Читать книгу Randomised Clinical Trials - David Machin - Страница 137

Although great care should be taken in preparing the trial protocol, once the approved trial has opened for patient recruitment and is in progress, unforeseen circumstances may arise that impact on what is contained within the protocol. Such circumstances could range from the relatively trivial to the very serious. At one extreme, perhaps the packaging of a study drug is changed by the supplying pharmaceutical company without change to the potency or any significant aspects. At the opposite extreme, perhaps unanticipated and serious reactions in some patients occur, raising concerns about whether the trial medication is safe and consequently impacting on whether or not the trial should continue as originally planned. The consequences of the latter might for example either result in restricting the trial entry criteria by identifying those who are likely to be vulnerable and making them no longer eligible, or reducing the dose should the anticipated reaction occur. Both of these represent an important change to the protocol. The protocol would then have to go through a reapproval process. In contrast, the minor change in packaging may only require informing the authorities of this fact. Of course, in this instance, if the protocol has to be changed for any other minor reason(s), then it would be prudent to make this change(s) at the same time.

Figure 3.3 Consent form designed to obtain assent from a patient to be randomised in the multicentre COMPLIANCE (2015) trial in patients with breast cancer.

Source: COMPLIANCE (2015).

Since protocol modifications are not infrequent, it is wise to keep the protocol as concise as possible; exclude all irrelevant detail; ensure main sections start on new pages; ensure page breaks do not break paragraphs (perhaps not important in the Background but may be critical if describing details of an intervention); number sections, tables and figures in such a way as to minimise the need for future renumbering or repagination of the protocol. Without such precautions, there can be severe consequences if any additions or modifications happen to occur in sections from the early pages of the protocol.