A case study evaluation of ethics review systems for multicentre clinical trials

Abstract

TO THE EDITOR: The evaluation by Hicks and colleagues of the centralised ethics review system in New South Wales codifies important additional time delays facing researchers conducting multicentre trials that include NSW. These delays have direct financial consequences that continue to limit the viability (especially when staff are on time-limited grants) and productivity of multisite research in Australia, without adding value to the ethical conduct of the research. There is also inconsistency between the approaches of the lead ethics committee (LEC) and site-specific ethics committees in the way they deal with protocol amendments and adverse event governance, further compounding the delays in initial review. Five multicentre clinical trials are currently being conducted by the Palliative Care Clinical Studies Collaborative (PaCCSC), a national initiative to improve the evidence for symptom therapeutics at the end of life. Submissions for ethics review occurred between May 2008 and July 2009 across nine sites in five states. As in the study by Hicks et al, ethics review submissions included the NSW LEC, but because these submissions were more recent than those reported by Hicks et al, they were submitted on the National Ethics Application Form (NEAF). Hicks and colleagues state there is benefit in standard documentation, but using the NEAF does not reduce the need for collating complete sets of documentation for each site-specific approval and any subsequent amendments or adverse events.4 For the PaCCSC, LEC and site-specific review in NSW achieved approval in a median of 119 days (range, 76–209), compared with 107 days (range, 6–172) for individual committees in other states. Hicks and colleagues did not quantify the costs generated by these delays. Given that staff are often employed to prepare ethics submissions and then retained for the definitive study, additional delays in approval are costly, especially with finite, competitive grants funding. Costs of multisite ethics review applications have previously been quantified in Australia, but the additional delays in NSW from the requirement for site-specific approval are estimated to have cost the PaCCSC about $4000 per study per site in salaries and on-costs. Across three NSW sites and five studies, $55 000 has been spent without measurable ethical or research governance benefits. Theoretically, LEC review should streamline protocol amendments and adverse events reporting, as they are the responsibility of the LEC. But although protocol amendments are supposed to be reviewed only by the LEC, some site-specific committees continue to insist on approving all amendments. Efforts to consolidate adverse event reporting have made some progress. All adverse events are reported to the LEC for review, and any required response should be shared with site-specific committees. Again, some non-lead sites continue to insist on separately reviewing adverse events rather than using the LEC as intended.