The Respective Roles of Controlled Clinical Trials and Cohort Monitoring Studies in the Pre- and Postmarketing Assessment of Drugs

Abstract

The respective roles of controlled clinical trials and observational studies (cohort or case-control studies) in evaluating the efficacy, safety and usefulness of a drug were analysed. A randomised, controlled, double-blind study is the best method of estimating the efficacy of a treatment. It provides the least biased and most robust estimate of the causal relationship. In certain situations and on the basis of certain criteria, observational studies can have a proof-of-efficacy value. Randomised, controlled, pre-and postmarketing authorisation (MA) clinical studies identify the rarer adverse effects and compare them with those resulting from the reference treatment. Before the MA, the pooled safety data from different controlled trials can provide an estimation of relatively frequent adverse events and subjects at risk. However, an observational study is the most appropriate method of evaluating the safety of a drug in the currently used conditions. By definition, a drug influences the health of a population if it directly or indirectly improves its health. A drug would have a major role in public health if it reduced mortality or morbidity related to a particular disease or if it improved the quality of life of patients with this disease. Prior to marketing a product, modelling is the approach of choice to quantify the expected effect. Pragmatic, postmarketing trials and observational studies are the reference methods used to define the population affected, the efficacy and safety of the drug in a real situation and its usefulness for public health. In conclusion, randomised clinical trials remain the reference approach for evaluating efficacy, while observational studies have a confirmatory value. Observational studies are the most appropriate way of evaluating safety in the currently used conditions, as the clinical trial has limited indications. In the interests of public health, modelling is the pre-marketing approach of choice, while pragmatic trials and observational studies are the postmarketing reference approaches.

Effect of dutasteride on the symptoms of benign prostatic hyperplasia, and patient quality of life and discomfort, in clinical practice

“…Indeed, randomized clinical trials also have limitations, e.g. restricted patient groups, and the value of proof‐of‐efficacy in clinical practice studies is widely recognized [10].…”

“…In these studies, dutasteride also had a favourable safety profile. While these clinical trials provide robust statistical evidence of the efficacy and safety of dutasteride in this setting, confirmation of the impact of dutasteride in real‐life clinical practice is warranted [10]. The extent to which results from clinical trials can be generalized to clinical practice can be limited by several factors, e.g.…”

Multicenter observational study of erlotinib therapy (OBSTAR) for non small-cell lung cancer: A GFPC study

“…Observational studies (cohorts and case-control studies) are the standard approach for evaluating the conditions of use of a new drug, for defining the target population, and for determining efficacy, tolerability and the public health benefit in real-life use [1,2]. Such studies show the real impact of a new drug and are complementary to randomised trials.…”

Études pharmaco-épidémiologiques : quels niveaux de preuve et comment les atteindre ?

“…[1] En 2004, la table ronde n°2 a débattu de la place relative des essais cliniques comparatifs et des suivis de cohortes dans l'évaluation pré et post-autorisation de mise sur le marché (AMM) des médicaments. [2] Les Ateliers de 2010 (table ronde n°5) ont abordé la place des études post-AMM sous l'angle de l'évaluation du risque et de la pharmacovigilance. [3] En 2011 enfin, l'étude de l'impact des médicaments en vie réelle a été analysée au travers des techniques de modélisation.…”