CLINICAL PHARMACOLOGY 2003 (PART 6)

We must be daring and search after Truth; even if we do not succeed in finding her, we shall at least come closer than we are at present (Galen AD 130-200)SYNOPSIS (CONTINUED) Surveillance studies and the reporting of spontaneous adverse reactions respectively determine the clinical profile of the drug and detect rare adverse events. Further trials to compare new medicines with existing medicines are also required.These form the basis of cost-effectiveness comparisons. Topics include: • Experimental therapeutics • Ethics of research • Rational introduction of a new drug • Need for statistics • Types of trial: design, size •...
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CLINICAL PHARMACOLOGY 2003 (PART 6) 4 Evaluation of drugs in manWe must be daring and search after Truth; even if we do SYNOPSIS (CONTINUED)not succeed in finding her, we shall at least come closer Surveillance studies and the reporting ofthan we are at present (Galen AD 130-200) spontaneous adverse reactions respectively determine the clinical profile of the drug and detect rare adverse events. Further trials toSYNOPSIS compare new medicines with existingThis chapter is about evidence-based drug medicines are also required.These form thetherapy. basis of cost-effectiveness comparisons. New drugs are gradually introduced by Topics include:clinical pharmacological studies in rising • Experimental therapeuticsnumbers of healthy and/or patient volunteers • Ethics of researchuntil enough information has been gained to • Rational introduction of a new drugjustify formal therapeutic studies. Each of these • Need for statisticsis usually a randomised controlled trial where a • Types of trial: design, sizeprecisely framed question is posed and • Meta-analysisanswered by treating equivalent groups of • Pharmacoepidemiologypatients in different ways. The key to the ethics of such studies isinformed consent from patients, efficientscientific design and review by an independentresearch ethics committee.The keyinterpretative factors in the analysis of trial Experimentalresults are calculations of confidence intervals therapeuticsand statistical significance.The potential clinicalsignificance needs to be considered within the As the number of potential medicines producedconfines of controlled clinical trials.This is best increases, the problem of whom to test them onexpressed by stating not only the percentage grows. There are two main groups: healthy volun-differences, but also the absolute difference or its teers and volunteer patients (plus, rarely, nonvolun-reciprocal, the number of patients who have to teer patients). Studies in healthy normal volunteersbe treated to obtain one desired outcome.The can help to determine the safety, tolerability,outcome might include both efficacy and safety. pharmacokinetics and for some drugs, e.g. anti- coagulants and anaesthetic agents, their dynamic 51 4 E V A L U A T I O N OF DRUGS IN MANeffect. For most drugs the dynamic effect and hence Therefore we provide a brief discussion of sometherapeutic potential can be investigated only in relevant ethical aspects (and particularly of thepatients, e.g. drugs for parkinsonism and anti- randomised controlled trial).microbials. These two groups of subjects for drugtesting are complementary, not mutually exclusive RESEARCH3 INVOLVING HUMANin drug development. Introduction of novel agents SUBJECTSinto both groups poses ethical and scientific problems(see below). A distinction may be made between: There are four main reasons why doctors should • Therapeutic: that which may actually have ahave a grounding in the knowledge and application therapeutic effect or provide information thatof the principles of experimental therapeutics: can be used to help the participating subjects and1. The optimal selection of a specific dose of a drug • Nontherapeutic: that which provides for a specific patient should be based on good information that cannot be of direct use to them, clinical research. To some extent, every new e.g. healthy volunteers always and patients administration to a patient is an exercise in sometimes. experimental therapeutics. ...