“Abraham and Davis provide new insights into how the neo-liberal regime that has developed since the 1980s has profoundly biased the way the Food and Drug Administration and the European Medicines Agency deal with drug approvals and safety to the detriment of the patients they are supposed to be protecting. This book should be the starting point for anyone interested in understanding the forces that are shaping the medicines we take.”

Joel Lexchin, Professor of Health Policy, York University (Canada)

“Unhealthy Pharmaceutical Regulation explores the changes in the regulation of innovative pharmaceuticals in the neo-liberal period since 1980 covering the two regions that comprise the world’s largest medicines markets: the USA and the EU. This era witnessed the reduction in state intervention on business activity and the liberalisation of markets. In medicine, where evidence-based research is critical, empirical realists Abraham and Davis produce convincing evidence that the deregulatory changes were made in the commercial interests of the pharmaceutical industry, rather than public health. Eight years of research into the regulation of the pharmaceutical industry is brought together here in a single comprehensive resource. The authors successfully develop key theories with their empirical research, drawing widely upon interviews, and documentary and archival analysis. Pharmaceutical studies as an emerging field within the social sciences is marked by the 1995 publication of Abraham’s book Science, Politics and the Pharmaceutical Industry. This work applied theories from political sociology and political science to research in the pharmaceutical industry. In Unhealthy Pharmaceutical Regulation,  Abraham and Davis build on this work, exploring five theories key to understanding pharmaceutical regulation during the neoliberal period: Neoliberal Theory; Capture Theory; Corporate Bias Theory; Disease-Politics Theory; and Expectations/Marketing Theory. These are then brought to bear on case studies in later chapters. Abraham and Davis present a longitudinal macro- and meso-level analysis in the form of a political economy of the regulation of ‘innovative’ drugs during the neoliberal period, which offers the reader the context through which to later explore the case studies. The latter provides readers with a more micro-level perspective on a number of innovative pharmaceuticals in the context of key neoliberal deregulatory reforms, and within the framework of the theoretical perspectives referred to above. These allow the reader to explore to what extent those theories stack up against the evidence. The drugs and illnesses examined cover a number of therapeutic areas, from discussion of medicines developed to treat serious and life-threatening illnesses such as cancer, to others aimed at caring for non-life-threatening conditions, for example irritable bowel syndrome. Ultimately, all of these case studies demonstrate how the neoliberal corporate bias, which underpinned the deregulatory reforms, impacted upon the micro-social level of the decision making and regulatory outcomes of specific drugs, with detrimental effects on public health. This latest work from Abraham and Davis offers an extremely comprehensive discussion of the changes in drug regulation in Europe and the USA under neoliberalism. Through drawing on extensive fieldwork, they demonstrate how, in both these regions, the interests of the regulators and industry have become intertwined, with the former seeing the latter as partners or clients. Therefore, alterations in pharmaceutical regulation have been made in the commercial interests of companies, rather than those of patients and public health, with the result being that pharmaceutical innovations have not necessarily led to therapeutic advances. Abraham and Davis argue that when the interests of patients and the pharmaceutical industry do not coincide, it is the responsibility of regulatory agencies to ensure that they put patients first: ‘the lesson from the neo-liberal era is that regulatory standards need to be raised and extended in the interests of public health, rather than lowered and loosened’ (p.275). However, for this to happen, greater independence of the regulators from commercial influence is needed. Abraham and Davis end with practical suggestions of how this can be achieved. Most importantly, they argue that the industry and regulatory bodies need to be completely separated. This could be achieved, for example, through appointing agency heads that have a record of independence. Funding of the regulatory agencies should not come directly from the industry, but rather via the taxpayer, with governments recouping the costs from industry. Finally, they propose that scientists employed by the regulatory agencies, rather than the drug manufacturer, should conduct pre-market testing of innovative pharmaceuticals. In sum, Unhealthy Pharmaceutical Regulation is essential reading for all those interested in the field of pharmaceutical regulation, and it will be of great benefit to policy-makers, regulators, scholars, and students alike.”

Sociology

“Unhealthy Pharmaceutical Regulation is an impressive and important book. John Abraham and Courtney Davis focus on the reforms in pharmaceutical regulation in the United States and Europe in the period since 1995—reforms shaped by neoliberal political agendas. A key argument is that the reforms, though presented as in the interest of patients, have in fact been primarily in the interest of the pharmaceutical industry. The regulatory focus has shifted from ensuring safety and efficacy to speeding up drug approval, and while the latter is presented as benefiting patients by fostering innovation, the failure adequately to explore safety and efficacy prior to a medicine’s approval has had negative consequences for them.  The authors build up their argument in a careful, thorough manner, with detailed attention to a range of evidence. After a brief introduction discussing neoliberalism and the call for looser regulation, the first chapter delineates different social science approaches to pharmaceutical regulation and describes the authors’ theoretical and methodological approach. The research, carried out over eight years, includes interviews with regulators and scientists involved in drug approval processes along with extensive documentary research. Five theoretical approaches are described. The first, regulatory capture, focuses on the relationship between the regulatory agency, such as the U.S. Food and Drug Administration (FDA), and the industry, examining how the industry may actively seek to capture the regulatory agency or may do so more passively via the rotation of individuals from industry into agency and vice versa. The second, corporate bias theory, locates regulation in a broader political context of government policies responsive to industry interests, as with neoliberal policies from around 1980 onward. Here there is no need for direct capture of regulatory agencies, since corporate interests are placed at the forefront of the political agendas that shape the expectations and demands on regulatory bodies. The third, disease-politics theory, argues that the regulatory agencies responded to pressure from patient activists, particularly AIDS activists, who wanted easier and speedier access to new drugs. The fourth, reputational theory, a variant of disease-politics theory, argues that regulatory agencies seek to defend their reputations in the face of patient activism. The fifth, expectations theory, focuses on the role of industry marketing in generating patient and public expectations of technological innovation. The second, lengthy chapter examines the political economy of innovative drug regulation, mapping the regulatory reforms in Europe and the United States since 1995, the year when a centralized approval agency for Europe, the European Medicines Evaluation Agency (EMEA, now EMA), was established. One change was that EMEA and the FDA were increasingly funded from fees charged to pharmaceutical companies. Another was the introduction of “accelerated approval” by the FDA and “conditional marketing” by the EMEA. These categories were supposed to be restricted but in practice were used quite widely. Their introduction was presented as a response to patient activism, but while activism was used as a justification, the authors argue convincingly that it was not crucial. However, the speeding up of approval encouraged two significant developments. One was the willingness to rely on post approval evaluation to provide much of the salient information on safety and efficacy, even though in practice the agencies did not subsequently pressure pharmaceutical companies to carry out the appropriate trials they had promised. The other was an increased willingness to accept surrogate outcomes as adequate for drug evaluation, when frequently the links between the surrogate measures and the medicine’s impact on actual morbidity and mortality proved to be poorly related. A further feature of the new regulatory regimes was a tendency to conflate innovation with therapeutic advance—a new medicine might involve a mechanism with an innovative mode of action, but this innovation might not represent any therapeutic advance. Indeed, many innovative medicines did not. Chapters 3, 4, and 5 provide case studies of new medicines approved since 1995, all of which were eventually withdrawn by one of the regulatory agencies: medicines for diabetes, lung cancer, and irritable bowel syndrome respectively. These case studies show in considerable detail the factors underpinning the agencies’ decisions and the dangers to which they exposed patients because of the failure to obtain adequate information on side effects and adverse drug reactions prior to approval, as well as their tendency to regard the possible gains from the new medicine, such as greater consumer choice, as outweighing any identified side effects, even when the medicine did not represent any therapeutic advance. The case studies illuminate very effectively the operation of the agencies’ approval processes and how companies were typically given the benefit of the doubt. Chapter 6, the final substantive chapter, explores the way in which agencies sought to manage the increased risks associated with the regulatory reforms. Here the authors use several examples to demonstrate how the agencies typically chose to try to keep drugs on the market, even if they had toxic effects for some individuals: by trying to identify those who might be adversely affected (though often adverse effects were unpredictable), by restricting the pool of patients for whom a medicine was recommended, or by advising that it should be used only for a relatively short duration (even when the data showed that some were adversely affected after an even shorter period). In the conclusion the authors use the data they have collected to argue that while each theoretical approach has something to offer, that of neo-liberal corporate bias provides the best understanding of regulatory reforms since 1995—reforms that have served neither patients’ interests nor wider public health. This book should be required reading not only for those interested in health, medicines, and the pharmaceutical industry, but also for those interested in neoliberal politics and policies.” American Journal of Sociology

“This is a timely and important work. John Abraham’s study of a comprehensive school revives a neglected tradition of school case studies which is needed more at the present time than at any other since the 1960s. …. The effects of streaming in all its forms as a source of educational inequality need to be kept in the collective memory in order to counter ill-considered policy shifts of this kind. Divide and School provides a valuable service in this respect. …. John Abraham makes an important contribution to this debate. …. The study has an up-to-minute relevance and impact. Abraham has captured social processes that have become more widespread and intense …. [and] …. debated his findings in the context of today’s educational environment. Abraham takes a refreshingly new approach to gender differentiation …. and demonstrates that analysis of gender and class can complement each other rather than competing for space and emphasis. …. Abraham contributes real insight into the situated complexities of selection that are increasingly coming to characterize the more finely differentiated postmodern world in which we live. …. Abraham’s book should be treated as a serious contribution to the sociology of school selection. …. much of value will be gained from it”.

British Journal of Sociology of Education

“Brilliantly documents how the flawed drug industry/government axis allows Halcion and other dangerous, but real, nightmares to be approved and widely used. The book’s lessons, if learned and acted upon, can prevent further disasters of this kind occurring.” Public Citizen

“Provides a rigorous but accessible analysis of the story behind Halcion. It shows how the supposedly technical evaluation of the drug has in fact been captured by wider socio-political interests. John Abraham and Julie Sheppard make a compelling argument for greater transparency in drug regulation.”
Andrew Webster, Professor of Sociology of Science and Technology, University of York, UK

“A detailed and comprehensive book on a major drug debacle and an important contribution to the drug safety literature.”
Thomas J Moore, Professor of Health Policy, Georgetown University

“In Regulating Medicines in Europe, Abraham and Lewis rivetingly describe the effects of Europeanization on medicines control. The book is the result of five years’ research with dozens of interviews with regulators and members of industry and a meticulous search of the literature. In true Abraham style, it is rich with normally untraceable material, all fully referenced. The book also comes with an unmatched reference list. For completeness, comparisons are made between the UK, Sweden, and Germany. The arguments presented are forceful: the authors conclude that there is now much in current procedures that is undemocratic; that regulation of medicines is biased towards the interests of the pharmaceutical industry and trade over and above the interests of patients and public health; and that compromised safety arrangements are likely to be putting patients at risk. Regulating Medicines in Europe demands answers from regulators and deserves thanks from society. Here is a book that is likely to change thinking.”
British Medical Journal

“This book breaks new ground through interrogating European and global practices associated with the development of new drugs – the book deserves and demands a wide readership”
Professor Andrew Webster, Director of the UK Economic and Social Research Council’s Innovative Health Technologies Research Programme

“We are entering a period when a book like this will be immensely important – it provides a much needed new look at regulating medicines. Commendably calm and nicely structured, the book will also induce a strong stimulus to further research”
Graham Dukes, Emeritus Professor of Drug Policy Studies, University of Groningen

The evidence from this book is that the ostensibly progressive nature of geneticization has been conceptualized too narrowly. Moreover, this can be explained by understanding how it emerged and its subsequent integration into regulatory toxicology. Geneticization has undoubtedly produced new toxicological knowledge for scientists, but there is also the possibility that our societies will know less, rather than more, about the potential carcinogenicity of pharmaceuticals as a result of geneticization. This latter possibility raises the spectre of increased pharmaceutical risks to public health. Rather, like the film version of a book, geneticization has provided elaborate knowledge about those mechanisms identified for coverage, but the risk is that having seen the film people will no longer read the whole book, thereby missing important insights about the carcinogenicity of novel drugs, whose dangers reside in non-reductionist mechanisms. John Abraham shows that careful and sustained social scientific analysis can trace how specific political, institutional and commercial interests influence the development of regulatory science in particular directions that increase the risks to public health. This book helps to ensure that even in drug toxicology – the darkest corner of medicine – there can be an appreciation both of the technical significance of geneticization and the need to understand its bio-ethical, socio-political, and public health dimensions.

“John Abraham’s book on the relationship between the regulators and the pharmaceutical industry is a classic. Now, with the publication of Science, Politics and the Pharmaceutical Industry, Abraham has shown many of us up as amateurs. By systematically comparing licensing episodes relating to Opren, Feldene, Zomax, Naprosyn, and Suprol in the United States and in the United Kingdom, by taking advantage of the greater access to information in the USA, by scouring the literature and badgering the authorities, he shows convincingly that, when options present, regulators in both countries favour the industry. Moreover he demonstrates that such bias is as old as regulation itself. Much of the bias is the result of the industry’s lobbying skills, but there is also structural bias – if the bulk of government’s advisers are close to the industry their collective opinion will tend to favour the industry.”

British Medical Journal

“This book is a study of scientific research in the drug industry, and of its dissemination, publication and interpretation in the process leading to government approval of new pharmaceuticals. Abraham explores the selective acceptance of data that reflects the tendency of all involved to doubt results that threaten corporate interests. While focusing on the fine details of drug cases, John Abraham illuminates broader questions about truth, political power, and corporate science. The text is disciplined and meticulously documented and has explicit policy implications. Most compellingly, the author attends to the internal contradictions in the process he studies as a way to elucidate its ideological structure. This is the sort of book that demonstrates just how far we can take the methods of science studies and sociology of science. It draws on the excesses of epistemological chicken to present a realist analysis, and the end result is serious work that tries to understand a process that should be appreciated not only for its potential to play a role in improving drug regulation but also for its contributions to the respectability of our scholarly enterprise.”

Technology and Culture

“In the contested world of regulatory science, ‘bias’ is a contentious term to use. Abraham, in his book on the regulation of pharmaceuticals in the United Kingdom and in the United States, nevertheless uses the concept of ‘corporate bias’ contending that the commercial interests of the pharmaceutical industry have dominated both the construction of regulatory frameworks and regulatory decision making on specific drugs. Abraham rejects the view that drug regulation has evolved primarily to protect patient health interests spurred by drug disasters such as that of thalidomide. Instead, Abraham argues that a significant driving force for drug regulation has been to erect regulatory barriers to create privileged commercial opportunities for the larger drug companies, with the protection of consumers as a goal only at the margins. As a result, regulation has accorded undue weight to the importance of the commercial success of the pharmaceutical industry at the expense of ensuring therapeutic efficacy and safety. Such ‘corporate bias’ has been mediated through regulatory-scientific assessments. Abraham makes this case firstly from a detailed historical examination of policy in this sector. For example, the revelation in the 1970s of the Food and Drug Administration’s (FDA’s) clandestine ‘neutralization’ policy is cited as an explicit attempt to construct a regulatory culture sympathetic to industry by transferring ‘adversarial’ FDA scientists from regulatory assessment of particular drugs. Even in the supposedly transparent and adversarial world of FDA regulation, therefore, the frame of reference for regulation was actively structured to favor industry. In contrast, Abraham argues that in the United Kingdom, the opacity of the regulatory process has masked a permissive policy style of minimal regulatory action. This has resulted from a close relationship between regulators and industry in which the interests of the private and public sectors have become blurred by regulators’ reliance on industrial expertise and the revolving doors of employment between the two groups. To substantiate these claims, Abraham devotes five chapters of the book to the complex details of the regulation of five anti-arthritis drugs. Methodologically, to reconstruct and identify the ways in which corporate interests penetrate and become embedded in regulatory-scientific decision making, Abraham examines the role and character of scientific evidence in regulatory decisions. He examines patterns of systematic inconsistencies in the presentation, evaluation, and interpretation of scientific data on these drugs; scrutinizes the way that the benefit of the doubt has been awarded in technical conflicts and under situations of scientific uncertainty; and investigates how judgements are made about acceptable and unacceptable risk. The chosen cases illustrate the different ways in which regulators’ and industry’s actions, as well as the systems of regulation, may be interpreted as serving commercial interests. The case of the drug Opren is a vivid illustration of how manufacturers withheld evidence to influence the drug’s assessment; this represented a deviation from acceptable practice and resulted in consequent criminal prosecution. In the case of the drug Naprosyn, regulatory inaction pending retesting following the discovery that fraudulent data had been used to support its approval is taken to imply an implicit shift in the burden of proof in a direction that favoured industry. When the drug Zomax tested positive in a carcinogenicity trial, it was nevertheless approved because the regulatory issue became reformulated as one of risk toleration rather than risk avoidance. Using the resources provided by the U.S. Freedom of Information Act, Abraham is able to document in some detail the argument that the U.S. regulatory system, often characterized as transparent, adversarial, and rule based, can be loaded in favor of the commercial concerns of industry. In the absence of such a rich source of information in the United Kingdom, the criticism of its secretive, consensual, and discretion-based system is based on more general imputation. In the case of the drug Feldene, for example, Abraham argues that the opacity of the U.K. system permitted considerable institutional discretion in the closure of the dispute over its safety in a way that was excessively favourable to its manufacturers. In contrast, in the United States, where discretion is narrower, Feldene was approved because of the FDA’s adjustment of the threshold of significant risk. Similarly, Abraham describes how the FDA rewrote its statistical rules so that in the case of the drug Suprol, a significant carcinogenicity finding came to be represented as marginal and thus did not prevent the drug’s approval. At the analytical level, Abraham disputes what he sees as the conflation of ‘bias’ and the mere presence of values. In his view, this conflation underlies prominent cultural relativists’ claims that ‘all is bias’, that, in other words, each interest group simply follows its own impeccable logic. From a realist sociological position, Abraham considers that far from there being plural rationalities for the construction of regulatory-scientific arguments, there is a common rationality of agreed standards through which the plural bases for constructing those arguments can be critically examined. Therefore, for Abraham, the identification of overt lying, of deviation from set standards of scientific practice, or of the more subtle opportunistic interpretation of data in ways that converge with corporate goals is a means of disentangling the relationship between the rhetoric of safety assessment and the practice of regulatory scientific approval. …. The case studies suggest that whereas the commercial interests of the pharmaceutical industry may have pervaded regulatory scientific decisions, there is a constant interplay of interests between and within industry, government, and patients-concerning a drug’s commercial profitability, therapeutic efficacy, and safety. These interests may diverge and converge at different times and have differing influences on regulatory assessment. The import of the book and policy value is in explicitly revealing embedded social assumptions in regulatory scientific decision making and in examining the ways in which these can be changed to serve more explicitly the interests of patients in being given safe and efficacious drugs.”

Science, Technology & Human Values