Of consents and CONSORTS: Reporting ethics, law, and human rights in RCTs involving monitored overdose of healthy volunteers pre and post the "consort" guidelines

Randomized controlled trials (RCTs) of therapeutic interventions in acute drug overdose present a significant challenge for ethical, legal, and human rights protections of research subjects, particularly when healthy volunteers are involved. The CONSORT statement on the uniform reporting of clinical trials was published in 1996 with the overall aim of improving the reporting of RCTs, both individually and to facilitate their inclusion into systematic reviews. In CONSORT, reporting of ethical, legal, and human rights protections, including prior evaluation of the study by an ethics committee and provision of informed consent, was largely an implicit requirement. Those drafting CONSORT may have assumed such protections and the rights of study subjects were secured by existing doctor-patient relationships. Alternatively, CONSORT may have been viewed as likely to indirectly enhance such protections, as a flow-on effect of improved RCT design and reporting. We wished to examine whether such assumptions were justified by examining the reporting of RCTs of simulated overdose in healthy volunteers. We reviewed all reported RCTs involving activated charcoal in healthy human volunteers for three years before the CONSORT statement (1989, 1990, and 1991) and three years afterwards (1999, 2000, 2001). Presence of documentation of inclusion and exclusion criteria, stopping rules, protocol deviations, information sheets, consent documentation, ethical approvals, conflicts of interest, understanding, refusal, inducements and coercion were recorded. We found a very poor level of reporting of some key ethical, legal, and human rights protections for healthy volunteers in toxicological RCTs. Reporting did not improve with the publication of CONSORT even in relation to requirements specifically included in the guidelines.