Randomised controlled trials 

Some trials comparing an intervention group with a control group are not randomised trials. Random allocation may be impossible, impractical, or unethical - for example, in a trial to compare the outcomes of childbirth at home and in hospital. More commonly, inexperienced investigators compare one group (such as patients on ward A) with another (such as patients on ward B). With such designs, it is far less likely that the two groups can reasonably be compared with one another on a statistical level. 

A randomised controlled trial should answer questions such as the following: 

		Is this drug better than placebo or a different drug for a particular disease?
		Is a leaflet better than verbal advice in helping patients make informed choices about the treatment options for a particular condition?

It should be remembered, however, that randomised trials have several disadvantages (see box) Remember, too, that the results of a trial may have limited applicability as a result of exclusion criteria (rules about who may not be entered into the study), inclusion bias (selection of subjects from a group unrepresentative of everyone with the condition), refusal of certain patient groups to give consent to be included in the trial, analysis of only predefined "objective" endpoints which may exclude important qualitative aspects of the intervention, and publication bias (the selective publication of positive results).

In a cohort study, two (or more) groups of people are selected on the basis of differences in their exposure to a particular agent (such as a vaccine, a drug, or an environmental toxin), and followed up to see how many in each group develop a particular disease or other outcome. The follow up period in cohort studies is generally measured in years (and sometimes in decades), since that is how long many diseases, especially cancer, take to develop. Note that randomised controlled trials are usually begun on patients (people who already have a disease), whereas most cohort studies are begun on subjects who may or may not develop disease. 

A special type of cohort study may also be used to determine the prognosis of a disease (what is likely to happen to someone who has it). A group of patients who have all been diagnosed as having an early stage of the disease or a positive result on a screening test is assembled (the inception cohort) and followed up on repeated occasions to see the incidence (new cases per year) and time course of different outcomes. 

The world's most famous cohort study, which won its two original authors a knighthood, was undertaken by Sir Austin Bradford Hill, Sir Richard Doll, and, latterly, Richard Peto. They followed up 40,000 British doctors divided into four cohorts (non-smokers, and light, moderate, and heavy smokers) using both all cause mortality (any death) and cause specific mortality (death from a particular disease) as outcome measures. Publication of their 10 year interim results in 1964, which showed a substantial excess in both lung cancer mortality and all cause mortality in smokers, with a "dose-response" relation (the more you smoke, the worse your chances of getting lung cancer), went a long way to showing that the link between smoking and ill health was causal rather than coincidental. The 20 year and 40 year results of this momentous study (which achieved an impressive 94% follow up of those recruited in 1951 and not known to have died) illustrate both the perils of smoking and the strength of evidence that can be obtained from a properly conducted cohort study.