a news story, as if that were the most important thing to know about their work.”

In fact, NYT even asserted that “too often, corporate conflict-of-interest accusations have been used as smear tactics to silence scientists who ended up being correct. (Go to nytimes.com/tierneylab for examples.)”

Ultimately, as the author suggests, journalists should simply list a link to a page where scientists can list all their public and private donors, “and let readers decide which ones are potentially corrupting.” Moreover, conflicts that should be reported should be relevant, not a financial life story.   

We agree with Dr. Pachauri: “follow the science, not the money,” because that’s what will help physicians treat patients and make people healthier.

JACO: Researchers Contributions and Ties with Industry

A recent study in the Journal of Oncology titled “Relationships Between Authorship Contributions and Authors’ Industry Financial Ties Among Oncology

Clinical Trials”, tried to determine whether authors who play ‘key’ scientific roles in oncology clinical trials, are more likely than those who do not play such roles to have financial ties to industry.   The finding was simple, the most productive authors (those who wrote the most papers, did the most studies) benefited from industry support.

In other words, the study tried to determine whether doctors who do work get paid for their work.

Research Findings

Of the 235 articles reviewed, 52% reported industry funding, 42% reported government funding, and 24% reported foundation funding.

Only twenty-nine percent of authors reported at least one financial tie to industry. The most common areas of funding were (12%), honoraria (11%), and consulting (10%).

Among industry-sponsored trials, 669 (44%) of 1,518 authors reported at least one tie to a commercial entity. Of these, 94% reported at least one tie to the study sponsor. Among authors of non–industry-sponsored trials, 173 (12%) of 1,409 reported ties to a commercial entity.

The research found that sixty-four percent of the authors -- 1,881 of 2,927 -- said they performed at least one key role in the study.

The study found that such researchers “who design clinical trials, analyze or interpret the data, or play other key scientific roles are four times more likely to have financial ties to industry than their counterparts who have lesser roles in these studies, such as recruiting study subjects or collecting the data.”

Limitations

The study was limited because the data were derived from articles published in a single oncology journal during a limited time between January 1, 2006, and June 30, 2007.

The data on financial ties and on authorship contributions from the study were also limited because they were self-reported, which could lead under- or over-reporting of financial ties, or of inaccurate reporting of authorship contributions.

Another limitation included the possibility that multiple instances of authorship by an individual author could have influenced the results.

In addition, the authors acknowledged that “the data do not directly address the causal mechanisms underlying the observed association between authorship contributions and financial relationships.”

Discussion

The problem with this type of investigation is that it can be misconstrued despite the fact that the collaboration provides benefits to patients. The paper assert that “cancer researchers who have the greatest ability to influence research are also the researchers with the greatest financial ties to the pharmaceutical and biotechnology industries.”

Instead, the recent JCO article suggests that these financial relationships have the potential to bias the outcome of such clinical research, even though patients are improving.

Such a suggestion harms patients, physicians and researchers because it stigmatizes important research and clinical testing on cancer drugs bases on the “potential for bias.”

But even Dr. Harlan Krumholz of Yale University, noted that "In some cases, industry-physician relationships may represent high integrity interactions between industry and academic scientists seeking knowledge about the effect of a treatment on patients. 

Another reason why the media and the authors of this article need to reconsider their claims for potential bias is because “not all types of relationships between researchers and companies are of equal concern,” according to Dr. Bernard Lo, director of the program in medical ethics at the University of California at San Francisco.

For example, speaker’s bureaus, consultation, and clinical trials play totally different roles in the type of experience and value physicians and researchers gain, and the amount paid is also different.

  

Journals accommodating this kind of survey non-research as scholarship, downplay the value of industry association, and allow the authors to cite only the alarmist background is extremely problematic. Moreover, the recent JCO article only displays how “disclosure” is heavily abused.

Editorial

In response to the study, an editorial “Authorship and Industry Financial Relationships: The Tie That Binds” was also published in JACO, which noted that “collaborations between physicians and drug companies clearly benefit society, as evidenced by the remarkable advances we have witnessed in cancer research in just the past few years.”

The authors of this editorial however try to downplay such collaborations by citing an Institute of Medicine (IOM) report that “concluded that such conflicts present the risk of undue influence on professional judgments and thereby may jeopardize the integrity of scientific investigations, the objectivity of medical education, the quality of patient care, and the public’s trust in medicine.”

The evidence for this ‘risk of undue influence’ is minimal at best because as the editorial states, “all authors must now report their contribution to a study’s conception and design; financial support; administrative support,” and other factors. Moreover, the editorial itself states that what Dr. Steven Joffe and other authors found “is perhaps not at all surprising given that most physicians in the United States have a financial relationship with industry.”

This relationship with industry is crucial for cancer research, patients and physicians because the vast majority of the clinical trials are pharma sponsored because the universities cannot afford to do investigator initiated trials. 

In addition, phase III and registration trials are overwhelmingly carried out by private companies, and more than 80% of medical oncology is private practice. With numbers like that, where do these authors suggest getting funding for trials on new cancer drugs, resources to recruit patients, and physicians who are willing to dedicate there valuable time for free?

Conclusion

The JCO study on relationships with industry stated clearly that:

    “There is a lack of solid empirical data to determine if, on balance,    relationships between physicians and industry ultimately harm or   benefit society.”

Accordingly, the idea suggested by authors in the editorial and article that disclosure is not enough, must realize that “there are a number of ways to minimize conflicts of interests including removal, recusal, third-party evaluation, codes of ethics, and disclosure.” In fact, the American Society of Clinical Oncology guidelines, published in 2003, rely heavily on disclosure as the principal method of dealing with perceived COI.

The fact that “author disclosures are becoming increasingly complex and there is not a uniform system for the disclosure of financial information,” does not translate into a conflict for doctors who work with industry. Specifically, the article noted that although researchers are associated with industry sponsorship:

    “little is known about the relationship between investigators’ personal financial ties and study outcomes.”

Moreover, the article “states that the data does not prove that authors’ financial ties are problematic, nor do they necessarily reflect efforts by sponsors to influence investigators’ work."

Without such data, cancer research in collaboration with industry should be continued and strengthened, especially when the JCO article stated that “most patients in cancer-research trials were not worried about financial ties between researchers or medical centers and drug companies and would still have enrolled in the trial if they had known about such financial ties.”

In the end everyone may benefit one day from improved cancer care, even the authors.

JAMA Mild Depression Meta Analysis Unraveled in the New York Times

 

A recent study published by the Journal of the American Medical Association (JAMA), questioned the effectiveness of antidepressant drugs. The research found that although drugs are “useful in cases of severe depression, those with mild to moderate cases, the most commonly used antidepressants, are generally no better than a placebo.”

According to Richard Freidman, MD, professor of psychiatry at Weill Cornell Medical College such findings are contrary to the evidence found in “hundreds of well-designed trials, not to mention considerable clinical experience, showing antidepressants to be effective for a wide array of depressed patients.”

As a result, a New York Times editorial asserted that the published study did “not stand up to a mountain of earlier evidence,” because of the way it was conducted.

The JAMA study was not based on clinical trials but instead, combined analysis of previous studies. While using this type of approach has the potential to discover drug effects that may have been missed in smaller studies “by aggregating the data from many studies and detecting broad patterns” from statistical information, this approach also has problems.

For example, with hundreds of studies on antidepressants, how did the JAMA researches decide which studies to use?

According to NYT, JAMA “authors identified 23 studies (out of several hundred clinical trials) that met their criteria for inclusion. Of those 23, JAMA could get access to data on only 6, with a total of 718 subjects. Three trials tested the antidepressant Paxil (a selective serotonin reuptake inhibitor, in the same class as Prozac) and three used an older drug, imipramine, in the class known as tricyclics.”

With such a small number of subjects being used for the study, and little access to data, it should come as no surprise that even one of the JAMA study’s authors, Robert J. DeRubeis, a professor of psychology at the University of Pennsylvania, noted that the results from the study cannot be “generalized to other medications.”

Another weakness in the JAMA study was that “the authors of the new analysis decided to exclude a whole class of studies, those that tried to correct for the so-called placebo response.” Consequently, in neglecting this group from their research, JAMA authors “showed a comparatively small average difference between drug treatment and placebo treatment,” a result that would have been different if they had included this group in their analysis.

In fact, if JAMA had used “randomized clinical trials that try to correct, or wash out, the placebo effect,” the authors would have probably seen “patients with mild to moderate depression respond to antidepressants at rates nearly identical to patients with severe depression (who tend to have a much lower response to placebos).”

In addition to these limitations, the JAMA study is problematic because it based its conclusions on only two antidepressants — when there are 25 or so on the market. How the results from this study could be used to generalize a whole class of medicine is shocking considering “the Food and Drug Administration investigated the safety of antidepressants by analyzing data from some 300 clinical trials, with nearly 80,000 patients, involving about a dozen antidepressants.”

Ultimately, while science and “landmark study’s can come along and overturn ideas about a particular treatment,” the JAMA study does not. Their weak reliance on small amounts of data, too few drugs and patients, and methodology should discourage no one from taking their antidepressants, because the continued use of antidepressants is crucial for millions of patients in preventing relapse, and reducing symptoms.

JAMA authors from this study should acknowledge the limitations of their research cited here, and consider a way to inform the public about making the right decisions about antidepressants based on “solid scientific evidence,” rather then a small sample.  

The editor should consider that scaring the public into not taking their medication is bad medicine!!!!

 

Study Shows Overwhelming Majority of Journals Track Relationships with Authors

A recent article in the Journal of the American Medical Association (JAMA), titled “Requirements and Definitions in Conflict of Interest Policies of Medical Journals,” examined the COI policies of medical journals to determine the prevalence and variability of COI disclosure requirements and definitions.

 

The article noted that “recent studies examining the content of COI policies among journals with a clinical focus are limited,” and there is “variation between journals in handling information about COI.”

 

According to the report; an overwhelming majority (89%) of medical journals have readily available on-line COI policies and require submission of COI statements.  Those remaining 11% without online COI statements in all likelihood have COI policies, just not readily available for review.    

 

This represents a major change in collecting and disclosing COI by medical journals.  A 1997 study found only 16% of medical journals had COI policies in place as compared to 89%+ today.

 

All high impact journals have COI policies and procedures in place.

 

Research Findings

 

The study identified 2117 medical journals across 35 subject categories, with 262 journals from these 35 subject categories being used.

 

Of 262 journals, 256 (98%) provided a URL linking to Instructions for Authors, manuscript submission forms, or both.

 

Within the Instructions for Authors, 25% of journals included online links to policy statements or articles on COI.

 

The study found that 228 of 256 sampled journals (89%) had language requesting author COI disclosure, and 89% of medical journals also had COI policies available for public review. Of the 89%, eighty five percent of journals requested COI disclosure in the Instructions for Authors, and an additional 4% requested COI disclosure only in manuscript submission documents. Of 256 journals, 138 (54%) required authors to submit signed disclosure statements.

 

77% of the journals defined or gave examples of possible COIs for submitting authors, and most of these journals included direct financial relationships such as “equities interest or stock ownership” (89%) or “consultancies” (84%). A minority included other potential conflicts such as personal relationships (42%), paid expert testimony (42%), relationships with organizations (26%), or travel grants (12%).

 

All internal medicine, respiratory medicine, and toxicology journals studied had comprehensive COI definitions, with 19 of these 24 journals requiring signed disclosure attestations.

 

6 of the 19 highest-impact journals in geriatrics and gerontology; radiology, nuclear medicine, and medical imaging; and rehabilitation requested that submitting authors disclose COIs.

 

Another survey (published in 2006) of the editors of 91medical journals found that 93% of medical journal editors reported having a COI policy.

 

Conclusion

 

In 2008, most medical journals with relatively high impact factors had author COI policies available for public review, although there was substantial variation in journal policies for solicitation of author COIs and in definitions of COI. 

 

The study was limited because the authors did not survey the journal editors, and relied on review of journal policies available on the Internet. As a result, the authors noted that their “methodology could lead to underestimation of the prevalence of COI policies if COIs were only requested by editors in communication with authors after submission.”

 

Additionally, the research found a lack of uniformity among journal editors on what constitutes COI, highlighting the difficulty authors encounter as they submit to different journals may limit the intended goal of COI policies. As a result, the article mentions the recent work of the ICMJE and editors of leading medical journals who have implemented increasingly comprehensive policies regarding disclosure of authors’ financial interests and other potential conflicts. Consequently, they even asserted that “conflict of interest policies and their implementation have evolved over time,” which led the study to conclude that journals have experienced “a substantial increase in the prevalence of COI policies over the past decade,” an “encouraging finding.”

 

Another factor that has led to this increase in COI policies in journals is that ICMJE member journals have recently published a uniform vehicle for recording and submitting COI disclosures. Although this new uniform disclosure form has standard definitions and disclosure requirements and enables authors to save online copies of the forms that can be updated as needed, ICMJE member journals are still testing this form and the universal disclosure process and are asking for feedback until April 2010.

 

Once journals and ICMJE members are able to gather enough information about the effectiveness and drawbacks of this form, journals will hopefully be able to eliminate the need to reformat disclosure information for each submission to ICMJE member journals and other journals that would eventually accept this universal disclosure form.

 

Ultimately, this JAMA study is an encouraging piece or research revealing the recent trends in journals, editors and articles habits of disclosing information and reporting potential COIs. The future transparency among companies, researchers and physicians in the coming months will only continue this trend to help certain media sources and officials realize that authors and editors of journals maintain high levels of integrity when disseminating research breakthroughs to the public.

Interventional Cardiologist Speaks out on Work with Industry

A recent article in the Journal of Health Care Contracting tried identifying problems with conflict of interest regarding speaking and consulting for industry, by focusing on two specific questions: first “how susceptible are physicians to being influenced to purchase products or equipment, or prescribe certain drugs, based on their relationship with a vendor and the freebies or consulting/speakers’ fees they receive? And second, do physicians, in fact, make purchasing or prescribing decisions based on relationships rather than on the merit of the product or drug?”

In response to the first question, the article provided that physicians are not influenced because most drug and device makers such as the Advanced Medical Technology Association (AdvaMed) and Pharmaceutical Research and Manufacturers of America (PhRMA), already have “spelled out model codes of conduct for their members, proscribing certain practices, placing limits on gifts, etc.” Additionally, “many professional societies and associations, including the American Medical Association, also have codes of conduct or ethics in place,” which make it highly unlikely that any relationships influence purchasing or prescribing decisions.  

This kind of evidence was also emphasized by the Association of Clinical Researchers and Educators, or ACRE, who held its charter meeting in Boston last July. The article cites that “ACRE (www.acreonline.org) is an organization of medical professionals who recognize that appropriate physician-industry collaborations and relationships benefit patients and advance science."

Accordingly, the article noted comments from ACRE steering committee member Carey Kimmelstiel, M.D., director of cardiac catheterization laboratory and interventional cardiology, and director of clinical cardiology at Tufts Medical Center in Boston. He is also an associate professor of medicine at the Tufts University School of Medicine.

As Dr. Kimmelstiel asserted, today’s efforts to eliminate conflicts of interest have gone too far because the practices about which people are concerned - such as gift-giving, nice trips, etc. - have pretty much been eliminated. He also noted that rules reimbursing physician practices for talks are tight as well, probably too tight.

For example, when Dr. Kimmelstiel tried giving a presentation on a drug recently, he wanted to add some slides to his presentation to share his clinical experience with others but, he was unable to since the presentation had already been reviewed by the FDA and no changes could be made.

Essentially, the point Dr. Kimmelstiel was trying to make is that “most physicians are savvy enough to be able to ferret out those who are giving a talk of value vs. those who are prostituting themselves.” Moreover, the idea that a physician is going to change their practice patterns or be influenced by what they prescribe by Post-It notes or pens they use is problematic.

As a result, Dr. Kimmelstiel acknowledged that these “overly strict conflict-of-interest policies can stand in the way of the education of students, physician trainees and practicing physicians.” He noted that “groups of fellows and physicians gather on a regular basis to listen to cases and share knowledge on particular medical topics at local restaurants which are often subsidized by industry.” Since new guidelines will prevent this, he wondered "Who will fund them, since hospitals and state government will not.”

Dr. Kimmelstiel also indicated that stricter conflict of interest policies could “potentially spell an end to clinical research being carried out at hospitals.” He even cited how some companies are leaving states like Massachusetts for other states, where they do not have to spend time worrying about compliance and exposure.

In the end, Dr. Kimmelstiel asserted that since “physicians need ongoing education on new technologies and pharmaceuticals, the best people to provide that training are other physicians.” Consequently, physicians who provide such training are not ‘promotional speakers’ because the only thing they are promoting are their patient’s health. What Dr. Kimmelstiel calls it is ‘industry-funded speaking.’ The only way to give physicians the training about new technologies, clinical guidelines and clinical trials is to conduct educational sessions, which physicians should be paid for. Why would a physician take the time to do it for free? Why would any profession?

What Kimmelstiel and ACRE want regarding conflict of interest policies are "to begin to level the playing field, to begin to have a discussion so we don’t stop doing clinical research, so we don’t stop educating our peers and others." In order to carry out this discussion, "there are no way physicians and CME can survive without industry."

Researchers vs. Plaintiff Witnesses - The Credibility Gap

A recent article in the Chronicle of Higher Education focuses on an Ex-Merck Spokesman Pointing the Finger at Paid Consultants in Drug Lawsuits. The issue was discussed following an 11-page essay by Laurence J. Hirsch, a former spokesman for the pharmaceutical maker Merck & Company, which was published by the journal Mayo Clinic Proceedings, along with a supporting editorial by William L. Lanier, the publication's editor in chief.

Specifically, Drs. Hirsch and Lanier posed the question whether “journals also see a financial conflict when the researchers are being paid to help warn consumers against buying a potentially unsafe drug or medical device?”

“As examples, Dr. Hirsch cites Harlan M. Krumholz, a Yale University professor of medicine, who has collected some $200,000 while working on behalf of plaintiffs suing Merck, and David S. Egilman, a clinical associate professor of family medicine at Brown University, whose court testimony has brought him more than $2-million.”

Dr. Hirsch asserted in his article that “medical journals should be just as wary of Drs. Krumholz and Egilman as they are of company-paid researchers.” He further asserted that "It strains credulity that such consultants can be objective in depicting the behavior of the defendant they are being paid to help plaintiffs' attorneys sue," he said. As a result, industry representatives applauded Dr. Hirsch’s assertion.

For example, Ronald Rogers, a current spokesman for Merck noted that financial biases do not only come from industry expense accounts. He further asserted that Dr. Hirsch’s article correctly pointed out that "The pharmaceutical industry is being held to a higher standard than other groups.”

In response to Dr. Hirsch’s claims, Dr. Krumholz and Joseph S. Ross, an assistant professor of medicine at Mount Sinai School of Medicine also cited by Dr. Hirsch, claimed that his article did “not present any evidence beyond hearsay to support his assertions or contradict our findings." Interestingly, proponents of industry funded research usually assert the same thing: there is no evidence that industry support biases the outcome of research, articles or presentations. So who do we believe more, those who step on the stand and are specifically advocating one position, or those in the labs testing out science?

Other ‘comebacks’ that Dr. Hirsch’s article was biased were easily disputed by Dr. Lanier who noted that the article “makes clear Dr. Hirsch's past and present ties to Merck, and saying the publisher has no control whatsoever over editorial content.” Instead, Dr. Lanier noted that other “leading medical journals have consistently shown an anti-business bias that eventually will stifle the "creativity and productivity" of U.S. companies and force research and development abroad.”

As a result, Dr. Lanier hopes that “Dr. Hirsch's article would make fellow medical journals more skeptical of the financial motives of all authors,” because “tougher conflict-of-interest rules might just give honest researchers more paperwork and simply prompt any less-than-honest researchers to work harder to find loopholes.”

Accordingly, holding the pharmaceutical industry to a higher standard than expert witnesses called by attorneys is problematic. Looking at the whole picture, paying someone to advocate a certain position for an intended outcome has the potential for bias. When doing so involves convincing 12 people, the chance for influence is more subjective whereas, trying to convince science is largely based in the facts.

By shedding some light on the alternative perspective of conflicts, Dr. Hirsch’s article serves as an example that while everyone has an interest, and some have the potential for conflict.  Why are plaintiff physicians being treated differently than clinicians and researchers?

International Society for Medical Publication Professionals – Good Publication Practices Guidelines Released

The International Society for Medical Publication Professionals (ISMPP) recently published a revised Good Publication Practice document known as “GPP2,” which was developed in a Steering Committee, and independently peer reviewed and published in the British Medical Journal (BMJ). The goal of GPP2 was to address legislative, guidance, and ethical developments since 2003, and to reinforce the aims of the original document. The good practice publications guidelines were also updated in response to changes in the environment in which authors, presenters, and other contributors work together to communicate medical research. ISMPP noted that these guidelines apply to peer reviewed jour­nal articles and presentations at scientific congresses.

 

The new guidelines address how medical research is often the “product of collaborations with other individuals (such as clinical investigators, biostatisticians, and professional medical writers) from around the world.” Sometimes, these individuals work for pharmaceutical and drug companies. As a result, ISMPP recommends that companies describe obligations for good publication practice in written publication agreements with authors of articles or presentations and with members of writing groups or publication steering committees. ISMPP also recommends that authors:

 

· Avoid premature publication or duplicate publication;

· Disclose potential conflicts of interest in all articles and presentations;

· Identify funding sources in all articles and presentations including all significant contributions made by individuals and organizations;

· Ensure authorship is attributed appropriately; and

· Provide the sponsor with copies of publication policies from the authors’ institutions

 

ISMPP also recommends that the written agreement confirms the shared responsibilities of all contributors, including authors and sponsors, and that it:

 

· Confirms that sponsors will work with clinical investigators, authors, and contributors to report and publish studies in a timely and responsible manner;

· Defines the criteria that will be used to determine authorship for articles and presentations; and

· Provides protection to parties with intellectual property rights, and establishes a reasonable period before study results are made public for intellectual property rights to be protected

 

The new guidelines also recommend that written agreements for articles and presentations from research studies are made at the earliest opportunity—for example, when the protocol is finalized.

 

ISMPP noted that it may be appropriate for companies to reimburse rea­sonable out of pocket expenses (for example, travel expenses) incurred by contributors or pay for specialized services such as statistical analysis. As a result, the details of this reimbursement must be disclosed. Also, they recommend that no honorariums are paid for authorship of peer reviewed articles or presentations.

GPP2 also recommends using criteria to determine which of the contributors to an article or presentation should be identified as authors. Specifically, they believe the criteria for authorship described in the International Committee of Medical Journal Editors (ICMJE) uniform requirements. The new guidelines acknowledge that ICMJE criteria allow assignment of authorship to individuals who have contributed to the analysis and interpreta­tion of a study but who may not have contributed to its conception and design.

 

The new guidelines also discuss using a “contributorship model” to remove ambiguity by describing what individuals participated in an article or presentation, and what their role was. ISMPP states that individual contributions to an article or presenta­tion that should be acknowledged include study con­ception and design, conceiving the idea for an article, conducting or managing a study, collecting data, per­forming statistical analysis, interpreting data, analyzing published literature, drafting a manuscript, critically reviewing a manuscript, and approving a manuscript.

 

There are also new guidelines for presentations that include an acknowledgment, even if not requested by the journal or congress, to describe:

 

· Author contributions;

· Contributions to the article or presentation from people who are not listed as authors;

· The role of the sponsor in the study and its reporting; and

· Funding sources, if any, for the research and for the article or presentation, such as for the work of a professional medical writer.

 

With regards to professional medical writers, GPP2 recommends that they should ensure that authors control and direct writing and that disclosures of funding, potential conflicts of interest, and acknowledgment of contributions are made. They clearly state that “professional medical writers are not ghostwriters,” and they even cite the Association of American Medical Colleges stating that “transparent writing collaboration with attribution between academic and industry investigators, medical writers and/or technical experts is not ghostwrit­ing.” Consequently, ISMPP does recommend that authors and professional medical writers working with authors use a published checklist to discourage ghostwriting.

 

The new guidelines suggest that professional medical writers must be directed by the lead author from the earliest possible stage (for exam­ple, when the outline is written), and all authors must be aware of the medical writer’s involvement. The medical writer should remain in frequent contact with the authors throughout development of the article or presentation, so that the authors can critically review and comment on the outline and drafts, approve the final version of the arti­cle or presentation before it is submitted to the journal or congress, approve changes made during the peer review process, and approve the final version before it is published or accepted for presentation. GPP2 does allow authors to delegate to the medical writer (or to an assistant) the administrative tasks associated with submitting the article or presentation to a journal or congress.

 

GPP2 recommends that authors disclose financial rela­tionships and non-financial relationships that could be seen as inappropriately influence or seem to influence professional judgment. They ask for these dis­closures in all articles submitted for publica­tion in peer reviewed journals, as well as in abstracts and posters submitted to congresses at the time of submission, if space requirements allow, and that they are included in oral presentations and posters at the time of presentation, regardless of whether disclosure is requested by the journal or congress.

 

ISMPP does state however that presently there is no universal standard applied by journals and congresses for disclosure of potential conflicts of interest. As a result, they recommend favoring greater, rather than lesser, disclosure. They also recommend that  companies, and the organizations or individuals working for them, document how pub­lications are initiated and developed. ISMPP wants documentation to be including:

 

· Agreements to participate in the writing process (for example, signed and dated letter, email)

· Details of intellectual input, direction, and contributions, including comments on drafts (emails, notes from teleconferences) or drafts that contain revisions

· Main versions of the draft, to document how comments on previous versions were incorporated

· Workflow and timelines that were used to develop the document, including time taken to review and revise the document

· Approval from authors of the final version to be submitted

· Lists of participants other than authors who were allowed to review or comment on the document.

 

This update for publication guidelines will serve as a useful reference to researchers and authors for numerous medical journals and presentations.

Medical Journals: British Medical Journal: Is the Conflict of Interest Unacceptable When Pharmaceutical Companies Conduct Their Own Trials?

 

This week in point counter point articles in the British Journal of Medicine (BMJ) debated whether is the conflict of interest unacceptable when pharmaceutical companies conduct trials on their own drugs?

 

On the side of industry conducting their own trials is Vincent Lawton, healthcare consultant and non-executive director of Medicines and Healthcare products Regulatory Agency, London, argues that there is no conflict.

 

Ben Goldacre, a doctor and writer from Nuffield College, Oxford, argues that there is a conflict.  According to his website Bad Science, Dr. Goldacre is a award-winning writer, broadcaster, and medical doctor who specializes in unpicking dodgy scientific claims made by scaremongering journalist, dodgy government reports, evil pharmaceutical corporations, PR companies and quacks (this covers just about everyone but himself).

Dr. Goldacre believes that the financial interests of drug companies lead to distorted evidence, whereas Vincent Lawton believes that adequate safeguards exist to keep bias in check.

 

Vincent Lawton (No)

As Mr. Lawton asserts, “clinical trials are properly managed by a rigorous system of regulatory scrutiny throughout.” These trials are also carried about “by some of the best scientists in the world, often in collaboration with academic researchers.” Without such trials, the drug industry would not be able to develop medicines, which they have spent years doing research on and investing significantly in.

 

Mr. Lawton also noted the importance of clinical trials because they “are an essential part of developing safe and effective drugs, and after the drug is introduced to clinical use more is discovered about its effects.” Additionally, these trials “are done to provide further information and study whether new indications can be added to the drug’s use.”

 

Consequently, he defends the legitimacy of industry involvement in these trails because they “are assessed and endorsed by regulators who assiduously guard against inadequate trial design, insist on good clinical practice standards, and ensure high quality analyses.” Moreover, he explains how “ethics committees, who are fully independent, do not countenance a substandard study design, and frequently intervene before a study is allowed to proceed.” As a result, he cited specific evidence that ^“suggests that industry sponsored studies have higher methodological quality than those funded by other bodies.”

Regardless of these safeguards, Mr. Lawton does not discount the need to eliminate bias, and he notes that “industry has developed various transparency measures” by working with regulatory agencies for the design of studies. These transparency measures include publicly accessible databases that contain information regarding industry involvement.

 

Still, Mr. Lawton poses an important question: are these companies, who invest an average $1.2 billion and 10 years to bring a medicine to the market, supposed to surrender their intellectual property to a third party’s lack of infrastructure, expertise, and resources? Such a requirement he asserts “would inevitably lead to delays, cutting into patient access and the patent life of the medicine, which would be a sure way to drive away the incentive to innovate.”

 

Dr. Ben Goldacre (Yes)

Dr. Goldacre’s premise is that drug companies have a conflict of interest because “they want to sell their products, and so naturally they want a positive result from the trials they sponsor.” Supporting this claim, he asserts that “there is now good evidence … that this conflict of interest results in bad evidence, which distorts medical decision making and so harms patients.”

 

For example, he talks about how every single trial on non-steroidal anti-inflammatory drugs (NSAIDs) that compared one drug to another, the sponsoring company’s drug was either equivalent to, or better than, the drug it was compared to.

Another example he uses showed that 30 studies investigating the influence of industry funding found that studies sponsored by drug companies were more than four times as likely to have outcomes favoring the funder, compared with studies with other sponsors. Our question to Dr. Goldacre, is since more than 75% of funding for clinical trials comes from industry, where does he suggest the money come from?

 

He believes that funding creates a “questionable trial design” and that “industry can choose which data to publish, and which to leave unavailable.” He also asserts that publication bias can result from industry funding, which makes negative results disappear.

Consequently, he recommends that drug companies must demand “full mandatory publication of all trial data from themselves and their competitors.”

 

Dr. Goldacre however ignores the sources that Mr. Lawton sites by stating that regulators are failing to address these problems. As Mr. Lawton’s article notes, both industry and regulators are managing these potential conflicts through numerous safeguards such as independent ethics committees. The few examples that Dr. Goldacre use does not warrant the total transformation of the way clinical trials collaborate between academia and researchers that he calls for.

 

As a result, Mr. Lawton’s recommendation that companies must continue “to work closely with academia and regulators to identify weaknesses or shortcomings and find ways to address them” is more appropriate. In doing so, health care will “continuously improve,” and the competition and investment it creates will “drive innovation.”

British Medical Journal:  Is the Conflict of Interest Unacceptable When Drug Companies Conduct Their Own Trials?

Negative: Vincent Lawton

Positive - Dr. Ben Goldacre