Focusing pharmaceutical research on patient care: Using clinical trials to develop clinical decision rules

This paper discusses implications for patient care and pharmacotherapeutic research of patient-care-centred approaches to clinical trial design and analysis. Evidence-based medicine regards the modern double-blind, placebo-controlled, clinical trial with randomised assignments of patients as the gold standard for drug development and patient care. These clinical trials use group comparisons to argue for the efficacy and tolerability of drugs or medical devices. In preparation for clinical trials, investigators practise to improve inter-rater agreement on outcome measures to reduce variance within treatment groups not to improve test-retest reliability with individuals. With attention to the test-retest reliability of clinical outcome measurements used with individual patients, investigators can track the clinical course of each individual patient in a clinical trial. Analysis of clinical trials for treatment efficacy in individual patients develops clinical decision rules. These clinical decision rules allow practitioners to base patient management decisions on clinical trial evidence rather than on unsystematic clinical judgements about a patient’s clinical status. Clinical trials extended tostudy treatment effects in individuals can scientifically ground practitioners’ clinical treatment decisions. Physicians and patients may be concerned that these extended clinical trials intrude inappropriately into the physician-patient relationship. These concerns are unwarranted. The new methods better implement clinical trial evidence in the treatment of disease; they facilitate, and do not interfere with, the physicianpatient relationship — the care of the person. Using test-retest reliability studies the extended clinical trial develops confidence intervals of measurement for outcome measures. These estimates of reliability allow outcome measures to be used as indicators of each patient’s true clinical course. This control over reliability allows investigators and practitioners to use clinical trial evidence to identify responding and non-responding patients, provides earlier detection of patients who initially respond but who then lose the response to treatment, and estimates the importance of the treatment for the patient’s recovery. Extended clinical trials should allow physicians to better manage patients, and patients to become better informed and more confident in their treatments. Extended clinical trials offer various opportunities to commercial developers of drugs. The extended clinical trial meets current United States Food and Drug Administration and other governments’ regulations for a new drug application because both traditional and individualised analyses can be carried out on the dataset. Drugs losing or without patent protection can be protected by a company’s proprietary patented methods of drug development, and expensive drugs can be justified for use in those individual patients where the drug demonstrates unique clinical advantages. The development and application of extended clinical trial methods depends on a number of factors: further research to confirm the integrity of the methods; physician and patient acceptance; pharmaceutical companies deciding to use extended clinical trial designs and analysis in drug development; or regulators requiring more clinically relevant clinical trials for drug approval.