Problems with ethical approval, and how to fix them: lessons from three trials in rheumatoid arthritis

Internationally, clinical trials are subject to costly and onerous regulation which aims to ensure trials are well designed, with risks to participants minimised wherever possible, and any significant outstanding risks communicated clearly to participants. We set out to assess how well current regulatory frameworks meet these aims, and the extent to which the relevant regulatory documentation can be accessed for independent scrutiny. A recent study reported that over 10,000 Rheumatoid Arthritis (RA) patients have been randomised to control groups receiving ineffective treatments in trials of biologic disease-modifying antirheumatic drugs (bDMARDs), risking “irreversible deterioration in condition”. We investigated the process of ethics approval, and the information given to patients, for two trials of ocrelizumab included in this report. We also reviewed documents for one homeopathy trial on RA, as problems with ethics approval and informed consent in complementary and alternative medicine (CAM) have been reported. Below we describe the methods we used in attempting to obtain relevant documents, the barriers we faced, and the ethical shortcomings we identified. RA is a common disease for which many new therapies have been developed over the last 2 decades; it is therefore an exemplary setting for exploring these issues, which are relevant to clinical trials of interventions in all areas of medicine.