Clinical Trials

❘❙❚■ Chapter 3 | Protocol DevelopmentIn double-blind studies, procedures on how to unblind must be stated. A separatesection with adverse event-related identification, reporting, and management ismandatory in drug trials.Practicalities of the trial in terms of assessments and periods (screening entry,treatment phase, patient visit numbers), blood and urine sampling, or otherinvestigations, measurements, or assessments are most appropriately given in atable format. In addition to study efficacy and safety variables, data quality-relatedissues should also be given in this section. Participant completion anddiscontinuation information, such as premature withdrawal of a participantfrom the trial, along with appropriate procedures for handling withdrawals,also constitute an important part. ICH-GCP requires that stopping rulesor discontinuation criteria, accountability procedures, randomization codesmaintenance, and breakage criteria, along with other details, should bespecifically mentioned in this section of the protocol.Trial designThe choice of trial design (eg, parallel-group trial, cross-over trial, factorial trial,cluster randomized trial) largely depends upon the research question that is beingasked. The design specification should be able to reflect the:• type of treatment and number of treatments• method of randomization• type of blinding• type of study question• study medicationFor example, in randomized clinical trials, while describing the study design, thetype of treatment (active or placebo) received by population groups should bedescribed, as well as the type of blinding (unblinded, single blinded, doubleblinded). A statement relating to superiority, inferiority, and noninferioritybetween the treatment groups should be given.Eligibility criteriaIn a clinical trial, the eligibility criteria aim to define the study population.The study population is a subset of the population with the medical condition inwhich the intervention is to be tested. Eligibility criteria are related to patients’safety and the anticipated intervention effect. The eligibility criteria will havea significant impact on the generalizability of the study results, as well as onrecruitment rates of the study; using eligibility criteria that are too restrictive canlead to difficulty in recruiting sufficient patients.30