Case reports: Someone writes up an interesting case they’ve seen. Case reports are good for generating hypotheses, but they don’t test them. Case reports rarely describe treatment failures. They only describe one patient (ie, “N=1”), so case reports almost never provide a basis for altering clinical practice.
Case series: Someone writes up a small number of similar cases. Case series have no control group and don’t test hypotheses, and they suffer the same susceptibility to bias as case reports. However, they reveal patterns among similar patients, and may lead to new hypotheses or suggestions for managing unusual or refractory conditions.
Case-control studies: Researchers select cases with versus without a particular outcome, and then ask subjects about prior exposures. For example, people with or without a current diagnosis of schizophrenia may be asked about exposure to cannabis. Case-control studies are susceptible to recall bias. They give an estimate of risk called the odds ratio.
Cohort studies: Groups of people are followed prospectively to see how many either with or without a particular exposure develop an outcome of interest. For example, people who do and don’t smoke cannabis are followed up after 10 years to see how many in each group developed schizophrenia. Cohort studies allow calculation of relative risk, but they are prone to misclassification and susceptibility bias.
Randomized controlled trials: Subjects are carefully selected and then randomized to treatment or placebo groups. RCTs evaluate the efficacy of treatment in the short-term, but they are costly to conduct. Some RCTs are “open-label,” meaning that subjects and researchers know what’s being given, while in “double-blind” trials no one knows who’s receiving treatment, and who’s receiving a placebo. Blinding can be difficult to accomplish, such as in studies where one treatment arm receives psychotherapy.
Systematic review: This is a review of research designed to answer a specific clinical question. For example, “what is the most effective approach for treating psychotic depression?” The Cochrane Collaborative (www.cochrane.org) produces many high-quality systematic reviews. Systematic reviews impose strict inclusion criteria on the studies they analyze, but publication bias poses a major problem.
Meta-analysis: Researchers use statistical methods to produce a weighted average of treatment effect sizes derived from multiple studies. The weight accorded to each study depends on sample size and quality. Some systematic reviews incorporate meta-analytic methods. Again, publication bias can strongly influence results.
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