Serious Ethical Dilemma of Single-Agent Pegylated Liposomal Doxorubicin Employed As a Control Arm in Ovarian Cancer Chemotherapy Trials -- Markman JCO commentary

"...It is essential that those reading this letter do not misinterpret its meaning. There is absolutely no intent in this discussion to vilify any individual, organization, or company involved in the oncology drug development paradigm. It is unquestionably the case that all working in this arena have as their major goal the advancement of antineoplastic strategies that are effective, relatively safe, and that improve the survival and quality of life of patients with cancer.


But if the current rules, or their interpretation, result in research subjects being subjected to the potential to experience a truly unnecessary risk of serious harm, and this is done to satisfy regulatory requirements solely for the benefit of an unrelated third party (in this situation a pharmaceutical/biotech company), the situation must change.

And if it does not, it is appropriate to call on all local institutional review boards, whether in academic or community-based centers, and in the developed or developing world, to very seriously consider rejecting their site's participation in such a study unless the PLD dose is reduced.

For is that not the purpose of such reviews, to evaluate the relative and acceptable risks to patients who agree to participate in a clinical research study and to ensure individuals considering entering a trial are provided adequate informed consent? And in this specific setting it must be pointedly asked: how adequate can that consent possibly be if individuals are not provided clear and full disclosure of the documented efficacy as well as toxicity data associated with the 50 versus to 40 mg/m2 dose of PLD in the treatment of platinum-resistant ovarian cancer?

Finally, individual investigators who have agreed to enter patients into such a study should perhaps be directly asked what dose of PLD they would personally routinely prescribe for their patients with ovarian cancer who are not participating in this trial? If the truthful answer is 40 mg/m2 (or any dose < 50 mg/m2) what possible acceptable ethical justification can they provide for agreeing to treat patients on this trial at the higher, more toxic dose level?"