Applied Clinical Trials
The public would be best served if both recognize their own questionable practices.
With so much attention during the past several years on the negative influences of industry on clinical research, one would think that all professionals employed and funded by pharmaceutical and biotechnology companies must be felons of the highest order.
Kenneth A. Getz
Widely covered investigations headed by Senator Grassley, daily allegations posted on the Internet, and statements from Marcia Angell and other outspoken critics suggest that any involvement in the clinical research enterprise by pharmaceutical and biotechnology companies must be tainted and motivated by greed.1-3
Responding on their own to growing pressures from politicians and the public, many academic institutions have been disclosing their physicians' business relationships with industry, no matter how trivial the amount. Early in 2009, several academic institutions jumped to distance themselves further: Harvard and Johns Hopkins, for example, announced much stricter limitations on faculty acceptance of speaking fees and gifts from industry. This past April, the Institute of Medicine (IOM) recommended that physicians sever all ties with industry.4
Colleagues in academia have raised numerous concerns about, and have documented, deceptive and unethical industry practices. Failures to disclose critical information about clinical trial results; distortions and exaggerations of the benefits of new interventions; and the pervasiveness of conflicts of interest that exist in physicians' relationships with industry are but a subset of the many questionable practices identified.
Taking things a step further, some colleagues are now calling for industry to have NO involvement in clinical research. They suggest that only academic-based professionals and those employed and supported by the National Institutes of Health are capable of ensuring probity.
This suggestion is naïve, bordering on delusional. Sadly, deceptive practices can be found throughout the clinical research enterprise. No stakeholder group is above repute and impunity. Guilt is evenly distributed.
In my 20 plus years as an observer of the clinical research enterprise, I have yet to meet a professional currently or formerly employed by academia and the NIH who doesn't possess deep frustration and concern with government-funded research programs and the politics and questionable practices associated with them. They are reluctant to speak out, however, fearing the harm it would bring their reputation and their career.
In fact, over the years there have been numerous scholarly articles and journalistic reports on a variety of questionable practices including academic institutions misusing and mismanaging federal research grants; unethical practices among professionals involved with government-funded clinical research; academic medical centers exaggerating and overstating the importance of their research studies; failure to disclose inspection results and serious adverse events among study subjects participating in NIH programs; compromised data reporting and misinterpretation of results; and the intense and unfair politics associated with grant applications and awards.5-10
Peer-review articles and media reports on deceptive industry practices have largely overshadowed those reports on questionable practices among academia and the NIH. But as industry is scrutinized and pressured to reform and improve its practices and behaviors, academia and the NIH must do the same.
Scholars and journalists have identified many potential and probable reform areas—some of these have been identified and touched on in this column. These are all areas requiring attention and, where necessary, remediation and reform.
With government spending in 2009 projected to exceed 44% of gross domestic product (GDP) and the Obama administration looking to optimize resources while pursuing ambitious health care reform initiatives, several colleagues have suggested looking closely at the inefficient use of federal clinical research funding. Specifically: How are tax payer dollars being allocated and how carefully are tax payer dollars being managed?
Poor financial controls in academia and the NIH, for example, are frequently cited by colleagues as an area most warranting attention. The media has uncovered many case examples over the years, and Senator Grassley's investigations are now shining more light on this area. In my review of published data from HHS and the Office of the Inspector General, I found numerous violations documenting grant recipients who have taken advantage of the NIH "honor system" of financial reporting.11
Problem areas appear to be most often related to cost transfers such as unallowable transfers and/or insufficient supporting documentation; failure to accurately capture the actual time and effort that staff have devoted to studies; failure to report financial conflicts of interest and questionable nonlabor costs charged to NIH grants such as lab equipment, and supplies that were purchased but not related to the research study.
During my participation on the clinical research roundtable at the IOM, several academic clinical researchers noted another area: the incidence of questionable and unnecessary research studies (i.e., studies that do not appear to merit NIH grant dollars and studies that do not appear to deliver actionable, useful results advancing medical knowledge and public health).
A May 20, 2009, report by a FOX news journalist represents a case in point. The report noted that the NIH is spending nearly $200,000 to investigate personal and cultural pressures on female and transgender prostitutes in Thailand. In my own cursory review of published data online listing funded NIH programs in 2008 across all institutes, I readily found examples of funded programs of questionable merit or that may have diverted funds away from more important and innovative research: a $75,000 annual grant looking at the impact of dragon boat racing on cancer survivorship, for example; a nearly $200,000 grant looking at soy almond bread as a complimentary therapy for prostate cancer; an annual $441,000 grant to study the healing powers of the canoe; a $261,000 grant looking at the risks facing female automobile drivers.
Several colleagues have suggested that federal funding may be going to redundant research grants awarded by the same or different institutes of health. They argue that government funding needs to be better coordinated.12
Taking a cursory look at the limited publicly available information from the NIH, I found it difficult to identify and discern similar or overlapping 2008 research programs. Still, a few examples raised red flags: $1.1 million in funding provided by different NIH institutes to three separate investigators at different universities, each looking at automobile-driver safety behaviors among the elderly; nearly $1.5 million awarded for three separate academic institutions to each study the prevention and treatment of lung injuries after chlorine exposure.
Similar to the conflicts of interest and greedy practices Senator Grassley and others have identified among physicians conducting industry-funded research, my colleagues insist that there is evidence suggesting that principal investigators (PIs) are doing the same in federally-funded programs.
The NIH has established policies setting salary caps for individual NIH grants; limiting a recipient's commitment to not exceed 100%; and requiring annual audits of organizations that spend in excess of $500,000 per year in grants. Still, my colleagues believe that there are loopholes due to poor financial controls that some academic PIs are exploiting to double and triple dip into the NIH grant pie.
From published sources online, it was easy to identify PIs, for example, who are receiving multiple grants from the NIH in 2008 that could conceivably have exceeded the salary cap. One investigator, for example, received 11 grants in 2008 totaling $3.1 million; another received nearly $5 million across five studies during that same period; and one PI received seven grants in 2008, across three separate NIH institutes, for $9.4 million. But in the absence of published information containing detailed budget data, it is difficult to determine whether, and the extent to which, select government-sponsored PIs may be gaming the system.
I am neither condoning, nor making excuses for, deceptive and questionable industry practices. And I certainly don't want to diminish the undeniable fact that the vast majority of professionals involved with both industry- and federally-funded clinical research are honest, compassionate and hard-working.
What I am suggesting is that academia and the NIH are far from bastions of integrity. They are fooling themselves and putting the clinical research enterprise at risk if they believe that questionable practices are solely industry's problem.
Academia and the NIH must proactively look within their own back yards, and identify and correct questionable behaviors across many fronts. Failure to do so will most certainly invite public and federal scrutiny and will, ultimately, result in the loss of public confidence and trust—sacred assets that the clinical research enterprise can ill afford to lose.
Kenneth A. Getz MBA, is a Senior Research Fellow at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, email: firstname.lastname@example.org
1. A. Mundy, "Pressured, Schools Review Ties to Drug Firms," Wall Street Journal, B2 (September 11, 2008).
2. S. Rubenstein, "Grassley Points to Another Academic Doctor's Industry Pay," Wall Street Journal, B3 (May 28, 2009).
3. M. Angell, "Drug Companies and Doctors: A Story of Corruption," The New York Review of Books, 56 (1) (January 15, 2009).
4. Institute of Medicine Report: Conflicts of Interest in Medical Research, Education and Practice, http://www.iom.edu/CMS/3740/47464/65721.aspx (National Academies Press, DC, April 28, 2009).
5. A. Shamoo, "The Need for Better Reporting of Adverse Events for Human Subjects in Research," DIA Today, 5 (2) 18-20 (April 2005).
6. E. Campbell, "Doctors and Drug Companies—Scrutinizing Influential Relationships," New England Journal of Medicine, 357 (18) 1796-1797 (November 1, 2007).
7. S. Woloshin et al., "Press Releases by Academic Medical Centers: Not So Academic?" Annals of Internal Medicine, 150 (9) 613-618 (May 5, 2009).
8. D. McCarron, "DASH-Sodium Trial: Where are the Data?" American Journal of Hypertension, 16 (1) 92-94 (January 2003).
9. N. Sung et al., "Central Challenges Facing the National Clinical Research Enterprise," Journal of the American Medical Association, 289 (10) 1278-1287 (March, 2003).
10. J. Levitz, "Yale's Use of Research Grants Attracts Government Scrutiny," The Wall Street Journal, A2 (July 5, 2006).
11. Violations identified through audits by the Department of Health and Human Services and the Office of the Inspector General, http://oig.hhs.gov/oas/nih_archive.asp
12. B. Wykoski, "As Universities Get Billions in Grants, Some See Abuses," The Wall Street Journal, A3 (August 16, 2005).