Stephen H. Jenkins, How Science Works. Evaluating Evidence in Biology and Medicine, Oxford-N.York, Oxford University Press, 2004.

Statistical literacy is becoming an issue of growing concern for scientists and philosophers alike, the underlying drive being the social impact it has on a variety of realms. Sociologists (e.g. Beck) have made us aware of the relevance of risk assessment in our everyday life, while psychologists (e.g. Gigerenzer) revealed that our statistical estimations are usually biased, albeit for good evolutionary reasons. To trust in the statistical expertise of scientists might then seem a wise choice when their empirical findings are invoked to support such decisions as, say, the promotion of vitamin C for our health improvement or a conviction on the basis of DNA identification. The immediate question is to what extent this public trust is justified.

The improvement of our understanding of statistical evidence in biology and medicine is precisely the goal of How Science Works and the argumentative strategy of the biologist Stephen H. Jenkins could not have been more effective. Each of the nine chapters of his book provide an introductory presentation of the evidence available concerning an equal number of fascinating topics: besides the two mentioned above, Jenkins discusses environmental and ethological issues (such as the decline of certain amphibian populations or the cognitive mechanisms that control the storage of food in certain species), medical subjects (the causes of cancer and aging, the effects of coffee), or a combination of both (the influence of climate change on the spread of malaria). Intended as brief reports on the work in progress in all these areas, each one of them contributes to the making of a single methodological point: what the statistical analysis proves in these nine cases is that there are as yet no ultimate answers.

What Jenkins argues is that this inconclusiveness arises from the very complexity of biological and medical research, even after being tamed by the most sophisticated statistical techniques available. There are many sources of evidence and various possibilities to incorporate them into our theories. On the one hand, Jenkins presents a number of standard bio-statistical methods that allow us to design experiments and analyze data with various degrees of reliability. The art of the biomedical scientist would lie in the achievement of a certain consilience between all these sources, together with more traditional ones, such as fieldwork. Jenkins shows that this is not an easy task, as the evidence might prove unavoidably conflicting. Several philosophical dilemmas come to complicate even more data analysis. To name just three, let us think of the typical disjunction (sometimes inclusive, often exclusive) between case studies and all-encompassing theoretical approaches, the difficulties of accounting for the simultaneous interaction of various levels of causality and the pros and cons of purely statistical vs. mechanism-based modeling.

Though it might seem impossible to compress such a range of topics into about 200 very readable pages, Jenkins succeeds in providing a survey that might be of equal interest both for the curious reader in search for a popular state of the art discussion of the nine mentioned topics and for the methodologically-minded scholar looking for an introduction to the beauty and perplexities of biomedical research. Footnotes are kept to a minimum and several suggested readings complement each chapter. Jenkins’s approach might well be deemed “ecological”: though he clearly favors certain approaches, his main concern throughout the book is to show us how many of them proliferate now in his field and what sort of results they yield. Only by taking all this into account will we be able to qualify our trust in the alleged scientific grounds of many policies currently under discussion. In other words, the idea of informed consent should be generalized as to encompass (and legitimate) every public decision on environmental and medical matters.

Though Jenkins’ case is articulated and convincing, it might be also a bit puzzling. We may well be aware of the difficulties of attaining conclusive results in the biomedical sciences, but to whom are we rely on to assess them? Jenkins’s implicit assumption seems to be that there will always be non-partisan scientific experts to provide a reliable assessment. Yet, it might happen that controversy among scientists could prevent general audiences from discerning whom to trust. This is a classical dilemma: quis custodet ipsos custodes? Be it what it may, Jenkins’ proposal will probably be part of the solution to this problem.

{October 2004}
{Metapsychology online reviews}

Sheldon Krimsky, Science in the Private Interest. Has the Lure of Profits Corrupted Biomedical Research?, Lanham, Rowman & Littlefield, 2003.

Sheldon Krimsky’s latest book will probably shock those readers who still think of scientific research conducted at non-profit universities as a disinterested activity, exclusively motivated by the pursuit of truth. Among those potentially astonished audiences, you should count most European scholars and, quite likely, a vast majority of American citizens, to whom this book is mainly addressed. It is not that they should care about how much money is being made by an elite of biomedical scientists based at major American universities; the shock comes at the discovery of how this financial incentive might bias their academic behavior, preventing them from cooperating with other researchers (after all, after all, we believe this to be the very purpose of university life) and, more menacingly, influencing their decisions when participating in public committees assembled to assess the efficacy of a drug or therapy, or enrolling us for one of their clinical tests.

Krimsky gathers in eight chapters a significant number of well documented cases which provide ample evidence of the many ways in which biomedical corporations have been conditioning university research since the early 1980s. Funding in exchange for patents constitutes probably the best known issue, but the details of the contracts regulating this transfer are not widely publicized. After a couple of introductory chapters that set the tone of the analysis, the following two explore an array of examples of these sort of agreements, all of which suggest that transforming scientific knowledge into proprietary information constrains the free circulation of ideas that should prevail in academia –according to our classical lore. Indeed, the public discussion of our individual results is still required by most philosophers as a pre-requisite for attaining the status of scientific knowledge. Yet, as Krimsky discusses in chapter 5, most knowledge transfer agreements between universities and corporations restrict access to these results or impose delays on their publication.

Corporate influence might also be felt in Federal advisory boards, in which leading scientists are invited to participate in their capacity as disinterested experts. Yet, as the evidence compiled in chapters 6-9 attests, they might also be directly funded in various ways by biomedical companies whose interest may be put at stake in those commissions. It is often difficult to recruit qualified scientists that are not listed in the consultive boards of one or another corporation, receive from them personal grants or donations for their laboratories or fall under any of the clauses of the federal regulations designed to prevent conflicts of interests within those committees. It might also happen that the scientist is also the entrepreneur, having his own financial interest in the success of the experiments he is conducting. To discount this possible source of bias, it is not unreasonable to expect this piece of information to be disclosed to the readers of his papers –and to the patients on which he might be testing his results. Again, Krimsky shows that it is becoming increasingly difficult for journals and hospitals alike to enforce transparency clauses of this sort.

The final two chapters of this book explore alternative patterns of behavior in academia that would preserve the ideal of universities as the locus of research in the public interest. Krimsky claims that the evidence presented calls for an open debate on the role of American universities, on the basis of which an adequate regulation of their interaction with the corporate world would hopefully emerge. Krimsky’s choice, though not thoroughly articulated in his book for the sake of informativeness, would be quite drastic: “by accepting the premise that conflicts of interest in universities must be subtly managed, rather than prohibited or prevented, nothing less that the public interest function of the American academic enterprise is at stake” (p. 230).

The book is certainly a very readable starting point to open a debate that should not be postponed in the United States, and might help European audiences to look ahead to what it is likely to be a not so distant future. It might be argued, however, that this debate could also benefit from a more ample use of the different approaches that have been developed among science scholars in the last twenty years. Some of them show, for instance, that various interests other than truth have been pervasive in science throughout its entire history. Krimsky assumes an ideal of scientificity that, attractive as it may be, might have been never fully realized. However, the problems he is raising are so serious that it is worth discussing whether it might still help us.

{February 2005}
{Metapsychology online reviews}

Timothy F. Murphy, Case Studies in Biomedical Research Ethics, The MIT Press, 2004.

The ethics of scientific research is certainly a topic of common interest for ethicists and philosophers of science alike, even if many among them still adhere to Merton’s conventional wisdom about scientists being communitarian, universalist and disinterested agents. In other words, not particularly controversial (and even rather exemplary) from a normative standpoint. The advancement of biomedical research ethics, among other disciplines, shows that the pursuit of truth might not always be morally virtuous, as this collection of case studies illustrates at length.

Timothy Murphy has drawn cases from various sources that sometimes go far beyond our ordinary understanding of bioethics in order to achieve a thorough view of the normative dilemmas involved in biomedical research. Of the nine chapters of the compilation, three address general bioethical issues in the context of clinical research (“Informed consent”, “Embryo, Fetuses and Children”, “Genetic Research”); two other ones present more circumscribed topics (such as “Oversight and Study Design”, “Selection of Subjects”, “Use of Animals”) and another three explore frontier domains: “Conflicts of Interests”, “Social Effects of Research” and “Authorship and Publication”. Tracing such a wide-ranging disciplinary map counts among the most significant achievements of this book.

The books are explicitly intended as a “text for instruction” and this certainly accounts for its organization. Each chapter compiles on average 15 case studies, which adds up to 150 cases. Each of these is normally kept to a one-page length, and is presented with an introductory paragraph signalling its point, a couple of references citing sources or further readings when necessary and a few questions intended for discussion. Most cases are known (some are indeed classical), though a reasonable proportion is relatively new. Most of them are real and, save for a few exceptions; almost all are drawn from the wide realm of biomedical research. Each chapter opens with a brief introduction that summarises the dilemmas covered in the cases subsequently presented. There is also a general introduction in which Murphy briefly covers the development of biomedical research ethics and provides some considerations about the utility and risks of case-based discussion.

The proof of a textbook is always use in class, so at this point I can only offer a very preliminary assessment. The instructor should take into account that the information provided in each case is most often just a summary restating the case from the original source with a view to emphasise the implicit moral dilemmas. These are now easier to grasp for the student, but some additional background may sometimes be necessary to illustrate its real complexity –or just to bridge the cultural gap with a non-American audience. The cases are presented without ethical guidelines for discussion: no particular normative stance is assumed by the author (nor on the part of the reader), so a certain familiarity with a number of moral doctrines is a pre-requirement to make a fruitful use of this text. These and other minor caveats aside, we may expect it to become a very useful reference for future courses.

What I miss is a more explicit discussion of the connection between what we may consider positive medical science and the associated normative dilemmas. Once we assume, as the author does, that clinicians may often act as self-interested agents, sometimes as plain rent-seekers, we should consider to what extent the various methodologies applied in medical research are immune to their particular bias. It has been noticed, for instance, that a certain correlation exists in clinical tests between the source of funding (public or private) and their result (for or against new therapies). Should we strengthen the procedures of statistical review to protect the public against some private interests? In spite of its status as the golden rule of clinical research, randomization has been severely contested by Bayesian statisticians on a purely methodological basis, and this certainly would have an impact on the patients when it comes to granting informed consent to take part in a test: should we make the statistical foundations of our methodology explicit for them? Normative dilemmas in biomedical research provide indeed a good opportunity to reconsider its scientific status and reassess the underlying positive/normative dichotomy that often separates bioethicists and philosophers of science.

{July 2005}
{Metapsychology online reviews}

Ruth Macklin, Double Standards in Medical Research in Developing Countries, Cambridge, Cambridge University Press, 2004.

Randomised clinical trials (RCTs) constitute a world-wide acknowledged standard of proof to decide about the efficacy of a drug. Their implementation involves many different ethical dilemmas (e.g., in what conditions it is fair to allocate treatments are random?), but most of these are well known and several agreed guidelines exist to sort them out whenever they appear. At least, in countries where serious institutional review boards (IRBs) are in operation to monitor the trials. But RCTs are also an industrial procedure that the pharmaceuticals should use very often to make their business grow. And since there are many countries in which the absence of serious IRBs is positively correlated with a lower cost of RCTs, there is an strong incentive for the industry to conduct their trials there. There is a single methodological yardstick, RCTs, that guarantees the cogency of the results of the test, making it acceptable for Western regulatory agencies. But there is often a double ethical standard to conduct the trials, since the subjects of the experiment will be treated very differently depending of its geographical location. This is the topic of Ruth Macklin’s path-breaking essay. Her goal is to debunk the various ethical arguments provided to justify the existence of such double-standards and argue for a unified system of ethical guidelines to conduct medical research in our world.

The subject under discussion is mapped in chapter 1. Macklin defines there what she takes to be a developing country in this context: namely, a country in which there are fewer opportunities for the majority of the population to access the successful products of research. This implies that clinical trials provide a unique occasion for them to gain access to new drugs, even in the testing stage. Which also puts these people in a position of inferiority regarding the pharmaceutical companies when it comes to negotiate the details of the trial. The case in point that brought international attention to the problem was a 1997 study of maternal-to-child HIV transmission conducted in a developing country: the contrasting drug was a placebo instead of the best available treatment, as it should have been according the developed world bioethical standards. Macklin introduces here the Declaration of Helsinki, issued in by the World Medical Organization in various amended versions, which she will critically use – together with other similar texts – as a framework for carrying out the discussion in the rest of the book. Her aim is to improve these ethical research guidelines in a way that is “usefully prescriptive without being hopelessly aspirational” (p. 30).

Chapter 2 discusses the problem of the standard of care, which mainly appears in the following circumstances: on the one hand, what sort of drug (if any) should be provided to the control groups in countries where no alternative treatment is available for the study subjects; on the other hand, what level of medical attention should be provided to them beyond the actual goals of the study? Macklin surveys the debate on what should the standards be and presents an ample review of the guidelines provided by various organizations. She undermines here the various arguments for a double standard (e.g., “something is better than nothing”) on considerations both of principle and practical which are expanded in the following chapters.

In Chapter 3, Macklin addresses the issue of distributive justice by contextualising the idea to the area of scientific research. She argues in favour of a moral imperative to provide post-trial benefits to research subjects, drawing from various arguments ranging from equity as maximization to compensatory justice. In this light she reviews many guidelines again, criticizing those that leave room for the opposite conclusion. Yet even if her point is granted, there is the open question of what sort of benefits should be provided. A similar conclusion is reached in the following chapter through an analysis of exploitation. Macklin proposes a definition (p. 101) in which the key point is the lack of adequate compensation to research subjects due to their lack of, so to speak, bargaining power. This definition is extensively contrasted with the guidelines, but now Macklin obtains more concrete conclusions as to the practical implications of the analysis. The entitlement to post-trial benefits is now defended as the proper measure to prevent exploitation. And these benefits appear to be mostly an easier access to the resulting drugs. But Macklin also focuses on the circumstances in which consent may be exploitative – the list of particular circumstances in which exploitation in international research is likely to happen is particularly illuminating in this respect (pp. 118-122).

Chapter 5 then analyses the possible safeguards to guarantee that consent is properly granted and the subjects’ rights are duly protected during the trial. After some illustrations showing the need for such safeguards, Macklin argues for a universalistic conception of consent grounded in individual autonomy against group- or gender- biased definitions, defended on a cultural relativistic basis. In a similar spirit, Macklin defends the convenience of extending the competences of IRBs beyond its actual boundaries, so that they can survey privately sponsored trials abroad when no reasonable alternative is provided.

Chapter 6 focuses on how to make drugs affordable. Its moral implications are already clear at this stage: it would make less defensible the use of placebo in clinical trials conducted in underdeveloped countries and would substantiate the idea of post-trial benefits. Four complementary strategies are discussed: differential pricing in essential drugs; prior agreements to make the drug under trial available in the countries where it is conducted; joint initiatives of international agencies and private-public partnerships to produce affordable drugs; and the manufacture of generic copies of patented drugs for poor countries. Macklin presents different examples of each strategy, emphasizing their more positive prospects.

Chapter 7 returns to matters of principle and restates the case already made using the human rights vocabulary, acknowledging its role as a global standard for international organizations. The eighth and final chapter discusses how to develop research guidelines in accordance with all these considerations, using a quite realistic approach.

Macklin’s effort deserves all praise since she takes into account most of the many possible approaches to her subject and builds a unified and coherent case. Though Macklin navigates at ease in the endless details of the various declarations and proposals discussed, it is not difficult to get lost: the analysis is necessarily brief to keep the essay’s extension within reasonable limits, so many arguments are just outlined and the reader is referred to an ample bibliography to complete them. In this respect, a general references section (instead of one at the end of each chapter) would have been helpful. Yet, the thorough index appended somehow compensates for this and makes the book really accesible. All in all, it is a great survey of a terribly complex issue and it will greatly improve its discussion from now on.

As to the cogency of Macklin’s proposal of a unified standard for medical research, it is difficult not to be sympathetic and the arguments she provides may well ground a wide consensus. Yet, this is a book in which bioethical discussion very often yields policy recommendations, and in this respect I sometimes miss a more concrete discussion of how these would work under different circumstances. Since case studies are for Macklin a good enough ground to build her arguments for or against different policies, I would have liked a case-based analysis of the efficacy of her own proposals, i.e., one in which agents are not motivated by ethical considerations alone but also by their particular interests in the many scenarios in which these proposals should be implemented. Obviously, this is too much asking of a book which is mostly intended as an essay in applied ethics. Yet, when this field is expanded to encompass all the circumstances that she (wisely) takes into account, the argument necessarily becomes something more than ethics and a more interdisciplinary discussion would do much to strength her conclusions, making them more credible. Anyhow, this is a pioneer work and it is fair to say that it just makes this very discussion possible.

{August 2006}
{Metapsychology online reviews}

Shaili Jain, MD, Understanding Physician-Pharmaceutical Industry Interactions. A concise guide, N. York, Cambridge University Press, 2007

Shaili Jain does not need much justification for writing this book: if the pharmaceutical industry is allocating nearly $100,000 and one representative for every eleven practicing physicians in the United States, these latter should ask themselves whether such investment has any effect on their prescriptions. At least, there is evidence that their patients (and often the taxpayer too) would want them to. There is indeed an extensive literature about consequences of pharmaceutical marketing on physicians, published not only in medical journals, but in many other social sciences outlets. It seems though that most doctors consider themselves impervious to the advertising strategies of the industry and Shaili Jain knows that they won’t spend much time learning about them.

This book offers to health care professionals a fast and frugal understanding of these strategies, as they are implemented in the United States: each chapter is about four pages long, of which the analytical presentation of the author’s case takes at most three. In addition there are quick fictional vignettes of each situation analysed, bullet point summaries and an updated reference list. Here goes a list of the topics addressed.

The first two chapters state the author’s main thesis: there is serious evidence that industry gifts create biases that influence physicians’ prescriptions and this has ethical consequences regarding their obligations to their patients. The following three chapters discuss the more prominent ways to create these biases. Namely, through medical detailing (pharmaceutical representatives visiting doctors to present their products), informal teaching to physicians in training, and also sponsoring clinical research to be later published in scientific journals. In chapters 6 and 7 Jain ponders the benefits and disadvantages of these sophisticated marketing mechanisms and provides a list of suggestions to constrain the promotional dimension of industry sponsored events. She offers a brief remainder of the existing professional guidelines about the topic, which are reproduced at length in a 60 pages closing appendix.

Chapters 8 to 11 deal with the public understanding of the interactions between physicians and the pharmaceutical industry. In chapter 8 Jain summarises evidence showing that patients often don’t know how many gifts their doctors receive from the industry and when they are informed, they do not approve of it. When patients receive medication samples as gifts themselves, they tend to overlook the inferior standards of care they are often associated with (physicians are often unaware too). Chapter 10 briefly explores the possibility of applying federal antikickback laws to punish pharmaceutical companies and physicians for exchanging gifts for prescriptions. Finally, in chapter 11, Jain considers the pros and cons of direct-to-consumer advertising of prescription drugs. The book closes with a glimpse of the situation in countries other than the USA and a brief list of internet resources on the topic.

Jain seems to be arguing namely to raise the awareness about the consequences of pharmaceutical marketing among health care professionals. Her review of the literature is often too quick, and sometimes may seem unconvincing or inconclusive. At least, if we compare it with the more “partisan” approaches which abound in this field (either for or against “Big Pharmas”). Yet the book is rich in checklists which allow the physician to ponder the dilemmas she is facing in her daily practice. This self-assessment may not automatically correct her biases (psychologists have experimentally documented our resilience to this kind of corrections), but may open a more informed discussion among health care professionals in which the possibility of biases is not discounted ex ante, as it usually happens now. Perhaps pharmaceutical companies should be compelled to include this book in their catalogue of promotional gifts for the coming years in order to see how it contributes to their sales.

{January 2009}
{Metapsychology online reviews}