The new 14th edition of this reference book whose purpose ‘has from the start been to provide the health professional and medical investigator with a reliable and critical overview of all that is known – and much that is merely suspected but unproven – with respect to adverse drug reactions and interactions’ weighs more than 4 kg and is almost 2000 pages long. It contains 47 chapters with over 70 contributors. There are literally tens of thousands of publication references including 448 on contraceptive hormones alone. Most date back many years. It provides primarily qualitative information on the millions of reported adverse effects obtained from spontaneous, anecdotal case reports on the thousands of marketed drugs reported to agencies and journals. The value and substantial limitations of these reports are described in the Preface written by I. R. Edwards from the WHO Collaborating Center for International Drug Monitoring.
To this reviewer, this extensive volume may be of some value to health professionals as a reference, but will be less valuable to investigators since the discussion of formal epidemiologic studies is limited and generally uncritical. Indeed, it is surprising and disappointing that the principles and methods of such studies which have been extensive and ongoing for more than 40 years are given scant attention. When they are discussed in individual chapters for drug groups such as nonsteroidal anti-inflammatory drugs and contraceptive and noncontraceptive hormones, the presentations are incomplete and uncritical in terms of the quality of the research.
For example, the discussion of the important and somewhat controversial finding of an increased risk of idiopathic venous thromboembolism in users of third generation oral contraceptives containing gestodene and desogestrel compared with users of oral contraceptives containing levonorgestrel is summarized in one sentence. Only one of the original three papers on the subject published in the Lancet in 1995 and none of the additional studies is referenced. The next sentence states that ‘a fatal flaw of most studies is their failure to provide an adequate analysis of coexistent risk factors other than oral contraceptives.’ This statement is flatly wrong. All of the many properly conducted studies provide control for age, calendar time, smoking and body mass index.
The information of most direct value that this reference text provides relates to proposed drug interactions and pharmacodynamics. Most such studies are derived from well conducted experimental studies.
A volume of this kind should provide an informed and comprehensive review of the science of pharmacoepidemiology which has now provided quantitative evaluation of a large number of important adverse drug effects. Such studies are now increasing in number. As with spontaneous reports, some studies reach high scientific standards while others do not.