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RESEARCH ETHICS

Can We Bank on Objectivity?

Proposed NIH Rules Aim to Curb Influence of Industry Dollars

blank check made out to NIH-supported scientist for favorable findings from your industry funder SOURCE: AP/Gail Burton Managing financial conflicts of interest is a complicated policy matter, as researchers and their institutions often receive both public and private funding to support research that leads to new treatments. But research also indicates these conflicts are widespread and ingrained. How far should we go in addressing the issue?

Trust is the crown jewel of the research enterprise. Financial arrangements related to research that call into question the integrity of investigators or research institutions are damaging, not only because they may potentially harm research participants, but because they are associated with the appearance of impropriety. Either way, trust is compromised.

The National Institutes of Health recently published advanced notice of rulemaking and a request for comments concerning the responsibility of applicants for promoting research objectivity related to Public Health Services funding.[1] This push for more stringent regulation of financial conflicts of interest, referred to as COIs, is predictable, given the intense scrutiny Congress has placed on these financial conflicts.

Resources

The NIH proposed rules on conflicts of interest in the Federal Registrar.

P.M. Tereskerz, et al., “Prevalence of Industry Support and its Relationship to Research Integrity,” Accountability in Research 16(March-April, 2009):78.

But managing conflicts of interest is a complicated policy matter, as researchers and their institutions often receive both public and private funding to support research that leads to new treatments. The proposed rules provide much-needed guidance that has been lacking in the past and support greater disclosure and transparency. But they fail to address other complex matters, such as the route corporate dollars can follow through non-profit institutions and into the salaries of biomedical researchers. Further, my colleagues and I have conducted research demonstrating that financial conflicts are widespread, ingrained within the research infrastructure, and in some cases endanger the well being of research participants.

A recent Congressional investigation, led by Senator Chuck Grassley (R-IA), revealed several unfortunate failures to disclose financial arrangements by investigators. In one reported case, a highly influential Harvard child psychiatrist, Dr. Joseph Biederman, whose research contributed to the increased use of antipsychotic medicines in children, earned at least $1.6 million in consulting fees from drug makers from 2000 to 2007. However, he allegedly did not report much of this income to his university officials.[2]

In the months that followed, the investigation led to accusations that another prominent Emory University psychiatrist, Dr. Charles Nemeroff, received $2.8 million dollars from a drug company and did not report much of the income. At the same time, reports indicated that Nemeroff was overseeing a NIH study on five anti-depressants produced by the research funder, GlaxoSmithKline, between 2000 and 2007.[3]

These are but two of the more public cases identified as part of the investigation.[4] And, just as this piece was being written, there came news that a former Walter Reed Army Medical Center surgeon, who was a paid consultant for a medical device company, published a study allegedly containing false claims and overstated benefits of the company’s product.[5]

As with the individual cases uncovered by the Congressional investigation, this empirical evidence suggests that there is a gap between policy and practice.

Recently, my colleagues and I (including Science Progress Editor-In-Chief Jonathan Moreno) published a national study, funded by NIH through the Office of Research Integrity, on industry-sponsored research and research integrity which further illustrates the problematic nature of financial COIs, which inevitably attend partnerships between researchers and the private sector.[6]

Researchers and research institutions often receive both public and private funding to support their work. The majority of those we surveyed in our study who received industry support for research indicated that this funding was important to their research or publications. Yet, the more important the industry support was to respondents, the more likely they were to report first-hand knowledge of compromises in research integrity. And we found that knowledge of compromises in research integrity is widespread. Perhaps most alarming were respondents who reported first-hand knowledge that the well being of research participants was compromised because of industry sponsorship.

Other results from the study included first-hand knowledge of compromises in research initiatives (35 percent), publication of results (28 percent), interpretation of research data (25 percent), and scientific advancement (20 percent) in all cases because of industry support. Also of concern was that industry-supported research occurred more often among the most senior and prolific researchers, those who no doubt are more likely to be leaders in their fields and have the ability to influence young trainees. Our findings follow many earlier studies that have raised concerns about the undue influence of industry sponsorship on research.[7]

As with the individual cases uncovered by the Congressional investigation, this empirical evidence suggests that there is a gap between policy and practice, signifying that current regulatory measures to manage financial COIs are not sufficient to manage the public/private partnerships that have been an important component in the acceleration of translational research from bench to bedside.

Cases emerging from the Congressional investigation and data emerging from studies point to areas upon which there is need for much greater scrutiny, and the proposed rulemaking makes important strides in addressing some of the limitations of the current regulatory scheme. For example, current federal regulations do not provide specific guidance on managing COIs that involve projects supported by the Small Business Administration’s Small Business Innovation Research Program or the Small Business Technology Transfer Program, with the exception that support for Phase I clinical trials is excluded from COI regulations.9 Yet, there has been a substantial increase in NIH SBIR/STTR awards in recent years, but the institutions receiving the funds are responsible for managing COIs.10 SBIR/STTR programs are set aside programs of federal agencies’ extramural budgets to provide funding for domestic businesses to undertake research and development that has potential for commercialization. Often this involves partnerships between academia and industry, and in the case of STTR’s this is required.

In 2002, NIH requested that 300 of those institutions provide a copy of their policy on COIs and reviewed a representative sample of over 100 policies. At that time, 96 percent of the policies did not mention SBIR programs in the policy document. It is ironic that some of the most complex and difficult financial arrangements emerge with SBIRs/STTRs, yet circumstances specific to these COIs are afforded little to no federal guidance for identification and management. Clearly, this is an area that needs to be addressed.

Importantly, the NIH’s proposed rulemaking identifies additional areas where guidance has been lacking and is urgently needed. For example, the notice questions whether the new rulemaking should include required education of investigators, independent assurance of institutional compliance with the regulations, enforcement mechanisms, and the need to address institutional conflict. Articulated guidance in these areas, establishing effective regulatory requirements, would be an important step forward.

The proposed rulemaking also includes consideration for expanding the scope of the regulation and disclosure of interests and questions whether all financial interests should be disclosed, in contrast to current regulations that require disclosure when the money involved reaches certain threshold levels. No doubt the threshold levels for disclosure are arbitrary. But to require reporting of any financial interest may be unduly burdensome on institutional administrations.

While many of the matters under consideration for expanding the regulations are necessary, they may not be sufficient. The proposed rulemaking does not seem to take into account opportunities for circumventing the intent and spirit of the proposed rules.

For example, the proposed rulemaking appears content with excluding salaries that are remuneration from one’s own research institution. There are researchers whose institutions have had research contracts with a given industry sponsor for years, and this funding is used to support the researcher’s salary year in and year out. Clearly, it is not lost on the researcher as to who is floating the boat. This means that the opportunity for influence and developing loyalty to an institutional underwriter still exists, even if the money paid to the investigator comes in the form of an institutional salary. Does passing the funds through the research organization remove the conflict of interest or just keep it out of public view? These pass-through arrangements may be particularly egregious because of their lack of public transparency. Further, these conflicts may reach beyond the investigators to the institutions themselves, since research contracts with institutions typically provide indirect funding for the institution.

Likewise, financial interests from seminars, lectures, or teaching engagements, or service on advisory committees sponsored by public or non-profit entities are excluded from disclosure requirements. Again, the problem is that many for-profit companies can create non-profit foundation counterparts and have funds filtered through these entities to bypass the language of the rules.

The proposed rulemaking is grounded in the need for transparency. Complete transparency of any financial arrangement that has the potential to compromise research integrity should be absolutely required. But it should be necessary only for those conflicts that cannot be avoided in the first place. Disclosure can only do so much and won’t cure a moral wrong.[8] Emphasis should focus on preventing, rather than managing, COIs in research, whenever possible. And, to a limited extent, the proposed new rules suggest this by asking whether investigators involved in participant selection, informed consent, and management of a trial should be prohibited from having a significant financial interest.

But in some instances collaboration between investigators and industry is necessary for innovation to move forward. The example that comes to mind is in the development of medical devices. So overall the challenge remains the same—how do we continue to encourage public/private partnerships so that translational research can continue to move forward at a rapid pace without compromising research integrity?

Perhaps it is time to think outside of the box and consider completely new models to better avoid COIs in the first place. This may require some major changes in how we go about the business of underwriting privately sponsored scientific research in this country. Some experts have proposed such models, but no one has seriously pursued them.[9] The Obama administration puts a premium on research integrity, possesses the intellectual acumen to embrace creativity, and has the courage to promote change. So the time is ripe to challenge experts to devise new ways to encourage public/private partnerships but simultaneously shield research objectivity from financial conflicts of interest. It will not be easy, but it can be done.

Patti Tereskerz, JD, Ph.D. is an Associate Professor, Research and the Director of the Program in Ethics & Policy at the Center for Biomedical Ethics and Humanities at the University of Virginia School of Medicine.

Notes

[1] Department of Health and Human Services, “Responsibility of Applicants for Promoting Objectivity in Research for Which Public Health Service Funding Is Sought and Responsible Prospective Contractors,” request for comments, Docket No. NIH-2008-0002, RIN 0925-AA53, Federal Register, 74 (No.88) May 8, 2009, pg. 21610.

[2] Harris, G. and Benedict, CA., “Researchers Fail to Reveal Full Drug Pay,” The New York Times, June 8, 2008.

[3] Akre J., “Million Dollar Conflict-Of-Interest By Emory Psychiatrist Uncovered By Grassley,” available at http://www.uslaw.com/library/Personal_Injury_Law/Million_Dollar_ConflictOfInterest_Emory_Psychiatrist_Uncovered_Grassle.php?item=259739 (last visited May 13, 2009); Harris G., “Top psychiatrist didn’t report drug makers’ pay,” The New York Times, October 3, 2008.

[4] See http://thomas.loc.gov/cgi-bin/cpquery/13?&sid=cp1111Nlmz&l_f=1&l_file=list/cp111cs.lst&hd_count=50&l_t=14&refer=&r_n=sr013.111&db_id=111&item=13&sel=TOC_195021& (last visited May 21, 2009).

[5] Wilson D. “Doctor Falsified study on injured G.I.’s, Army says,” The New York Time, March 12, 2009.

[6] Tereskerz PM, Hamric AB, Guterbock TM, Moreno J., “Prevalence of industry support and its relationship to research integrity,” Accountability in Research 16:78-105, 2009.

[7] See, for example, Bekelman Justin E, Li Yan, Gross Cary P., “Scope and impact of financial conflicts of interest in biomedical research: a systematic review,” JAMA (January 22, 2003), 289(4):454–465; J Lexchin, LA Bero, B Djulbegovic, and O Clark, “Pharmaceutical industry sponsorship and research outcome and quality: systematic review,” Br Med J (2003), 326:1167-1170; HT Stelfox, G Chua, K O’Rourke, AS Detsky, “Conflict of interest in the debate over calcium-channel antagonists,” N Engl J Med (1998), 338:101-106; RA Davidson, “Source of funding and outcome of clinical trials,” J Gen Intern Med (1986), 1:155-158; LA Bero, D Rennie, “Influences on the quality of published drug studies,” Int J Technol Assess Health Care, (1996), 12:2009-2037; M Friedberg, B Saffran, TJ Stinson, W Nelson, CL Bennett, “Evaluation of conflict of interest in economic analyses of new drugs used in oncology,” JAMA 1999, 282:1453-1457, LL Kjaergard, B Als-Nielsen, “Association between competing interests and authors’ conclusions: Epidemiological study of randomized clinical trials published in the BMJ (2002), 325:249.

[8] Katz J, “Informed consent to medical entrepreneurialism,” in Spece RG, Shimm DS, Buchanan AE, eds., Conflicts of Interest in Clinical Practice and Research, (New York, NY: Oxford Univ Press, 1996), 286-299.

[9] For some examples, see Tereskerz P., “Developing a new model: Preserving scientific objectivity, trust, and the informed choices of human subjects,” in Riding the Green Wave. Financial Conflict of Interest in Industry-Sponsored Clinical Research, Chapter 10, (University Publishing Group, Hagerstown, MD, 2007), pgs. 153-168; or Moses III H, Martin JB, “Academic relationships with industry: a new model for biomedical research,” JAMA (2001), 285:933.

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