The design of the trial

♦ It is often helpful to include a diagram ofthe design ofthe trial so that this can be seen at a glance. Fig. 7.1 shows an example of a summary design for a prostate cancer trial.

♦ List the eligibility criteria (see Section 4.2.3). These should define the type of cancer, the acceptable diagnostic evidence, the general characteristics of the patients, and should state the need for informed consent. Patients must be fit for either (or any) of the randomized interventions, and must not have previous or current illnesses likely to interfere with the protocol, the treatments, or the assessments ofthe outcome measures. Arbitrary restrictions that have no scientific basis, such as age limits, should be avoided. See also Sections 4.2.3 and 7.6.7.

♦ Describe the means of allocating patients to treatments, including, when appropriate, details of the randomization method (see Section 4.7).

♦ Describe the treatment policies to be evaluated and compared. Enough detail should be given for external referees to satisfy themselves that the interventions have the

Fig. 7.1 Example of a summary design for a prostate cancer trial

potential to be effective and are unlikely to be excessively toxic. Drug dosages should be stated and the number of cycles of chemotherapy and the intervals between them. Total doses and fields of radiotherapy should be stated and the number of fractions and the intervals between them. Surgical procedures should be given their standard name or, if necessary, described in detail in an appendix. How toxicity is to be graded should be indicated, and it may be necessary to describe how adverse effects are to be handled, particularly if novel approaches to managing them are to be part of the trial. Indicate which components of treatment are at the clinician's discretion.

♦ Indicate the frequency and duration of follow-up assessments. It is important to restrict the number of follow-up attendances to the minimum required for trial purposes. For example, it maybe necessary for patients to be seen monthly for satisfactory clinical management, but for trial data to be collected only every three or six months. It is good practice, in most cancer trials, to keep patients under follow-up until death, although for long-term survivors only minimal data may be needed. The frequency of follow-up must be the same in all treatment groups.

♦ List the outcome measures. The primary outcome measure is the one on which estimates of the size of the trial are made (see Section 5.2). It is often duration of survival. The primary outcome measure should be the most important outcome and one that can be unambiguously measured. Secondary outcome measures might include tumour response, adverse effects, disease progression, quality of life, and economic measures. All outcome measures should be justified as being necessary for answering the trial's hypothesis satisfactorily.

♦ Describe the data that need to be collected. Methods of recording adverse effects should be stated, including relevant laboratory tests; any quality of life instruments should be specified and referenced. Resist the temptation to collect data that are not needed for assessing the specified outcome measures.

♦ State the number of patients needed, indicating how this was calculated. In a randomized trial this involves estimating the likely outcome rates in the control group and the differences that are clinically worthwhile and can realistically be expected in the experimental groups. Give reasons for the choice of targeted difference to be detected. In equivalence trials, numbers are based upon the size of any differences that are to be excluded. Sample size estimation is fully discussed in Chapter 5.

♦ State the methods to be used in analysing the main outcome measures. Standard methods should be listed and, if necessary, referenced. State what, if any, subgroup analyses are planned.

♦ Indicate the expected frequency of confidential interim analyses for the data monitoring and ethics committee, although during the course of the trial the committee may decide that more or less frequent meetings are desirable.

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