Wednesday, June 19, 2013

A Call to Restore the Integrity of Clinical Research - but Will Anyone Heed it?

Concerns about suppression and manipulation of clinical research to serve vested interests have finally gotten a little more mainstream.

Background: Suppression and Manipulation of Clinical Research

For a long time, we have decried and discussed examples of manipulation of clinical research done to increase the likelihood that its results would please vested interests, often drug, device or other corporations that sponsored the research and often exerted considerable control over its design, implementation, analysis, and dissemination.  We have also decried and discussed examples of suppression of research whose results offended such vested interest, sometimes done when manipulation did not succeed in producing such pleasing results.


I wrote about suppression of research in my 2003 paper on health care dysfunction,(1)

The integrity of medical research has been violated by the deliberate suppression of its results.

That assertion was based on several important, although understandably largely anechoic cases.

I first wrote about systematic attempts to manipulate clinical research in 2005, based on Richard Smith's PLoS Medicine commentary which listed specific tactics that vested interests could use to make it more likely that research studies would provide them with favorable results.

Although striking cases of manipulation and suppression appeared more frequently starting in the 1990s, in the last few years it has become more apparent that these are widespread problems.

A Call to Restore Integrity

This week, the British Medical Journal published a special article calling for restoration of suppressed or manipulated clinical trials(2), accompanied by an editorial entitled, "restoring the integrity of the clinical trial evidence base."(3)

The article used slightly different terminology than we do, replacing suppression with invisibility, and manipulation with distortion, thus,

Two basic problems of representation are driving growing concerns about relying on published research to reflect the truth. The first is no representation (invisibility), which occurs when a trial remains unpublished years after completion. The second is distorted representation (distortion), which occurs when publications in medical journals present a biased or misleading description of the design, conduct, or results of a trial.

The article boldly asserted

Both go against the fundamental scientific and ethical responsibility that all research on humans be used to advance knowledge and are symptomatic of a general culture of data secrecy. The end result is that the healthcare, biomedical research, and policy communities may, despite best intentions and best practices, end up drawing scientifically invalid conclusions based on only those parts of the evidence base they can see.

The editorial went further, asserting that

This crisis of hidden or misreported information from clinical trials—and the resulting distortion of the clinical evidence base—is widely recognized and commonly decried. It is one of the leading scientific problems of our time, but few solutions have been put forward.

Furthermore, it concluded with a warning about the immorality of continuing on the current course,

The results of clinical trials are a public, not a private, good. The public interest requires that we have a complete view of previously conducted trials and a mechanism to correct the record for inaccurately or unreported trials. If we do not act on this opportunity to refurbish and restore abandoned trials, the medical research community will be failing its moral pact with research participants, patients, and the public. It is time to move from whether to how, and from words to action.

Thus the notion that suppression and manipulation of clinical research is a systemic, severe problem that confounds health professionals and hurts patients is no longer a concern of only a few fringe dissidents, but a matter for discussion in the foremost mainstream medical journals.

Will Anyone Heed the Call?

Furthermore, this dire problem formulation suggests the need for a strong solution, as proposed by the article, and seconded by the editorial.  Using the term "abandoned trials" for " unpublished trials for which sponsors are no longer actively working to publish or published trials that are documented as misreported but for which authors do not correct the record using established means such as a correction or retraction (which is an abandonment of responsibility)," Doshi and colleagues wrote,

We call on institutions that funded and investigators who conducted abandoned trials to publish (in the case of unpublished trials) or formally correct or republish (in the case of misreported trials) their studies within the next year.

Starting in 2005, we have repeatedly called for protection of " researchers' rights to speak truth to power," but then noted that "right now, it is more often power that speaks to truth."  The question is whether without some bigger allies, individual clinical researchers will stand up on their own to restore the integrity of clinical research.

The big reason to worry is that most of these researchers work within a context which strongly favors vested interests, rather than scientific truth, or the rights of research subjects.  The researchers who would be most likely to be able to heed the call by Doshi et al are those within academic medicine. Yet clinical research in the academic medical world now functions within a strong and deep web of individual and institutional conflicts of interests, subjects that we also have written about incessantly.

There is evidence suggesting that the majority of medical faculty,(4) and the majority of their academic departmental leaders(5) have important financial ties to the health care corporations most likely to have reason to want to suppress or manipulate research.  Furthermore, most academic medical institutions have stated their interest in increasing "collaboration" with industry, usually giving the rationale that this will lead to "innovations" that will bring better tests or treatment to patients. (See posts herehere and here for some examples.)  Such collaboration also tends to bring a lot of money to institutional budgets.  Further collaboration with industry is likely favored by academic leaders' own financial ties to the same sorts of corporations discussed above.  Thus it should be no surprise that a study by Mello et al in 2005 suggested that most of the managers of academic medical institutions who control research contracts are willing to give significant control of of research design, implementation, analysis, and dissemination to the sponsors, not the researchers.  (See this post.) (6)


Thus, a researcher who volunteers to restore suppressed or manipulated clinical studies might become suddenly very unpopular with his or her colleagues or supervisors, and perhaps with people who are already paying him or her.

So as long as health care professionals, policy makers, and the public at large are willing to go along with the notion that academic medical institutions' "collaboration" with "industry" is absolutely necessary to foster "innovation" and hence medical progress, it is very unlikely that academic medical researchers will be willing to help restore the integrity of clinical research.  In fact, while we continue on our present course, the integrity of clinical research will probably get even worse.
 
Since questioning the integrity of contemporary clinical research might make those with vested interests who have been willing to suppress or manipulate research very uncomfortable, perhaps it should be no surprise that the paired articles in the British Medical Journal have been relatively anechoic.  For example, while one might think the publication of these simultaneous articles might get at least a little coverage in the "main-stream media," I can find not a single mention of them there.  (So far, only the Chronicle of Higher Education, MedScape the Science Insider blog and The Scientist blog have provided news coverage.)


So I hope the brave people who wrote the article and editorial are also willing to join us in decrying the web of individual and institutional conflicts of interest that have entangled health care professionals and academic medicine.  Individuals and institutions who make medical or health care decisions, or who are involved in medical and health care education and research should reveal all their conflicts of interest, at least in the interests of honesty.  Furthermore, in the interest of patients' and the public's health, clinical research meant to assess medical tests, treatments, and programs should be done completely independently from the corporations that sell them.  


References

1.  Poses RM.  A cautionary tale: the dysfunction of American health care.  Eur J Int Med 2003; 14: 123-130.  Link here..
2.  Doshi P, Dickersin K, Healy D et al.  Restoring invisible and abandoned trials: a call for people to publish the findings.  Br Med J 2003;  BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f2865  Link here.
3.  Loder E, Godlee F, Barbour V et al.  Restoring the integrity of the clinical trial evidence base.  Br Med J 2003;  BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f3601  Link here.
4. Campbell EG, Gruen RL, Mountford J et al.  A national survey of physician–industry relationships. N Engl J Med 2007; 356:1742-1750. Link here.
5. Campbell EG, Weissman JS, Ehringhaus S et al. Institutional academic-industry relationships. JAMA 2007; 298: 1779-1786.  Link here.
6.  Mello MM, Clarridge BR, Studdert DM. Academic medical centers' standards for clinical-trial agreements with industry. N Engl J Med 2005; 352:2202-2210. Link here.

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