Case Reports. Single Case Reports can be useful in supporting intuitive reasoning, but as empirical evidence carry relatively little weight. The absence of case reports drawing attention to a given adverse reaction is particularly meaningless, as some may consider the relationship trivially obvious; or the publication of the observation could be blocked by the absence of supporting data.
Case Series. Case-Series are collections of case reports, or reviews of previously published case reports, which have one or more common features (e.g., drug exposure, type of adverse reaction). Some case series can provide essentially compelling evidence of a meaningful association, for instance, the otherwise extremely rare clear cell vaginal carcinoma found in woman fetally exposed to Diethylstilbestrol (DES Daughters). Nonetheless, as a rule, larger, more formal, and rigorous studies need to be performed to demonstrate association. Good case series depend on alert clinicians to identify trends either empirically or based on reasoning, leading to a new hypothesis.
Case Control Study. Individuals suffering an adverse reaction (e.g., lung cancer) are scored for various risk factors (e.g., tobacco smoking, vitamin A use) and age-, gender-, race-matched individuals are scored for the same risk factors. A higher rate of risk factors in one group suggests that such risk factors are in fact causes. A disadvantage of Case-Control Studies is that only Relative Risk and not Absolute Risk can be determined. Hazard Ratios, derived by Cox's polynomial method, is among the most elegant methods in Epidemiology.
Cross-Sectional Studies. Cross-Sectional or Prevalence Studies can be used to generate baseline data. A major problem when a statistically significant difference is found in a Clinical Trial (see below) or other well-designed experiment which the investigators then reject because one or both values conflicts with such baseline data. The comparison between a Cross-Sectional Study and another study is not valid since a different sample is used.
Cohort Study. As patient registries become more feasible in the informatics age, Cohort Studies are becoming more significant and useful as a means for performing epidemiological studies, both prospective and retrospective. A Cohort Study is simple in design, and involves the comparison of different experimental groups. Major advantages of Cohort Studies can include: detailed and accurate temporal information about exposure to risk factors and appearance of disease; study in a more naturalistic situation mimicking actual "market conditions" better than do clinical trials (e.g., no "recall bias"); multiple outcomes can be followed; both absolute risk and relative incidence can be determined; retrospective Case Control Studies can also be performed on the same data collected.
Randomized Double-Blind Placebo-Controlled Clinical Trials. A well-designed randomized double-blind placebo-controlled clinical trial can be an excellent experiment, performing a rigorous test with good sensitivity. Widely called the "Gold Standard", such Clinical Trials are unfortunately overrated above other epidemiological approaches by non-experts. A few of the weaknesses of Randomized Clinical Trials include: