Membership and functions of the trial steering committee
The membership and functions of the trial steering committee are summarized in Box 8.7. Their role is to provide an element ofindependent supervision over the conduct of a trial and, in this sense, fulfill an executive role for the sponsor. They are thus responsible for ensuring that the trial management group is fulfilling all its roles satisfactorily, and that any problems are dealt with rapidly and appropriately. The membership of the committee must enable it to have available all...
Unit of randomization individuals or groups
All the discussions above have assumed that an individual patient will be the unit of randomization, and for most cancer treatment trials this is certainly the most appropriate approach. In other settings, particularly primary care and hence in cancer screening and prevention trials, an alternative design has sometimes been used in which, rather than randomizing individual patients, groups of clearly defined patients are randomized. For example, one might randomize primary care practices, such...
References 1
1 Stephens, R., and Gibson, D. 1993 The impact of clinical trials on the treatment of lung cancer. Clinical Oncology, 5, 211-19. 2 Lara, P., Higdon, R., Lim, N., Kwan, K., Tanaka, M., Lau, D. et al. 2001 Prospective evaluation of cancer clinical trial accrual patterns Identifying potential barriers to enrollment. Journal of Clinical Oncology, 19, 1728-33. 3 Taylor, K.M., Feldstein, M.L., Skeel, R.T., Pandya, K.J., Ng, P., and Carbone, P. 1994 Fundamental dilemmas of the randomised clinical...
Introduction
With the best of intentions, medical interventions have the capacity to do harm as well as good, and before any new treatment is accepted into clinical practice it should pass through a series of pre-clinical and clinical evaluations to ensure that it is both safe and has some efficacy. Safety is usually first evaluated in laboratory studies followed by observations of either healthy volunteers or patients. Clinical effectiveness must be evaluated through some kinds of comparisons against no...
Barriers to taking part in trials
Although many patients are eligible to enter trials of cancer therapy, accrual rates are low and it is estimated that on average around 5 per cent of UK patients 1 and 3 per cent of US patients 2 take part. Trials generally rely on a minority of clinicians who have a particular interest in research and who recruit the majority of patients. However, even among highly committed doctors, accrual rates can be low. For example, a survey of members of the research-oriented US Eastern Cooperative...
Crossover trials
A further design which can require fewer patients than the corresponding parallel group design is known as the cross-over trial. Here, every patient receives all the treatments under investigation which may include a placebo , but the order in which they receive them is randomized. The general, simplified, design of a cross-over trial is shown in Fig. 4.6. In the case of a two-treatment cross-over trial, eligible patients are randomized to receive either A followed by B or B followed by A. An...
Alternative randomization procedures
Zelen's central thesis 10 was that patients receiving exactly the same treatment within a trial that they would have received outside of a trial did not necessarily need to be aware that they were in a trial. He therefore proposed what became known as Zelen's single consent design, which is illustrated in Fig. 4.2. In this design, patients who are eligible for the trial, and fit to receive any of the treatments which maybe allocated, are randomized without their consent. Those patients Fig. 4.1...
Phase IV Postmarketing surveillance
A new treatment may become established with relatively little knowledge of its long-term effects. 'Phase IV' evaluation usually refers to the study of adverse events and late morbidity and mortality in cohorts of patients who have undergone such treatment. These studies perhaps assume most importance when treating non-fatal conditions, where adverse effects may be relatively rare and or may not become obvious until some time after the efficacy of the treatment has been determined. Many phase...
Explaining randomization and rationale for trials
A major obstacle to trial participation appears to be explaining the randomization process. Some doctors may find it difficult or awkward to discuss, and participants may find the concept difficult to deal with. One study reported that 63 per cent of patients approached refused entry to a trial because of an aversion to randomization 25 , and it is thought that many trial participants do not fully understand the nature of the trials in which they are involved 9 . Other studies, which have paid...