Clinical Trials

❘❙❚■ Chapter 7 | RandomizationWhy should patients in a clinical trial be randomized?The randomized controlled trial (RCT) is considered the gold standard for testingthe efficacy of medical treatments [1,2]. A fundamental assumption that formsthe basis of the RCT is that patients in different groups are similar for characteristicssuch as age, gender, social class, time of year of presentation, country of presentation,and type of hospital. In a large trial involving more than 1,000 patients, thesecharacteristics should be balanced across each group so that any difference seenbetween the groups at the end of the trial is then due to the different treatmentstrategies (ie, if patients do better in one group we can assume that this is due tothe treatment effect if not due to random error). This assumption is the basis ofall comparative statistical tests performed in the trial.To achieve this balance we randomly assign the patients (hence the termrandomized in an RCT) to each treatment strategy so that, for example, men havean equal chance of being given treatment A or B, people aged over 60 years havean equal chance of being given treatment A or B, and so on. Simple randomizationis one way of performing this balancing function, but other methods are neededwhen the number of patients is small.Minimizing biasA further requirement of randomization is that it must not be predictable by theperson assigning patients to the treatment strategies, otherwise there is a chancethat the groups will contain bias. To prevent this, certain methods of ‘blinding’ or‘masking’ are used so that patients and staff (with the usual exception of the dataand safety monitoring board) are not aware whether treatment A or B is the newtreatment, or even which group patients are in (active or placebo/standardtreatment), until the end of the trial. Physicians and study coordinators providingthe treatments to the patients use a randomization code to find out whichtreatment pack has been assigned to each patient (A or B), but the code providesno information about which treatment is which (active or placebo/standardtreatment). Randomization must be protected by blinding (see Chapter 8) so thatit remains unpredictable.How should the randomization code be determined?A randomization code is a list of which treatment a subject should receive.It is usually determined by a statistician using computer-generated randomnumbers or a random-number table. Some trials use methods for assigning66