Читать книгу Randomised Clinical Trials - David Machin - Страница 57

A crucial role of randomisation is to ensure that there are no systematic differences between the patient groups assigned to the different interventions. To preserve this situation, we need to, at all cost, avoid losing patients subsequent to randomisation, and we want to maximise the probability that the allocated treatment is indeed applied. Hence, it is extremely important to minimise the delays between consent, randomisation and the commencement of therapy.

In an ideal setting, once a patient has consented to take part in a clinical trial, randomisation should take place immediately. Once the treatment allocation is known, therapy should begin immediately following that. This minimises delay and avoids the patient having the opportunity to change his or her mind before therapy begins. This helps to prevent the dilution that can occur if a patient refuses the allocated treatment or switches to the comparator option in the period between randomisation and starting treatment. As we will discuss later, for purposes of analysis, such patients are retained in the treatment group to which they were allocated. Consequently, for example, a patient who switches from intervention A to B will still be retained in A for analysis, and this will make the effect of B appear more similar to that of A than might truly be the case. Thus, the prospect of dilution should be anticipated at the design stage and all steps taken to reduce this possibility to a minimum.

However, there will be many circumstances in which therapy cannot be initiated immediately. For example, in a trial comparing surgical options, there may be a delay until the surgery can take place because of the necessary preoperative workup procedures although trials have been conducted in which randomisation takes place, whilst the patient is on the operating table. In life‐threatening conditions, deaths may even occur before surgery can take place. For others, there is at least the possibility that their disease progresses in the intervening interval, and so, the patient is no longer operable. As with those who refuse or switch the treatments allocated, such patients remain in the trial analysis within their randomised group, and so, these too dilute the estimate of the real difference (if any) between the interventions to be compared.