Author response to “Clinical studies can be performed in an ethical manner”

Response to: Fleischmann R (2008) Clinical studies can be performed in an ethical manner. Nat Clin Pract Rheum 4: E5 doi 10.1038/ncprheum0856

Original article: Romain PL (2008) Access to clinical care via clinical trials: is it ethically possible? Nat Clin Pract Rheum 4: 166–167

In my Viewpoint article,¹ I asked whether it was ethically possible to provide access to clinical care via clinical trials. My answer remains a qualified “yes” and, although patient care and clinical research are different in many respects, I certainly agree with the comment by Dr Fleischmann that “clinical studies can be performed in an ethical manner”.² Despite there being many reasons for investigators to conduct clinical trials, including “prominence and financial rewards for clinical trialists”,³ I am not suggesting that investigators behave in an improper fashion just because they participate in such trials. The potential for an ethical problem derives from the misunderstanding that good clinical practice and good clinical trials have the same, rather than different and sometimes divergent, goals.

The distinct ethical requirements for individual patient care and for proper conduct of a well-constructed clinical trial (even with appropriate checks for patient safety), obligate the physician and clinical researcher, respectively, to different behaviors with respect to the patient, as discussed in my Viewpoint article.¹ For individual patient care, therapies have been tested to a sufficient degree to obtain approval for marketing, and the physician and patient both know what the treatment is. By comparison, trials are often conducted with double-blinding and placebo control. The benefit or safety of the experimental drug or approach are not defined to the same degree as an approved treatment, so the investigator is unable to provide information regarding benefits and risks with the same level of confidence in most cases. Failure to successfully communicate this to the trial subject creates a particular problem for both patient and physician.

Most importantly, it is common for patients in clinical trials to have inaccurate beliefs regarding the degree to which their care will be individualized, and even more common to have an unreasonable belief in the nature, or likelihood, of benefit.^1,3 The former problem (therapeutic misconception) is not thought to result from deliberate deception or the type of unethical behavior that Dr Fleischmann correctly asserts is not present in most trials conducted in the professional settings with which we are most familiar. As Sonia Shah has described, however, this may not always be the case in the developing world.⁴

Dr Fleischmann previously noted “It is the job of the investigator to fully explain to the patient all of the advantages and disadvantages of the study, as well as alternative therapies, so that the patient can make an informed decision as to whether to participate”.⁵ I would suggest that in doing so, it is especially important to emphasize to the patient the differences in approach to their treatment when they become a research subject, rather than purely a patient. The data suggest that this is not easy to accomplish, and improved strategies for doing so will enhance, rather than detract from, the ethics and important goals of clinical research.