Clinical studies can be performed in an ethical manner

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

Author's response: Romain PL (2008) Author response to “Clinical studies can be performed in an ethical manner”. Nat Clin Pract Rheum 4: E6 doi:10.1038/ncprheum0857

In a Viewpoint published in the April 2008 issue of Nature Clinical Practice Rheumatology, Dr Romain¹ discussed the ethics of physician-investigators conducting clinical trials. He provided several reasons for considering patients for trials, including provision of medication not otherwise available because it has not yet been approved by the appropriate agency(s), insurance or formulary restrictions, and lack of supply. Is the physician – investigator unethical if these are the prime reasons to conduct a clinical study in a practice environment? I do not think so.

Dr Romain suggested that physician-investigators conduct clinical trials for payment, authorship, protected time for clinical research, or for career advancement. In a non-academic clinical research center, where the vast majority of clinical research is conducted, the last two reasons cited by Dr Romain are invalid. Furthermore, most trials are now conducted with hundreds of investigators, and the chance that any one investigator will be listed as one of the four or five authors is remote. Although there is a potential for financial gain, most clinical sites do not have the financial expertise to accomplish this.² Dr Romain does not mention the primary reason for enrolling a patient in a clinical trial; that is the decision, based on extensive patient assessment, that the clinical trial affords the patient the best opportunity for safely obtaining clinical benefits.

It is the responsibility of the investigator to understand the investigators' brochure and to determine whether the tested product provides a reasonable risk:benefit ratio for each potential trial participant. The investigator must understand the potential benefit for the participant and the chance that the patient will achieve benefit. Moreover, the investigator must, by law, fully inform the participant before patient consent is requested. Information provided must include the potential risks and benefits, the likelihood the participant will have an adverse event, and the chance for benefit. Ethics committees have become stringent over the past few years with regard to not approving protocols that have an unfavorable risk:benefit ratio, do not provide the possibility of patient benefit, or do not provide a provision for participants who fail to respond.

If a patient does not experience reasonable efficacy at the time-point expected, the patient should be withdrawn. If the patient has an adverse event, and it is felt to be in the best interest of the participant, the participant should be withdrawn. If the physician-investigator is following Good Clinical Practice guidelines,³ then there is no conflict – patient safety comes first. The physician-investigator must follow the protocol and should select patients who are appropriate for the study and who have potential benefit – if in the course of the study there is no benefit or a safety risk develops, then the physician-investigator should, according to the Good Clinical Practice guidelines,³ become a treating physician and do what is best for the patient. This is not an ethical conflict, but is inherent to FDA regulations for conducting a clinical study. If a physician-investigator does not follow these regulations, there might well be FDA (government) sanctions.⁴

For these reasons, I feel that clinical studies can be performed in an ethical manner.