4: Trial design

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4.1: Analysis, monitoring, and reporting
The main analyses that are expected to result from the trial should be developed in some detail, with the use of dummy tables. Such an exercise is a great help when planning the trial, as it helps clarify exactly what data are actually needed and highlights redundant data. All specific objectives should be tied to planned analyses.
4.2: The ‘SPIRIT’ checklist for standard protocol items for clinical trials
Nearly all intervention trials will need to have a protocol developed, which serves as the basis for trial planning, conduct, and reporting. Before a trial starts, it is recommended or, in many cases, required that the protocol is deposited in a trial register (see Chapter 7, Section 5). Until recently, there has not been specific guidance as to exactly what items should be included in such a protocol.
4.3: References
Arifeen, S. E., Hoque, D. M., Akter, T., et al. 2009. Effect of the Integrated Management of Childhood Illness strategy on childhood mortality and nutrition in a rural area in Bangladesh: a cluster randomised trial. Lancet, 374, 393–403.[Cross Ref][PubMed]
4.4: Introduction to trial design
Trials should be designed to produce unambiguous estimates of the effects of interventions, which are precise enough for public health planning. A common goal of all intervention studies, including trials, is to evaluate the effect of a specific intervention (or a specific package of interventions) applied in a specific manner to a well-defined population.
4.5: Definition of trial objectives
Once an idea for a trial has been formulated, it will be necessary to detail the specific objectives of the trial. To do this, the researcher will need to find out what has already been done regarding the evaluation of the intervention or interventions of a similar kind. This may involve meeting or corresponding with those undertaking similar studies, and it will almost invariably involve conducting a systematic literature review to find out what has been published that is relevant (see Chapter
4.6: Selection of interventions
Several criteria should guide the suitability of candidate interventions to be evaluated in a large-scale field trial. The intervention, or package of interventions, should usually be one that could be introduced into a national or regional disease control programme (though this criterion might not apply for ‘explanatory’ or ‘proof of principle’ trials—see Chapter 2, Section 3.3). The dose (when applicable) should be ‘optimal’. Evidence would usually be required from smaller preliminary studies
4.7: Allocation of interventions within the trial
Once a potential intervention has been shown to be safe and acceptable for use in humans and the dose schedule established, trials should be conducted to evaluate quantitatively the benefit attributable specifically to the intervention under trial, compared to some other intervention, while attempting to exclude the confounding effect of other variables. The best way to exclude the potential effects of other factors—both those already known to be confounders and also those that are confounders b
4.8: Choice of outcome measures and trial duration
For many interventions, there will be a range of outcomes that could be affected and which might be of interest to study (see also Chapter 12). Nutritional supplements, for example, might affect any or all of the following:
4.9: Trial population
The criteria for selection of the population to be included in the trial depends primarily upon what condition the intervention is directed against and upon the purpose of the trial. In general, the population will be chosen from an area in which there is high incidence of the condition of interest, because the higher the incidence of the primary trial outcome, the smaller the study population for the trial has to be. Exceptions are when the purpose of the trial is to determine the efficacy unde
4.10: Implementation
Critical to the conduct of a successful trial is that the trial population co-operates during the conduct of the trial and takes up the intervention offered. They must feel a part of the trial and perceive it to be for the benefit of their community. To ensure these aspects will require careful planning and investigation before the trial starts, including appropriate discussion with, and explanation to, community leaders and potential participants. Feedback and interaction should be continued th
4.11: Data handling
A necessary part of most trials will be the collection of baseline (pre-intervention) data. These will include identification information on participants, such as name, age, sex, place of residence, and information on other factors that may influence the risk of occurrence of the outcome measures under study in the trial.
4.12: Quality control
In most intervention studies, members of the population are invited to participate, the intervention is applied, perhaps repeatedly, and the population is kept under surveillance, until the final trial outcomes are recorded. The quality of each step in this process must be monitored.