Identificació de reaccions adverses greus a nous medicaments

Abstract

In the 1960’s, pharmacovigilance was mainly based on case reports. Since the 1980’s, observational studies helped to identify new adverse drug reactions which have a big impact on public health, and they have also quantified their risk. Since 2000, clinical trials and meta-analysis have also contributed significantly to the discovery and evaluation of the risk of relatively frequent adverse effects._x000D_ _x000D_ In the last 30 years, Butlletí Groc has reported on all the news regarding s adverse drug effects and their impact on public health, and through this magazine we can learn about the discoveries, concerns and controversies._x000D_ _x000D_ The aim of this study is to examine the evolution of methods, drugs and diseases of interest in pharmacovigilance looking at articles published in Butlletí Groc over a period of 23 years._x000D_ _x000D_ The articles published in Butlletí Groc from 1988 to 2011 were classified into five categories. Those related to toxicity were selected to analyze drugs and therapeutic groups involved (according to ATC) and adverse effects (according to MedDRA). Adverse reactions related to safety problems of a drug or group of drugs were classified according to the mechanism of action (type-A or type-B) and the method used to identify them. Of the drugs withdrawn from the market in Spain from 1982 to 2013 due to safety reasons, drugs and adverse reactions involved were also evaluated, as well as the type of reaction, the method identified, and time to market._x000D_ _x000D_ Among 244 articles published in Butlletí Groc between 1988 and 2011, 184 dealt with drug toxicity. Of the 116 selected, 132 were concerned with safety problems of a drug or group of drugs. The main groups of drugs involved were those active on the nervous system, cardiovascular, NSAIDs and others active on the musculoskeletal system, active drugs on the digestive system and metabolism, and systemic anti-infectives._x000D_ _x000D_ The main adverse reactions led to hepatobiliary, cardiovascular, psychiatric and neurological diseases. Half of the adverse reactions were described as type-A, and half type-B, but the diseases have changed over time, so there has been increasing interest in the effects of type-A, at the expense of type-B._x000D_ _x000D_ Meanwhile, the methods of identification and assessment of adverse reaction causal relationship with exposure to the drug have changed, so that observational studies, clinical trials and meta-analysis have partly replaced reporting and case series. The proportion of drugs with no intrinsic value or described as unacceptable has fallen since the 1990’s._x000D_ _x000D_ The analysis of the drugs withdrawn in Spain from 1982 to 2013 reveals that the main therapeutic groups involved were those active on the musculoskeletal, nervous, cardiovascular, and digestive systems. The main subgroups were NSAIDs, drugs for obesity, anti-depressants, and vasodilators._x000D_ _x000D_ During 30 years of observation, the time between the marketing and the withdrawal of a drug for safety reasons has lengthened rising, from 8 years between 1982 and 99 to double the length of time between 2000 and 2003. The most frequent adverse reactions were hepatic, cardiovascular, and neuropsychiatric. Hepatotoxicity has been the main cause of drug withdrawals during the whole study period, but since 2000 cardiovascular reactions are the most common causes._x000D_ The main reasons for concern have evolved from being worried about rare and severe adverse reactions type-B to worries in type-A, which are more frequent and have more impact on public health. The methods used in deciding to withdraw a drug have also evolved since the case series in the early years to using observational studies and meta-analysis of clinical trials, which are mainly used to detect problems and quantify risks.

Date of Award	22 Jan 2016
Original language	Undefined/Unknown
Awarding Institution	Vall d'Hebron University Hospital (HUVH)
Supervisor	Joan Ramon Laporte Rosello (Director)