Document 0188
 DOCN  M9590188
 TI    The ideal clinical trial: a clinician's perspective.
 DT    9509
 AU    Pinching AJ; Department of Immunology, Medical College of Saint
       Bartholomew's; Hospital, West Smithfield, London, UK.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:88 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291911
 AB    Therapy is always provisional, based on the patient's clinical state and
       on currently available evidence regarding potential interventions from
       clinical trial and other data. Acknowledging the continuing areas of
       uncertainty is important for patient choice in electing to initiate or
       continue a therapeutic intervention. However, recognition and acceptance
       of the limits of current knowledge also provide a crucial basis on which
       to pursue clinical trials to extend it. It is important to appreciate
       the intrinsic limitations of the clinical trial process in informing the
       particular circumstances of a patient engaging in a therapeutic
       decision. Trials, in order to meet their scientific objectives,
       necessarily impose certain constraints on eligibility, concomitant
       medication and end-points that may limit the generalisability of their
       conclusions. They have an element of caricature and tend to simplify the
       issues addressed because of the need to limit the variables in a patient
       population. They can be seen as having something akin to the
       relationship between opera and real life. In seeking an ideal clinical
       trial, the main objectives must be relevance, reality and robustness.
       Relevance needs to be to the actual questions of importance in the
       practicalities of patient care, conduct in the patient population to
       which the conclusions will be applied, and the likelihood of continuing
       relevance over the time frame of study. Realistic appraisal of the
       likely benefits of an intervention is essential and study design must be
       such as to ensure that there is maximum generalisability to the real
       life settings in which it is to be deployed. Robustness is a fundamental
       need to ensure that the outcome of the trial provides a secure basis for
       subsequent therapy, providing realistic appraisal of potential benefits
       and risks, in terms of clinically appropriate end-points and over a
       time-scale that is pertinent to the disease process. Phase I/II studies,
       apart from their role in evaluation of safety, are essentially
       hypothesis-generating and must be seen as such by all parties. They may
       need to be conducted in fairly pure populations to avoid confounding
       variables. It is usual to use surrogate markers for Phase I/II efficacy
       assessment, as a legitimate filter; however, they must be seen by all as
       being a prelude to large scale clinical trials (Phase III/IV) with
       clinical end-points, and not as providing answers in their own right.
       The definitive, hypothesis-testing clinical trials should be of
       sufficient size and duration to yield conclusions with clinical
       end-points, and with stopping rules based on clinical relevance, not
       just statisticsal significance. Trials should be flexible enough to
       relate as closely as possible to subsequent application and to enable
       the bulk of patient within the defined scope to participate. The
       conclusions of clinical trials must be published in a timely fashion and
       with clear delineation of what they do and do not show, and with a full
       and balanced account of benefits and hazards to allow patients and
       clinicians to make their own assessment of the applicability of the
       results.
 DE    *Attitude of Health Personnel  *Clinical Trials  Clinical Trials, Phase
       I  Clinical Trials, Phase II  Human  HIV Infections/*DRUG THERAPY
       *Patient Selection  Treatment Outcome  MEETING ABSTRACT

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