Science in the Private Interest: Has the Lure of Its Profits Corrupted Biomedical Research? By Sheldon Krimsky
264 Pages • Rowman & Littlefield 2003
Does one serve science – and the pursuit of the truth – by appointing an expert to a federal panel that recommends marketing approval or disapproval for new drugs, even though this expert has numerous conflicts of interest, having served as a consultant to many companies and conducted clinical trials with similar and competing drugs? Or is it better to bring in the uninitiated, more naíve, less expert but less biased (usually younger) academician in the unlikely hope of obtaining an equally erudite opinion with more objectivity?
Should a journal editor choose a book reviewer who has written a similar book a decade ago – as has this reviewer – with the presumption that the reviewer will be more informed and better equipped to analyze the new book? Or is it better to have a less experienced reviewer who will not be influenced by his or her previously printed opinions, who can be more objective about the merits of the book? These questions are at the heart of issues raised by Sheldon Krimsky in his new book, Science in the Private Interest: Has the Lure of Its Profits Corrupted Biomedical Research?
Science in the Private Interest is, first of all, a scholarly treatise and well referenced – reflecting the author's professional diligence and years of study. Two decades ago, Dr. Krimsky began publishing books on the social aspects of biomedical research; he is clearly an expert in the field. The author does not deal with the conflicts in academia that arise from the search for fame, but confines himself to those of pecuniary origin.
‘DEGRADATION OF THE ACADEMIC SCIENTIST’
The fundamental thesis of Dr. Krimsky's new book is best stated in his final chapter: “I have argued that the greatest danger we face from the unrestrained commercialism of our institutions of higher learning is the loss of supportive venues in which public-interest science and public intellectuals can thrive. … Public interest science includes the academic researcher's role as an independent voice of critical analysis on contested public issues involving his or her expertise.”
The major theme of this superb book, therefore, is the degradation of the academic scientist, who is lured to the pecuniary gains offered by industry and now asks the scientific questions posed by industry instead of independently pursuing scientific investigation of public needs. The author notes industrial funding in universities in the year 2000 ranged from 3.6 percent at Harvard to 31 percent at Duke (the average is about 15 percent).
Further, this analysis probably reflects total dollars received from industry. As clinical trials are expensive, in many cases the actual number of investigators receiving such funds is a small percentage of the university's research staff. Nevertheless, the author is correct in observing that the university now finds itself with a subset (at least) of academicians who are asking what the university can do – or permit – to enhance their financial status; less interesting to these investigators is how to pursue knowledge for its own sake or for the public interest.
In spite of gigantic increases in the NIH budget in the past few years, I do not see this subset of investigators changing their stripes in the near future. The answer is to maintain and expand public funding of public questions, and though we seem to be spending more money than ever to do this, I agree with Dr. Krimsky that the trend on this issue is troubling. In defense of this subset of investigators, virtually all would say that they make an enormous contribution to public knowledge and to public health. Nevertheless, the impact they have on our colleges and universities is uncertain.
Although the intellectual corruption of our best academic scientists is the author's major concern, he addresses other issues as well. Krimsky argues, for one, that industry-academic collaborations endanger science itself and that the truth-seeking effort fundamental to the university is compromised if academicians bend their scientific direction toward the goals of the company. Undoubtedly, a small number of clinical studies by a few individuals resulted in tainted scientific results and worse, have injured patients in the process. The author makes the clear observation: “A physician who supervises clinical trials must have no equity interests in a company that stands to gain or lose from the outcome of the trials.”
While this seems to ring true on its face value, there are two extremes of equity, which make enormous differences in the risk of conflict of interest. The academician-entrepreneur who has a majority of stock in his or her small drug company is very different from the similar clinical investigator who, instead, has 100 shares in a multibillion-dollar company, or shares in a mutual fund with pharmaceutical stocks.
The former is at great risk when controlling patient studies with the new drug, whereas the latter presents a minimal issue. In fact, most of the publicized cases of conflict of interest have come from small, tightly controlled companies, where oversight is minimal.
THE TRUTH-SEEKING PROCESS
By contrast, in large companies, a “chain of truth” is implicit – the toxicologist depends on the veracity of the basic pharmacologist, the clinical pharmacologist on the toxicologist and, ultimately, the clinical investigator relies on the truthfulness of the clinical pharmacologist. The result is a continuous truth-seeking process that characterizes the progression of a drug in the research and development departments of big companies. Anything less than full scientific disclosure at each and every step is unacceptable.
Most universities now recognize the difference in risk between a single entrepreneur and an investigator in a large, industry-sponsored multicenter trial; differing restrictions are appropriate. More to the point, industry is exceedingly anxious to conduct trials that will meet regulatory requirements, and strict monitoring by the company of the conduct of the trial at every clinical site, including the university sites, is universal. Any investigator who abuses the clinical protocol, for example, by admitting ineligible patients, is reprimanded or dismissed from the study. With notable exceptions, therefore, it is not clear that much damage is being done to the truth-seeking effort by academic-industry collaborations. In fact, the remarkable new medicines that have emerged in the past two decades strongly suggest that the collaboration benefits science and society.
MANAGING CONFLICTS OF INTEREST
Dr. Krimsky also addresses the newfound monetary gains that have been showered on biomedical academia – a concern that I think is coming under control. Both the American Association of University Professors and the Association of American Medical Colleges have published documents on how to manage conflict of interest in the university. Some say that such conflict cannot be managed, and that “management” is a euphemism for lack of control. I respectfully submit that this is not the case, and that proper controls (management) can be effected without strangling the investigator's flexibility. In fact, it is sad that the universities took so long to come to such obvious conclusions. The delay reflects the diffusion of authority in many universities, where the hierarchy has less than full control over the departments – an observation also noted by Dr. Krimsky – and where only a public relations disaster can force the needed action.
Finally, Dr. Krimsky addresses a proposal to create a national independent drug testing center, where only data from the center would be used to gain drug approval for marketing. Again, the face value seems quite good. Companies would pay money to a new center at the NIH, for example, and the trials would be contracted out to the required investigators by this new third party, the federal government.
I can attest from personal experience that there are numerous problems with this approach. For example, when I was Chief of the Epilepsy Branch at NINDS, I had a crack team of about 45 physicians, statisticians, and monitors to conduct clinical trials of new antiepileptic drugs. Clinical trial expertise in the academic epilepsy community at that time was minimal, but we contracted out four multicenter, randomized, controlled clinical trials (RCCTs) with four different drugs in less than three years – a substantial feat, and one for which I am quite proud.
Just ten years later, when I joined a large pharmaceutical company as head of clinical pharmacology, within six to 12 months a similar-sized team was writing protocols and contracting out more than one study a week! Although the latter studies were smaller than RCCTs, it is impossible to overemphasize how much more efficient private industry is in comparison with the government.
Because I think that neither science nor patients are abused by these companies – indeed both are highly protected – I cannot see any reason to create a monster multibillion-dollar government bureaucracy to replace the current clinical trials system. It would not even solve Dr. Krimsky's major issue – that is, it would not enhance the independence of the clinical trial academician because clinical trials would still have to be designed specifically for regulatory approval, and little investigator independence could be permitted.
Although I take issue with some of the author's conclusions, this is an academician's book, thorough and well-organized. It should be required reading for those who are in charge of scientific conflict-of-interest issues in our colleges and universities.