Free How to Read a Paper: The Basics of Evidence-Based Medicine by Trisha Greenhalgh

(i.e. the selective publication of positive results, often but not always because the organisation that funded the research stands to gain or lose depending on the findings [9] [10]). Furthermore, RCTs can be well or badly managed [2], and, once published, their results are open to distortion by an over-enthusiastic scientific community or by a public eager for a new wonder drug [13]. While all these problems might also occur with other trial designs, they may be particularly pertinent when an RCT is being sold to you as, methodologically speaking, whiter than white.
Box 3.4 Disadvantages of the randomised controlled trial design
Expensive and time-consuming, hence, in practice,
     
many RCTs are either never carried out, are performed on too few patients or are undertaken for too short a period (see section ‘Were preliminary statistical questions addressed?’);
most RCTs are funded by large research bodies (university or government-sponsored) or drug companies, who ultimately dictate the research agenda;
surrogate endpoints may not reflect outcomes that are important to patients (see section ‘Surrogate endpoints’).
May introduce ‘hidden bias’, especially through
     
imperfect randomisation (see preceding text);
failure to randomise all eligible patients (clinician only offers participation in the trial to patients she/he considers will respond well to the intervention);
failure to blind assessors to randomisation status of patients (see section ‘Was assessment ‘blind’?’).
    There are, in addition, many situations in which RCTs are unnecessary, impractical or inappropriate:
    RCTs are unnecessary
     
when a clearly successful intervention for an otherwise fatal condition is discovered;
when a previous RCT or meta-analysis has given a definitive result (either positive or negative—see section ‘Probability and confidence’). Arguably, it is actually unethical to ask patients to be randomised to a clinical trial without first conducting a systematic literature review to see whether the trial needs to be carried out at all.
    RCTs are impractical
     
where it would be unethical to seek consent to randomise (see section ‘A note on ethical considerations’);
where the number of participants needed to demonstrate a significant difference between the groups is prohibitively high (see section ‘Were preliminary statistical questions addressed?’);
    RCTs are inappropriate
     
where the study is looking at the prognosis of a disease. For this analysis, the appropriate route to best evidence is a longitudinal survey of a properly assembled inception cohort (see section ‘Cross-sectional surveys’);
where the study is looking at the validity of a diagnostic or screening test. For this analysis, the appropriate route to best evidence is a cross-sectional survey of patients clinically suspected of harbouring the relevant disorder (see section ‘Cross-sectional surveys’ and Chapter 7);
where the study is looking at a ‘quality of care’ issue in which the criteria for ‘success’ have not yet been established. For example, an RCT comparing medical versus surgical methods of abortion might assess ‘success’ in terms of number of patients achieving complete evacuation, amount of bleeding and pain level. The patients, however, might decide that other aspects of the procedure are important, such as knowing in advance how long the procedure will take, not seeing or feeling the abortus come out, and so on. For this analysis, the appropriate route to best evidence is qualitative research methods (see Chapter 12).
    All these issues have been discussed in great depth by clinical epidemiologists, who remind us that to turn our noses up at the non-randomised trial may indicate scientific naiveté and not, as many people routinely assume, intellectual rigour [11]. You might also like to look up the emerging science of pragmatic RCTs—a methodology for taking account of practical, real-world challenges so that the