Clinical Trials

❘❙❚■ Chapter 16 | Multicenter TrialsThe logistics of organizing a multicenter trialEthics approvalBefore a patient can be invited to take part in a trial, approval must be granted bythe participating institution’s ethics board. If such a board does not exist,independent ethics boards can be approached. Often, approval is also neededfrom the research and finance departments of each institution. Even beforeinstitutional approval is arranged, a national or regional ethics board might needto be approached for multicenter trials in some countries. Each country has itsown particular system, and it is the role of the coordinating team to discover andget to know the requirements and help local collaborators to work their waythrough the approval process.In the UK, for any trial conducted at five or more sites, an application must firstbe submitted for approval to a regional multicenter research ethics committee,and then to the relevant local research ethics committees covering eachcollaborating site. The documentation includes an approval application, theprotocol, the drug/device specifications, and any prior research information anddocumentation intended for potential trial participants.In the US, clinical trial protocols are submitted simultaneously to institutionalreview boards (IRBs) and the FDA, even before the centers are approached.The FDA submission is critical if data from the trial are to be later submitted tothe FDA for regulatory approval of a new therapy or device. The FDA hasa 30-day waiting period in which it can request further details of the protocol orask for amendments before the trial can begin at centers. The FDA may advise onany aspect of the protocol, but particularly on whether sufficient data will becaptured for later regulatory submission, such as toxicology and adverse eventdata, and the results of biochemical assays.Two broad types of IRB exist: those that are based within academic institutionsand those that are commercially operated. The former are responsible for ethicsapprovals for the hospitals within an academic network, while commercial IRBsmake their ethics assessments irrespective of which sites will be recruiting. Theapproval that commercial IRBs provide can subsequently be used by any numberof site management organizations (SMOs) without each SMO having to reapplyto their own IRB.IRBs and ethics boards are particularly interested in the safety and ethical aspectsof trials (eg, consent procedures and incentives used to recruit subjects). They mayrequest changes to consent documents, or changes in the trial design or protocol.This process can take several months, requiring further submissions and160