Randomised Clinical Trials. David Machin

a Section 6 of the protocol named the eight participating centres.

      3.8.2 Implementation

      Whatever the design features of the randomisation process the protocol also has to address the method by which this is put into operation. This may range from a relatively unsophisticated telephone call or interchange of fax messages, to a web or even a voice‐based response system. Thus, the SQOLP01 (1999) protocol used a telephone‐based randomisation system the details of which we give below while a more recent EXPEL (2016) trial described by Kim, Chen, Tay, et al. (2017) opts for a web‐based.

      Example 3.15 Protocol SQOLP01 (1999, Section 7): Comparison of steroid with cyclosporine for the topical treatment of oral lichen planus

      7. Randomisation

      After the potential OLP case has been confirmed according to the eligibility criteria and informed consent has been obtained, the patient should be randomised.

      Some brief details will be collected for identification purposes and the caller will be informed of the result of randomisation and at the same time the patient will be assigned a protocol Trial Number.

      Example 3.16 Protocol EXPEL (2016): Peritoneal lavage after curative gastrectomy

      Enrolment and randomisation

      Having obtained informed written consent, potential subjects will then undergo surgery. If the patients are confirmed to have cT3 or cT4 disease and are amendable to radical gastrectomy with curative intent, they will be formally enrolled into the study and undergo randomisation. Study participants will be randomised to EIPL arm or standard arm based on random permuted blocks with varying block size of four and six, assuming equal allocation between treatment arms. The randomisation is stratified according to individual study site. A web‐based randomisation programme (https://rand.scri.edu.sg/) will be utilised to facilitate randomisation. The treatment code will be disclosed to the surgeon only at the end of gastrectomy. EIPL or standard lavage will then be performed according to the treatment code. The abdomen will then be closed as per standard.

      The method of obtaining the randomisation that is chosen will depend on circumstances but the trend is now towards more automated systems. However, this trend does not preclude simpler – yet reliable approaches that are likely to be more viable for trials of modest size. The SQCP01 (2006) protocol for management of clefts of the secondary palate in infants provided for both a telephone‐ and a web‐based randomisation option.

      The use of sealed envelopes by the clinical teams, as opposed to contacting a trials office remotely, is not regarded as an optimal method of allocation and should be avoided if at all possible. Whenever employed a clear justification for this is required. In the case of the investigators concerned with SQGL02 (1999) the nature of AACG, with its sudden onset and devastating consequences, provides the rationale.

      Example 3.17 Protocol SQGL02 (1999): Brimonidine as a neuroprotective agent in acute angle‐closure glaucoma (AACG)

       Procedure for randomisation

      Due to the acute condition of AACG, sealed envelopes will be used for randomising the patients who will be more likely to be presented to the clinician after office hours.

3.9 Assessment and data collection

      3.9.1 Assessments

      At some place in the protocol, an overview of the critical stages in patient management and key points of assessment needs to be provided. At each of these assessments, whether at the first presentation of the consenting individual before randomisation, post‐randomisation at visits when active treatment will be given, or for visits merely for check‐up purposes, the precise details of what examinations should be made and the details to be recorded (on the trial data forms) must be indicated. In SQCP01 (2006) even those children with cleft palate randomised to delayed surgery will have the same assessment schedule as those randomised to immediate surgery as these time points represent important milestones in, for example, their speech development.

      Example 3.18 Protocol SQCP01 (2006): Comparing speech and growth outcomes between two different techniques and two different timings of surgery in the management of clefts of the secondary palate

      Method

      Infants will be recruited at age less than 12 months and followed up until 17 years of age. They will be assessed at age 18 months, 3, 5, 7, 9, 15 and 17 years.

The PRESSURE (2000) trial lists the sequences of assessments under different headings, and for each provides details of precisely what is required. We have indicated these headings in Example 3.19 but only for their section 8.2.3 have we specified the details. The number of assessments depends on whether or not the patient has, or subsequently develops, pressure sores and also on how long they remain in the hospital ward. As one would expect, this contrasts markedly with SQCP01 (2006) which stipulates seven assessment times scheduled at various growth and speech development stages of the children.

Example 3.19 Protocol PRESSURE (2000): Pressure‐relieving support surfaces: a randomised evaluation

       8. ASSESSMENTS AND DATA COLLECTION

       8.1 Registration and randomisation

       8.2 Post randomisation assessments

       8.2.1 Immediate

       8.2.2 Daily

       8.2.3 Twice weekly up to 30 days and then weekly up to 60 days

      The research nurse or designated ward nurse will record the following