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

Автор: David Machin
Издательство: John Wiley & Sons Limited
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Жанр произведения: Медицина
Год издания: 0
isbn: 9781119524670
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treatment. This is the type of design used by Erbel, Di Mario, Bartunek, et al. (2007) to evaluate a bioabsorbable stent for coronary scaffolding. In such examples, the information for the Standard is retrospective in nature and is often obtained from clinical records only and so was not initially collected for trial purposes. If this is the case, the before‐and‐after design is likely to be further compromised as, for example, in the ‘before’ period, the patient selection criterion, clinical assessments and data recorded may not meet the standards required of the ‘after’ component. Such differences are likely to influence the before‐and‐after comparison in unforeseen and unknown ways.

      Example 1.14 Glioblastoma in the elderly – non‐randomised design

      Brandes, Vastola, Basso, et al. (2003) describe a study comparing radiotherapy alone (Group A), radiotherapy and the combination of procarbazine, lomustine and vincristine (Group B) and radiotherapy with temozolomide (Group C) in 79 elderly patients with glioblastoma. The authors’ state:

      The first group (Group A) was enrolled in the period from March 1993 to August 1995 … . The second group (Group B) was enrolled from September 1995 to September 1997 … . The third group (Group C) was enrolled from September 1997 to August 2000 and … .

      The authors conclude:

      Overall survival was better in Group C compared with Group A (14.9 months v 11.2 months, P = 0.002), but there was no statistical differences found between Groups A and B or between Groups B and C.

      However, since patients have not been randomised to groups, one cannot be sure that the differences (and lack of differences) truly reflect the relative efficacy of the three treatments concerned. This type of design should be avoided if at all possible.

       1.3.3.4 Case series

      A case series consists of a study in which the experience of an investigator treating a series of patients with a particular approach reports on their outcome. This may be the only ‘design’ option available in rare or unusual circumstances but is unlikely to provide clear evidence of efficacy. There are many criticisms of this design. Generally one may not know how the patients have been selected; the clinical team may have an eye for selecting those patients to be given the treatment who are likely to recover in any event: without further evidence of the natural history of the disease, we do not know whether the patients may have recovered spontaneously, without intervention: we do not know whether their approach to treatment is better than any alternatives.

      Control of the ‘experiment’ is clearly a desirable feature – perhaps easy to attain in the physics laboratory where experimental conditions are tightly controlled but not so easy with living material particularly if they are human. A good trial should answer the questions posed as efficiently as possible. In broad terms, this implies recruiting as few subjects as is reasonably possible for a reliable answer to be obtained.

      As we have indicated, the requirements for human studies are usually more stringent than in other research areas. For example, safety, in terms of the welfare of the experimental units involved, is of overriding concern in clinical trials, possibly of less relevance in animal studies and of no relevance to laboratory studies. In some sense, the laboratory provides, at least in theory, the greatest rigour in terms of the experimental design, and studies in human subjects should be designed (whenever possible) to be as close to these standards as possible. However, no consent procedures from the experimental units nor from animals, if they are involved, are required, whereas this is a very important consideration in all human experimentation even in a clinical trial with therapeutic intent.

Tabular representation of special considerations for clinical trials in human subjects

      Ethical considerations, as judged perhaps by a local, national or international committee, may also prevent the ‘optimal’ design being implemented. There are also issues related to patient data confidentiality which may, in the circumstances of a multicentre trial, make synthesis of all the trial data problematical. We address other components of Figure 1.3 in later sections of the book.

      As we have indicated, an important consideration at the design stage of a trial is to consider whether, if the new treatment proves effective, the trial will be reliable enough in itself to convince clinical teams not associated with the trial of the findings. Importantly, if a benefit is established will this be quickly adopted into national clinical practice? Experience has suggested that all too frequently trials have less impact than they deserve although it is recognised that results that are adopted in practice are likely to be from trials of an appropriate size, conducted by a respected group and have multicentre involvement. Thus, there are considerations, in some sense outside the strict confines of the design, which investigators should heed if their findings are to have the desired impact.

      Some basic or administrative things can help reassure the eventual readers of the reliability of the trial results. These include, although some of these may be mandatory, registering the trial itself, involving and informing other clinical colleagues outside the trial team of progress, careful documentation of any serious adverse events, ensuring the trial documentation is complete, establishing procedures for responding to external queries, clarity of the final reporting document in the research literature and seeking avenues for wider dissemination of the trial results.