Parallel group studies/designs/trials

Other important issues are to do with the basic structure of trials. For example, what are the appropriate comparator treatments How many should be studied simultaneously Will the object of the trial be to find differences or to demonstrate equivalence Should a parallel group study or a cross-over trial be used How many centres should be used What should the block size be If a cross-over trial is employed will it be necessary to use incomplete blocks (These are designs in which each patient receives only a subset of the treatments being studied.) How long should the treatments be applied When should values be measured How should they be combined Should the results be analysed sequentially If the trial is to be blinded, how should this be achieved Is stratification desired What factors should be included in the analysis What is the general approach to be adopted What is the strategy for dealing with multiplicity of outcomes ... 

Finally, trials can follow parallel or crossover study designs. In a parallel trial, patients are assigned to a therapy that they remain on, and they are compared with patients in alternate therapy groups. In a crossover trial, patients switch or change therapy assignments during the course of the trial. 

The parallel-group, double-blind, placebo-controlled study design represents the golden standard of acute treatment trials of depression, mania and anxiety disorders. This design is intended to limit bias, in particular selection and measurement bias. Trials based on this design are expected to provide information about the effect size of a new compound and its side-effect profile. 

Many experiments could be carried out either as paired or unpaired studies. For example the rifampicin/theophylline experiment (Table 6.1) was performed on an unpaired basis -15 people received one treatment and a separate group of 15 received the other. This is referred to as a parallel groups trial. We could have used a paired structure, with 15 subjects receiving one treatment on one occasion and the other treatment at some other time (a cross over trial). The paired alternative would almost certainly have been a lot more powerful. However, it does not follow automatically that we should always be looking for a paired experimental design. The following points need to be born in mind ... 

Controlled trials can be conducted under matched pairs, parallel, crossover, group comparisons, or mixed design conditions. Parallel and crossover study designs each have advantages and disadvantages. Both can be used to compare two or more treatments, one of which may be placebo. In a crossover study, all treatments to be compared are administered to every enrolled patient in a carefully designed and blinded sequence with an interim drug washout period. Each patient receives all treatments and thus serves as his or her own control. 

The precise use of the placebo will depend on the study design, e.g. whether crossover, when all patients receive placebo at some point in the trial, or parallel group, when only one cohort receives placebo. Generally, patients easily understand the concept of distinguishing between the imagined effects of treatment and those due to a direct action on the body. Provided research subjects are properly informed and freely give consent, they are not the subject of deception in any ethical sense but a patient... 

The TQT study is a randomized, placebo- and positive-controlled clinical trial that can adopt a crossover design or a parallel-group design. The traditional four treatment arms are as follows ... 

As noted earlier, in the only double-blind, placebo-controlled, parallel design study of clonidine, Janicak et al. ( 264) studied a group of acutely ill, hospitalized manic patients, many with associated psychotic features. After a washout period averaging 1 week, patients were randomly assigned to receive either clonidine or placebo for a 2-week trial. The intent was to ascertain whether clonidine alone had any inherent antimanic properties, and therefore, no other concomitant psychotropics were allowed. Unfortunately, improvement in either group was minimal and did not differ, with some patients on clonidine developing problems with rash and hypotension. Doses of clonidine were comparable with those reported in prior positive studies, averaging 0.5 mg/day. 

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