Conflict of Interest (2002)

FigureIt's hard to concoct a research scenario in which the investigator does not desire one result over another. Perhaps some government-supported contract research would fall into this category—for example, an engineer paid by the Air Force to measure the tensile strength of several compounds, or a biochemist paid by the Food and Drug Administration to assess the bioactivity of two generic agents. But most investigators do care about the results—that's why they do the research in the first place. And that's why, on a regular, sometimes daily, basis your everyday working scientist comes up against the conflict between the desire to achieve a certain result and the obligation to uncover the truth. That conflict is an important part of the scientist's inner world, influencing every feature of the research endeavor from the question selected to the design, the methods of measurement, and the statistics applied in data analysis. An array of motives far too vast to enumerate lie beneath the desire to find one “truth” rather than another. Among the most powerful and ungovernable stands the desire for recognition. Less troublesome ones, however, are also at play. A “positive” result can bring a grant, the gratitude of a supervisor, and acceptance of the study for presentation at a meeting. Somewhere on the scale of influence lie financial motives: The investigator who conducts research on the efficacy of a treatment or diagnostic test but who also has a large financial stake in the company developing the products, or the investigator who conducts a clinical trial for a drug company from which he or she receives research money, consultation fees, and lecture honoraria. Not surprisingly, there are data that indicate that such relationships have the potential to exert influence—for example, a study examining authors' published positions on the safety of calcium-channel antagonists found that researchers who supported the use of these agents were more likely than those who did not to have financial relationships with the companies that sell them.1 Yes, the financial motive may well influence what researchers report. But it is only one among many motives, it is hardly the most powerful, and in cold cash terms it is small change. As a recent editorial in The Economist points out, “Science has always had to cope with conflicts of interest. The most awkward one a researcher can face is his own interest in the correctness of his hypotheses.”2 Nonetheless it's the financial conflict that gets the media ballyhooing and journal editors and bioethicists wringing their hands. Why the exclusive attention to just one of the many considerations that influence scientific research? An obvious answer is that financial dealings are often a matter of public record and thus easier to detect and verify. But money is not the only external and verifiable source of influence. The hypotheses stated in an investigator's grant, the date a grant comes up for renewal, an investigator's publication record, and the date when the person comes up for promotion also create a desire for particular research results and can be matters of public record. Do financial conflicts of interest present a greater hazard to public health than other conflicts? Clearly financial conflicts are most likely to be at play when research involves a potentially marketable product. And when financial considerations result in research that makes a product appear more effective, less toxic, or more reliable, the public suffers. Drug companies do strive mightily to design, analyze, and report research studies in a way that puts their products in the best possible light. Such sponsored studies often smack more of advertising than of science, and they need to be read as such. In an attempt to curtail some of the pharmaceutical industry's more troublesome actions, which in some recent highly publicized cases has included suppression of data and harassment of uncooperative investigators, the editors of prominent medical journals have collectively decided to refuse publication of drug-company sponsored studies “unless the researchers involved are guaranteed scientific independence.”3 The editors are right to do so. But the profit motive is not the only danger to public health. From bloodletting to routine tonsillectomy to the bland ulcer diet to psychoanalytic treatment of schizophrenia, medical history is replete with ineffective, sometimes dangerous, treatments, promoted primarily because their advocates believed in them and not because they stood to make money from them. We are hardly free today of research conducted by the advocate of a treatment who has little to gain financially from that treatment's acceptance but much to gain in recognition and esteem. Why are researchers called on to disclose their financial interests but not, say, their dates of grant renewal and promotion? And why do journal editors, bioethicists, and other guardians of scientific morality address, with suffocating sanctimony, the horrors of financial conflicts but leave untouched the more powerful, darker, and less governable motives that influence the research endeavor? Could the biases and motives of academia be at play? The folks who engage in financial-conflict hand-wringing are almost invariably full-time academics or well entrenched in the academic establishment. They are unlikely to be entrepreneurial and tend, like most academics, to be politically liberal and to have an intuitive distrust of business. Perhaps these individuals don't attend to the other motives influencing researchers because those motives are so pervasive and they have lived with them so long that they seem a normal and expected part of the research life. Possible “solutions” to the conflicts inherent in almost any study range from outright deception through data massage and statistical sleight of hand, to less than enthusiastic attempts to disprove one's hypothesis, to uncompromising truthfulness. But these dangers are at play regardless of the nature of the conflict. I like to think that most scientists are devoted to the truth and that when other considerations have an influence, the influence is inadvertent and operates outside the researcher's awareness. Inadvertent or not, how can we know when we read a research report that we are reading the truth? The answer is that we can't. The requirement that researchers disclose their relevant financial interests—widely recommended and, perhaps for good reason, widely ignored1,4—informs the reader only of the potential for a financial conflict. It doesn't tell the reader the only thing that's important: whether the researcher was swayed by those interests and whether the results are accordingly invalid. In addition, of course, financial disclosures don't tell us the extent to which the researcher was gripped by one of the more pervasive and powerful sources of bias. The scientific community has been sorting our the wheat from the chaff for a long time, far longer that it has been fretting over financial conflicts. The process can be laborious and time-consuming, but it works and there is probably no substitute for it. Fraudulent research, the history of science shows us, does have some distinguishing features. For example, in 1953 Irving Langmuir, a Nobel laureate in chemistry, gave a lecture on “the science of things that aren't so.”5 He discussed a series of “phenomena,” all of which had generated great interest and all of which proved to be nonexistent. The earmarks of this “pathological science” included: (1) the effect is of a magnitude close to the limit of detectability; (2) the theories put forth are fantastic and contrary to experience; (3) criticisms are met by ad hoc excuses thought up on the spur of the moment; and (4) only supporters observe the effects; critics can't reproduce them. The last is most important. The final, proper, and only trustworthy arbiters of research results are time and replication.