Clinical Trials

❘❙❚■ Chapter 32 | Overview of Reportingmisinterpretation of the results whilst being tailored to the needs of the targetaudience – a task that requires great care.Interpreting a trial reportThere are two distinct forms of validity of a study: internal and external validity.Internal validity is defined as the ability of a trial to study the hypothesis ofinterest. External validity is the generalizability of the study findings, ie, the extentto which the results can be applied to clinical practice.Internal validityInternal validity is concerned with study design and conduct. The study design ischosen in such a way that biases and errors are minimized. These include systematicerrors, confounding, and random errors; in clinical trials, the randomization andselection procedures aim to ensure a lack of confounding and selection bias.Key factors are a randomization scheme with masking so that neither doctors norpatients are aware of the participants’ intended allocation, as well as blinding tothe treatment allocation during follow-up. False-negative and false-positivefindings due to random error can be avoided by choosing a sufficiently large studypopulation (see Chapter 9). Study size and statistical analyses should be chosenwith reference to the hypothesis of interest.External validityExternal validity is a function of the selection of the study population, treatmentregimens, and outcome measures. The study population should represent thepopulation that is intended to receive the treatment in the population at large,should there be a positive result. Treatment regimens should be practicable andrelevant to clinical practice. Outcome measures should reflect measures of clinicalinterest (ideally these should be hard outcomes, such as mortality or morbidity)or at least routine measurements that apply to clinical practice. Since diagnosticcriteria and treatment guidelines change over time, it is essential that thereader understands the context of the study with respect to current and pastclinical guidelines, and clinical practice.Sufficient informationAll of the above points should have been clarified during the planning of the trial.Large clinical studies often publish a study design paper early in the process,where the rationale, assumptions, and study design are laid out in detail. However,the interpretation of a trial report relies on the reader’s ability to identify potentiallimitations in the design and conduct of a trial. Therefore, any clinical report368