Randomised Clinical Trials. David Machin. Читать онлайн. Newlib. NEWLIB.NET

Автор: David Machin
Издательство: John Wiley & Sons Limited
Серия:
Жанр произведения: Медицина
Год издания: 0
isbn: 9781119524670
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are to be the participants, then a definition of ‘healthy’ is required. This definition may be relatively brief or very complex depending on the situation.

      At the early stages of the design process, one may have only a general idea of the types of subjects required although identifying the research question may have already made this reasonably clear. Thus, elderly patients may be the first target group for whom preventative action to reduce hip fractures may be considered. Then, when considering the trial question in detail, it might be decided to confine the elderly patient group to those residents in a nursing home. Further refinement may then, for example, define the elderly for trial purposes as those over 80 years of age and exclude those nursing homes who deal with psychiatric residents only. Considerations here might have been an anticipated very low fracture rate in those under 80 years of age and the difficulties associated with obtaining fully informed consent from patients with psychiatric illnesses. These selection criteria are easy to understand, easy to determine and therefore easy to apply in practice.

      In general terms, it is not advisable to restrict the patient pool for entry into a clinical trial as if too many restrictions are in place, the patient pool reduces accordingly so that the required number of patients for the trial takes longer to identify and so trial duration may become prolonged. Also, if those that are eligible comprise only a small subgroup of the total patient pool, for example, selecting only the moderate‐to‐severe cases from all those with atopic eczema, then the trial results will not have application to those with less severe disease. As a result, clinical teams are left wondering whether the trial findings are applicable to these patients. Of course, in this example extending the eligibility to less severe cases might not be sensible if useful treatments are already available for these patients.

      In determining eligibility, investigators should give as much thought as possible to ensuring generalisability of the subsequent trial results and therefore to define simple and minimal eligibility and exclusion criteria that allow the widest range of patients into the trial in whom benefit from the therapy may be anticipated. In many cases, these will include all the patient types for which the comparator in the trial is the current standard. If the eligibility criteria are too narrow then, however good the test treatment, the clinical implications will only be relevant to those small groups.

      In the context of trials in oncology, but equally applicable in all areas, Wright, Bouma, Dayes, et al. (2006, p. 844) warn:

      In a highly selected trial population, the question of generalizability becomes: how useful are the results of such a study in a more typical population of patients? Unfortunately such information is rarely reported, and oncologists and patients are left estimating how selected the trial population is and what implications it may have for applying the results of the trial in practice.

      A long list of eligibility criteria is also very time‐consuming to produce and to verify. Nevertheless, and despite the requirement for as few restrictions as possible on the entry requirements to a trial, patient safety is of paramount importance and every care must be taken to ensure vulnerable patients are not entered into a trial. Those that are vulnerable, in the sense intended here, are for example those who may be at high risk of a serious adverse event were they to take the trial medication or undergo the trial procedures. This is also often a major concern of the committees giving ethical approval for trials to be conducted.

      There must be specific reasons given for why a patient should not be included. For example, in some circumstances, pregnant women and those lactating (otherwise eligible) may be excluded for fear of impacting adversely on the foetus or the new‐born child.

      

      Example 2.2 Trial eligibility – partial thickness burns

      In a randomised trial by Ang, Lee, Gan, et al. (2001), patients with severe burns were emergency admissions into the specialist burns centre in Singapore requiring immediate treatment. Once admitted to the burns centre, only those patients with partial thickness thermal burns were eligible for the trial. Their consent was then sought and, once given, randomisation was accomplished by telephone to the statistical centre. Nevertheless, in certain cases, the attending medical team felt that the option of conventional therapy was more appropriate than the test therapy. For these patients, details of the clinical trial were not explained and conventional therapy commenced immediately.