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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biodegradable magnesium stents can achieve an immediate angiographic result similar to … other metal stents ….

      Nevertheless, the authors also commented in their Discussion:

      The absence of randomisation precludes direct comparison with other techniques of percutaneous revascularisation.

      Key features include the following:

       Design: No comparison group hence non‐randomised, multicentre,

       Size: 71 stents in 63 patients,

       Endpoint: Composite endpoint – MACE,

       Analysis: Proportion experiencing MACE with 95% confidence interval,

       Conclusion: Bioabsorbable stents can achieve an immediate angiographic result similar to other metal stents and can be safely degraded.

      The above examples of successfully completed clinical trials illustrate a wide range of topics investigated. These include patients with disease (breast cancer, colon cancer, eczema, glaucoma, malaria and diabetes mellitus), those requiring coronary artery stents or hand surgery, elderly residents of nursing homes, patients aged 25 years or more requiring at least two implant‐supported crowns for dental caries, healthy individuals and those requiring vaccinations. Although not included here, trials are conducted, for example, to evaluate different diagnostic procedures, different bed mattresses to reduce the incidence of bed sores, different dressings for wounds of all types and fertility regulation options for male and females of reproductive potential.

      These trials are often termed Phase III trials in contrast with Phase I and Phase II trials which are concerned with early stages of the (often pharmaceutical) development process. Although the trials differ in aspects of their design, the majority have the general structure of a two (or more) group parallel design in which eligible patients are assigned to receive the alternative options (often treatments but more generally termed interventions) and then at some later time assessed in a way which will be indicative of (successful) outcome. The outcomes measured in these trials include the following: survival time, gastric emptying time, reduction in disease activity, visual field status, recurrent parasitaemia, major adverse cardiac events, pain, the number of hip fractures, systolic blood pressure and standard criteria used to assess dental restorations. In the trial of homoeopathic arnica for pain relief following hand surgery, assessment was made in a double‐blind or double‐masked manner in which neither the patient nor the assessor was aware of the specific treatment option actually received.

      The methods used for the allocation to the options included simple randomisation of equal numbers per group, a 2 to 1 allocation; a minimisation procedure taking into account patient characteristics, randomisation to nursing homes (clusters) rather than to individual residents. For the split‐mouth design used for the comparing dental implants the authors’ state:

      For randomization of the implant type, a pregenerated random sequence was created … . Opaque envelopes were sealed according to pregenerated list. An independent judge prepared all envelopes. … an assistant indicated which implant had to be placed first following the indications contained in the sequentially number envelope.

      The non‐random allocation to a single‐arm study using a new bioabsorbable stent for coronary scaffolding might now be regarded as a feasibility study although the trial results were compared to that from historical data.

      The trials ranged in size from 20 patients with colonic cancer to 5102 women with HER2‐positive breast cancer. One trial involved 522 eyes from 271 subjects another 88 single implant‐supported crowns teeth in 34 partially edentate patients. Although not fully detailed in the above summaries, methods of statistical analysis ranged from a simple comparison of two proportions to relatively complex methods using techniques for survival time outcomes.

      1.3.1 Biological variability

      Measurements made on human subjects rarely give exactly the same results from one occasion to the next. Even in adults, our height varies a little during the course of the day. If one measures the blood sugar levels of an individual on one particular day and then again the following day, under exactly the same conditions, greater variation in this than that of height would be expected. Hence were such an individual to be assessed and then receive an intervention (perhaps to lower blood sugar levels) any lowering recorded at the next assessment cannot necessarily be ascribed to the intervention itself. The levels of inherent variability may be very high so that, perhaps in the circumstances where a subject has an illness, the oscillations in these may disguise, at least in the early stages of treatment, the beneficial effect of the treatment given to improve the condition.

      Example 1.13 Patient‐to‐patient variability – atopic eczema

      Source: Data from Meggitt, Gray and Reynolds (2006).

      With such variability, it follows that, in any comparison made in a biomedical context, differences between subjects or groups of subjects frequently occur. These differences may be due to real effects, random variation or both. It is the job of the experimenter to decide how this variation should be taken note of in the design of the ensuing trial. The purpose being that, once at the analysis stage, the variation can be partitioned suitably into that due to any real effect of the interventions on the difference between groups and that from the random or chance component.

      1.3.2 Randomisation