Mostrando entradas con la etiqueta medicina. Mostrar todas las entradas
Mostrando entradas con la etiqueta medicina. Mostrar todas las entradas

20/4/18

Jessica Flanigan, Pharmaceutical freedom, Oxford University Press, 2017


Most academic philosophers live in a world of pharmaceutical paternalism: new treatments are subject to premarket approval by State regulatory agencies, and patients will only be able to access them through medical prescription. Outside academic philosophy, there has been a long tradition of pharmaceutical libertarianism, advocating for allowing patients to take their risks with experimental treatments without State or medical interference. Precisely because this tradition has had almost no philosophical echo, Jessica Flanigan’s Pharmaceutical Freedom was a necessary book. Its broad claims and intuitions are not new. The real originality lies in the thorough examination and defence of the right to self-medicate from the standpoint of contemporary moral philosophy.
  
Flanigan grounds her arguments on the patient’s authority in knowing what will promote her overall well-being and in deciding what to do, with an original twist: she shows that supporters of informed consent should also endorse self-medication, as it is based on the same foundations. She criticizes regulatory paternalism for failing to adequately protect public health: informed self-medication could do better. Moreover, pharmaceutical regulators “wrongfully kill patients by withholding access to investigational drugs”, until they are approved. Drug prescription is equally objectionable for restricting the right to die, the right to use recreational drugs, the right to self-enhancement and the right to use pharmaceuticals for non-medical reasons. Flanigan defends that patients should “develop drugs outside the formal mechanisms of the approval process, disobey pharmaceutical regulations, and protest existing policies” (p. 165), even if they do not have the support of a majority of voters (“biased against rights of self-medication”). If, at this point, you are wondering whether pharmaceutical companies do have any particular moral obligation towards patients, Flanigan defends that it is an industry like any other: there is no reason to expect that they provide affordable products. Pharmaceutical marketing (e.g., direct to consumer advertising) should be deregulated, such as any other instance of paternalistic health regulation. Tort law provides enough defence for pharmaceutical consumers to stand against any industry misdeed.

These are the claims that Flanigan makes in her book, and I think the author deserves all the praise to make them as boldly and straightforwardly as possible. Most of these claims, although with different justifications, have been around since the passage of the 1962 Food and Drug Administration Act. It established a pre-market approval system for drugs on the basis of the safety and efficacy they showed in randomized clinical trials. Flanigan surely draws on these libertarian/pro-industry sources (e.g., W. Wardell and L. Lasagna are cited; T. Stossel is mentioned in the acknowledgements), but she constructs arguments that rely, to an unprecedented scale, on principled philosophical considerations (after the steps of Allen Buchanan, Robert Veatch, etc.). Nonetheless, Flanigan has also a policy proposal: a supervision system for pharmaceutical markets. Instead of pure market control (customers select the good treatments buying them), in the best libertarian tradition, or ex post withdrawal of the dangerous compounds (Wardell and Lasagna’s approach), Flanigan defends a certification system, in which a public agency tests the treatments already sold in the market and assesses their safety without gatekeeping powers.

I leave to moral philosophers the discussion of her more principled arguments and, as a philosopher of science, let me take issue instead with this latest proposal. My general contention is that Flanigan tends to overstate her moral claims at the expenses of every other consideration. A case in point is precisely the certification of drug safety.  For Flanigan,  “Drug safety is a normative judgment that requires knowledge about how the risks and side effects of a drug fit into a patient’s life as a whole” (p.10). The 1962 FDA Act definition of safety linked it to efficacy as shown in one particular experimental design: randomized clinical trials should establish whether a treatment for a given condition would reliably have certain effects. This is the positive concept of safety: the choice of a treatment outcome might be normative, but regulators care about it being predictable. Flanigan claims there is something more to safety: a drug may be unsafe for the FDA (e.g., having known adverse effects) and yet a patient may think it is safe for her to take it and, according to Flanigan, she should have the last word about it.  Flanigan provides three arguments about why people can consent to drugs that carry known (and unknown) risks (p.24), showing how consent to risky alternatives (rejecting treatments, participation in phase I trials) is considered acceptable, and yet it seems unjustified to consent to risk thresholds below FDA-safety. So why not leave the ultimate assessment of safety up to the patients?

This is Flanigan’s certification proposal: let regulatory agencies certify the predictable risks of a treatment and leave to patients the informed decision to take them. On purely normative grounds, I think this is a very persuasive idea for anyone with even a minimal anti-paternalist inclination. The problem is, of course, the positive implementation, about which Flanigan provides almost no detail. Her intuition is that for the majority of patients who value their health, not much would change: they will rely on certification, while the most desperate/daring patients will trust their own judgment (p. 62). But I disagree here: the devil is in the details. Randomized clinical trials are long and complicated experiments, often involving thousands of patients, and completing them usually takes years. Assuming that Flanigan’s system adopts the current evidential yardstick, certification will be equally slow. There will be many non-certified systems in the market for which patients will only have the non-certified information provided by the manufacturer. Patients in need of these treatments will have to trust the honesty of the manufacturing company in reporting risks (p.26), and litigate if, after trying the drug, she feels cheated: according to Flanigan, tort law provides a better protection for her rights than any pharmaceutical regulator (p. 221).

I doubt it. For a start, there is an extensive academic literature on the misdeeds of pharmaceutical marketing that should give us some pause about its honesty. This literature is simply absent from the two sections in which Flanigan discusses the topic (pp. 209-217). Instead, pro-industry views are presented on a positive note, giving them, I fear, more epistemic weight than they deserve. E.g., I was intrigued by an unusual reference on the positive effects of direct-to-consumer advertising (p. 211, footnote 13) for which just the title was given and a long Proquest link. Searching on Proquest, I found that the paper was published in the “Web Exclusives” supplement of a journal, with some very serious scholars as lead authors and some co-authors from a marketing agency. After reading Sergio Sismondo’s work on pharmaceutical publication planning, I would have expected Flanigan to add some caveats on the reliability of such a source (and contrast it with more standard sources on the topic).

But even if the libertarian pharmaceutical consumer cannot trust the manufacturer, if she feels cheated after receiving the non-certified treatment, she can always sue for dishonest reporting about risk. My question is: on what grounds can she contest the honesty of the non-certified brochure? On the one hand, there are many evidential standards that can be used to argue that a drug is safe/effective, ranging from clinical trials with different designs to observational studies or simple expert judgment. If the industry is self-serving in choosing the evidence reported in the brochure, how can a court adjudicate whether the information was accurate? On the other hand, given that testing treatments involve long and expensive studies, how can the dissatisfied libertarian patient ground her legal claims? Judges and patients may both defer, of course, on the certification agency test as a benchmark, but then we would be almost back at the status quo: which company will dare to launch a product without conducting long clinical trials, for fear of litigation? 

This are not mere counterfactual scenarios: this is the history of pharmaceutical markets. For example, legitimate British manufacturers in the 1930s were demanding a regulatory intervention in order to protect themselves against the rogue competitors who sold fake drugs based on pretence tests, undermining their own sales. Fraud prosecution offered little protection (against Flanigan’s optimism), because it was difficult to prove fraud in court without an evidential benchmark for authenticity. Again, I cannot help feeling that Flanigan cherry-picks the evidence that supports her case. She cites uncritically the usual bunch of old econometric studies that provide ammunition against our current regulatory system (Peltzman, Temin, etc). Yet, the key concept of Dan Carpenter’s landmark monograph on the FDA, a thick volume of analytical social science published less than a decade ago, is dispatched in just one sentence (p.127).

Summing up, there is a significant gap to bridge between Flanigan’s normative understanding of drug safety and the practical implementation of a certification system for “positive” safety. Flanigan is at her best in the discussion of moral principles (which is 2/3 of her book), but really does a poor job when it comes to policy recommendations (the reminding 1/3). I have been clearly unfair to her work in focusing on this latter aspect, but, I think, it is for a good reason. If I were a libertarian patient willing to dismantle the FDA, I would want some reassurance that we won’t see a regression to the world of unpunished pharmaceutical frauds of the early twentieth century. Moral argument, in other words, is not enough for policy action. But we should be grateful to Flanigan for articulating the libertarian case so well and making it part of our philosophical conversation on the pharmaceutical world.

{March, 2018}

5/4/15


Franklin G. Miller, Luana Colloca, Robert A. Crouch, Ted J. Kaptchuk, The Placebo: A Reader, Baltimore, Johns Hopkins University Press, 2013

The "reader" genre is becoming more difficult today than in any previous decade: in the pre-digital repositories age, compilations granted easy access in print to papers, otherwise difficult and expensive to obtain. Nowadays, we will only buy such compilations if they combine an excellence of editorial taste and readability that beats the temptation of downloading our own selection directly from a journal archive.  In this regard, I must admit that the editors of this placebo reader have succeeded in producing a volume worth buying. 
  
The book compiles 52 papers on the placebo effect divided in four sections. Eight articles feature in the first one, on the concept and significance of the placebo effect. 30 more are classified under four headings in the second section, experimental studies of the placebo effect: the headings are pioneering efforts, psychological mechanisms neurobiological mechanisms and contextual factors. The third and final section, on the ethics of using placebos, presents the last 14 papers about research and clinical practice. The papers are chosen and presented in such a way that the compilation reads as a historically motivated introduction to our current understanding of the placebo effects.
The uninitiated reader will probably appraise the placebo as a treatment without active ingredient that nonetheless makes (some) patients improve (e.g., sugar pills). As Ted Kaptchuk observes in his introduction, this is a relatively modern concept. Using placebos implies that we are somehow able to differentiate between effective and ineffective treatments and such a distinction could only be properly quantified with the emergence of clinical trials in the 1940s. There was an initial enthusiasm about the healing power of placebos that gradually vanished with more sophisticated analyses (documented in the anthology with papers from the 1980s and 1990s): the statistical data of most clinically relevant variables tend to regress from extreme values (disease) to the mean (health) of their distribution, and we can only take properly into account this spontaneous improvement if we compare in a trial a group of patients treated with a placebo with another one with no treatment at all. Taking all this into account, the mainstream view today is that the only placebo effect statistically documented appears when measuring patient reported outcomes, such as pain. The papers complied in the first section document how this view emerges.   

It is worth recalling here that clinical trials were introduced in medicine as a yardstick for assessing the effective of treatments without a real causal understanding of why they were effective. E.g., the underlying mechanism of the antidepressant action of benzodiazepines was understood in the 1970s almost two decades after the first trials, when Valium was already one of the best selling drugs of the past century. Trials often guided our investigation of such mechanisms, showing how a drug operated under a range of different circumstances. In this respect, placebos would be like any other treatment: we lack a "robust and comprehensive" (Kaptchuk) theory, but there is a growing body of experiments documenting how placebos work. First, there are psychological mechanisms, among which the most prominent are behavioral conditioning (often unconscious) and expectations (usually conscious) induced verbally or, e.g., through social observation. Through a number of experimental designs we learn how these mechanisms operate and the physiological responses they trigger (e.g., the release of opioids). Then there are neurobiological mechanisms underlying placebo, illustrated in a number of experiments supported by various forms of brain imaging. Finally, there are contextual factors, often related to the interaction between physicians and patients in a given setting. 

Half of the third section, on the ethics of placebo, hinges on clinical trials as well. Here the approach is mostly methodological: to what extent do we actually need placebo in order to ground solid experimental designs? More precisely, do placebos provide a real benchmark to gauge the efficacy of a new treatment? The obvious ethical implication is that, were the response negative, there would be no reason to use a placebo instead of an active treatment (if there was one) as a comparison. Moreover, since placebos partly operate through the patients' expectations, it is an open question how much shall we deceive them about the (lack of) treatment they are receiving. There is some evidence about placebos working when they are almost openly presented as such. And there is also evidence, presented in the second half of this section, about physicians prescribing placebos outside trials and a discussion about the ethics of such a practice. 

The book closes with a paper by Miller and Colloca, two of the editors of the volume -there are 10 papers co-authored by, at least, one of the members of the editorial team, so there is no pretence of neutrality in the compilation. Their conclusion summarizes somehow the agenda this volume seems to promote: for certain conditions, placebo might actually be an effective treatment; if there is evidence gathered in well-designed trials and the nature of the treatment is properly disclose to the patient, it is acceptable to prescribe it. Hence, acupuncture for pain relief in various conditions could be legitimately prescribed on evidence-based grounds. But, for the time being, no other placebo meets such a scientific standard. 

On a more general note, I'd say that a major thread in this book is that it contributes evidence to ground quite a paradoxical intuition: the mere act of diagnosing a patient and administering a treatment (at least for a few conditions) has effects that break the equivalence between "placebo" and "lack of treatment". My favorite illustration in the book is an trial with Kaptchuk as first author (pp. 226-32) testing different "treatments" for the irritable bowel syndrome: being in a waiting list (measuring patients' response to observation and assessment); sham and real acupuncture (placebo) and an augmented placebo: the needling was accompanied by a scripted positive interaction with the physician. The trial showed that these three components add up progressively, reaching a maximum effect with the augmented placebo, reaching a clinically significant effect in the treatment of the condition. 

In the traditional approach to trials, the preferences of patients were considered a source of bias, since they could make a difference on the outcome. The evidence gathered in placebo research shows that, except for pain, there is no trace, so far, of a significant effect of the patients’ expectations on the treatment outcome. Perhaps this volume should prompt us to reconsider the status of blinding as a debiasing method: its usual justification is precisely that it controls for placebo effects derived from the patients preferences about treatments. Making them entirely alike breaks any systematic correlation between such preferences and the treatment outcome. But if there is no placebo effect for most conditions, perhaps we should reappraise blinding as a method to enforce the treatment protocol: since some patients would drop off the trial if they knew they were receiving an unwanted treatment, blinding secures their compliance, independently of the placebo effect. Clinical trials are indeed strategic interactions between agents with different, sometimes conflicting, interests that we should take into account in designing the trial. Controlling for some of these interactions (more than the placebo effect) might be the real justification of masking devices. In one of the compiled papers, R. Temple and S. Ellenberg contribute another argument in this same vein against active-control equivalence trials (p. 258): if you compare a drug against placebo, you have every incentive to enforce compliance with the trial protocol, since every deviation will usually reduce the differences between treatment groups, making your drug equivalent to a placebo. If you make a comparison with a standard treatment in order to prove lack of difference, there are weaker incentives to enforce protocol compliance. In other words, placebos may play a role in making both patients and researchers alike play by the rules of the experiment.

Two final positive comments. One surprising feature of this collection is how well it reads: each section is preceded by a short (but incisive) introduction intended as a road map of the papers to come. These are short and clear, and very accessible for the lay reader. The design of the experiments, their findings and the issues they raise are often so puzzling that the collection becomes engaging: I found myself eager to know whether an experiment had passed the test of replication, whether counter-arguments existed, if there was a final word on a topic. The papers are selected and ordered in such a way as to elicit this sort of engagement. Another surprising trait is the size of the volume (10.9 x 8.4 x 0.9 inches): it may initially look difficult to handle (in this age of palm-sized readers), but I found it very pleasant to work with.
{January 2014}

4/3/14

Raffaella Campaner, Philosophy of medicine. Causality, Evidence and Explanation, Bologna, Archetipo Libri, 2012

For more than a decade now, there has been a growing interest in the philosophy of medicine as a scientific discipline. Already in 2005, Raffaella Campaner published a monograph in Italian on causality and explanation in medicine (Spigazione e cause in medicina: un’indagine epistemologica) showing how philosophy of science could be successfully applied to biomedical research. Throughout this decade, Campaner published a series of papers in English on the same topics that are now compiled in the reviewed volume. Most of these papers were originally published in edited collections or journals where medicine was not the central topic, so re-publishing all together in a single volume makes sense for the interested reader. Moreover, the Italian publisher has produced a decently edited but inexpensive book, so all in all philosophers of medicine should welcome it.

Campaner has gathered here 9 papers plus an introduction. Their structure is somewhat similar: the author presents different philosophical positions (mostly on causality, but also on explanation) and proceeds to illuminate them with medical case studies, arguing on this basis for her own claims. The reader will find thus an introduction to the following accounts on causality: mechanistic (Salmon, Machamer-Darden-Craven, Glennan), interventionist (Woodward) and manipulative (Price and Menzies), with a brief digression on counterfactuals (Lewis). Despite featuring on equal rank in the book’s title, we do not find introductory accounts of philosophical theories of explanation and evidence. Campaner considers instead plenty of medical explanations and evidences and see how they may fit in the different philosophical accounts of causality presented. Among her case studies, two of the most detailed are on deep brain stimulation (a therapy for Parkinson’s disease) and anti-AIDS treatments. Campaner deals also in several papers with epidemiological and psychiatric causation.

The book puts forward a pluralistic perspective on causation, showing how in actual medical practice we may find all the above mentioned approaches complementing (rather than competing with) each other. The choice often depends on the methods implemented and the context of implementation. The author does not try to construct a principled argument for causal pluralism: as she acknowledges, “lots of work is still to be done before a plausible and coherent view will be settled on and shared” (p.60). The strength of her argument is empirical: there is no evidence that a “one size fits all” concept of causation can cope with the diversity of causal approaches at work in medical practice. However, Campaner also draws on a conceptual insight emerging from this diversity: diseases would be multilevel phenomena (ranging from cells, molecules, tissues upwards to the whole organism) and medicine (siding here with Schaffner, p. 11) would be a set of middle-range theories coping with them. Campaner adopts here a sort of meta-philosophical instrumentalism regarding such deeply entrenched methodological divides such as the one opposing reductionism and anti-reductionism: as she illustrates in chapter 7, both strategies have been fruitful in medicine and both might make sense contextually. In this respect, I think is worth noticing how difficult it is to sustain even moderately pluralist stances about medical causality such as the Russo-Williamson thesis –according to which we would need mechanistic and probabilistic evidence to properly ground causal discoveries. Yet, as Campaner argues in chapter 2, medicine has been quite capable of making progress without mechanisms and yet, when we have them, we often need manipulative evidence, in addition to statistics, to properly ground them.

Campaner constantly reminds us that her pluralism does not “amount to treat all available methodological options as equal in value” (e.g., p. 133), but the book focuses mostly on cases where there is more complementarity than straightforward competition between the alternatives considered and all of them are worth, at this point in time, of scientific consideration. Historically, though, medicine has not been as peaceful as it might seem today. In The Rise of Causal Concepts of Disease (2003), for instance, K. Codell Carter has forcefully argued that scientific medicine began with the adoption of the etiological standpoint, the view that every disease has a single cause which is both necessary and sufficient for the disease, showing how this approach was crucial for progress in its treatment. Even today, I would say that medicine is not really pluralist when it comes to decision making about new therapies: we still rely on their success in randomized clinical trials as a rule. Of course, trials might be interpreted from different causal stances, but not all of them are equally captured in their design: mechanistic knowledge, for instance, does not currently qualify the value of a trial in most hierarchies of medical evidence.  In other words, as of today, philosophical pluralism about causation may faithfully reflects the way medicine is practiced, and methodological diversity may be in itself a fruitful research strategy. But I think Campaner’s claim would have been more balanced if it also considered cases in which there was open disagreement about causality between competing research agendas.

My major qualm with this volume is that the papers were not edited for the compilation. Reading it from cover to cover might be a bit reiterative sometimes since the same items are often revisited in different chapters. However, it makes it really suitable for use in undergraduate courses, in particular when teaching philosophy of science to medical students, since most concepts are explained in an accessible manner detail and illustrated with theories they will be certainly familiar with. The name index at the end is particularly helpful in tracing different approaches throughout the book and keeping the original abstracts at the beginning of each chapter is equally useful to guide the uninitiated reader. Campaner’s is thus not only a good philosophy of science in practice book, but also a very accessible book in itself.

{October 2013}
{International Studies in the Philosophy of Science 27.4 (2013), 456-458}

11/4/12

Catherine Will & Tiago Moreira, eds, Medical Proofs, Social Experiments. Clinical Trials in Shifting Contexts, Farnham, Ashgate, 2010.

More than half a century ago now, physicians began to struggle with how to assess the efficacy of treatments. As the late Harry Marks documented at length, around the 1950s the two alternatives considered for making these assessments were the case-based judgment of individual experts and the results of randomized clinical trials (RCTs). However, after only a few decades, the RCT reached the apex of the hierarchy of clinical evidence, where it remains despite the objections of a number of dissenting doctors, philosophers and sociologists. The compilation edited by Catherine Will and Tiago Moreira brings us a selection of the most recent sociological literature on medical experiments. It is interesting to note that, as the editors themselves present it, this book constitutes a vindication of case-based reasoning against the purported generality of RCTs. In these latter, we assume that we are dealing with a representative sample of patients and a standardized treatment protocol, allowing us to generalize our conclusions beyond the trial. The case studies compiled in this book question the possibility of such generalization: as the editors conclude, information about how clinical trials are organized and carried out goes beyond reporting of methods and is crucial for critical interpretation of evidence. This information should be compiled precisely through case studies, bridging the gap between the agents defined in the research protocol and the communities and contexts where these protocols are implemented.

Unlike other edited collections of case studies, this one aims at constructing a systematic argument. In this respect, Will and Moreira have done a wonderful editorial job, making explicit the threads between the different chapters in their introduction and conclusion and in short prefaces to each of the three parts into which they divide their compilation. In part I, “The Practices of Research,” three case studies, by Stefan Timmermans, Ben Heaven and Claes-Fredrik Helgesson, analyze how researchers struggle with trial protocols, either adapting them to their own goals, resisting them if they conflict with these latter or supplementing the protocols with their own ad hoc methods in order to assure that trials are completed. The editors present their own papers in part II, “Framing Collective Interpretation”. Both deal with the appraisal of trial results by third parties: the medical profession through their specialized journals and the State (the British National Institute for Clinical Excellence). In part III, “Testing the Limits for Policy,” three more papers discuss the use of trials for policy-making purposes. Again, the analyses focus on the role of contexts in policy-oriented trials: the adverse consequences of bracketing contextual information (briefly discussed by Trudy Dehue regarding depression) or the virtues of making the most of it in the trial (Ann Kelly and Alex Faulkner).

This quick summary is obviously guilty of saying very little about the actual the content of the papers. If we list them according to the interventions examined, we find a trial on the use of antidepressants (bupropion) against methamphetamine dependency (Timmermans), a comparison of two lifestyle interventions with medication against a common, chronic condition (Heaven), the controversy on the rosuvastatin trials (Will), the NICE cost-utility analysis of dementia drugs (Moreira), two hybrid trials of an arthritis screening program and of mesh screens against malaria (Kelly), and a recent British prostate cancer detection program (Faulkner).

The general point the editors are trying to make is that the conduct of clinical trials and the interpretation of their results depend not only on their research protocol, but on the intentions of the many agents who, one way or another, are involved in the process. Generalizing the results of a trial beyond their “context of discovery” is something that we can only decide on case by case basis. Indeed, from what they hint in the conclusion (e.g., p. 158), the editors would rather advocate redesigning regulatory trials so that their different stakeholders could have their say.

Emphasizing the ultimate context dependence of RCTs is a point worth making against those philosophers (or perhaps statisticians) who allow no epistemic role for such contextual dependencies of RCTs. But do the contextual dependencies discussed in this volume actually interfere with our ability to identify treatments that are efficacious for the general population? Do we have less reliable trials as a result of these out-of-the protocol interventions, and should the medical community consider alternatives to the RCT ?

Unfortunately, none of the papers in this collection addresses this crucial problem. The one that comes closest is Helgesson’s analysis the practices of out-of-protocol data cleaning in large Swedish RCTs. Helgesson tracks the ways in which data are informally recorded and corrected without leaving a trace in the trial’s logbook, from post-it notes to guesses about the misspelling of an entry. In his view, the trial participants who make such corrections do them in good faith in order to increase the credibility of their results. However, Helgesson explicitly refuses to discuss what sort of errors may be thus introduced in the data, as if “any idiosyncratic shaping of data should be understood as producing biased data and biased results” (p. 52) and we therefore cannot draw any conclusions about the impact of such errors on the interpretation of the study. But psychologists have documented at length how the credibility these practitioners seek is directly connected with confirmation biases, despite Helgesson’s contention: we all tend to accept more easily information that confirms our prior beliefs than disconfirming data. Confirmation biases have been documented in scientific laboratories, for instance, by Kevin Dunbar and his team at Toronto, who have shown as well that experimenters rely on bias-correction procedures from which the reliability of the data stems.

Are these informal practices of data recording and correction threatening the goals of trials as safety and efficacy tests? We know that RCTs do not provide full information about the effects of a drug, as the statistics on adverse effects reported to the FDA show. But, at the same time, regulatory clinical trials have so far been reasonably good at screening off the pharmaceutical markets from toxic and ineffective compounds. If trials were conducted to learn as much as we could about new treatments, perhaps the sort of contextual information provided in these case studies would help. In her chapter, Ann Kelly shows, for instance, how the self-selection of participants in a trial may turn out to be a good thing if the information gathered about this particular group of patients shows how to best implement a medical intervention. However, most RCTs are conducted just to prove certain effects to a skeptical audience (the regulatory agencies). Given RCTs track record of efficacy for regulatory purposes, how would an ethnography of the trial, or any reform of the type we saw Will and Moreira advocate, help the regulator in making his decision? Will it improve our current standards of safety and efficacy? Would it just make the trials more credible to the public?

At any rate, if case studies are to play a role in this re-shaped regulatory process, we ought to require from them the same warrants of impartiality we require from RCTs. A number of well-documented biases interfere in the conduct of trials and we try, at least, to prevent them with devices such as blinding and randomization. If a case study on the conduct of a trial should be taken into account by the regulator, by way of background information, how does this latter know that the report is not biased? Sociologists and anthropologists are presumably as vulnerable to biases as any other researcher involved in a trial, and the case-study should incorporate methodological caveats preventing partiality. Will and Moreira do not mention any such safeguards in their conclusions, but if their proposal ever succeeds, I am sure this is a problem they will have to address.

{December 2011}
{Theoretical Medicine and Bioethics 33.5 (2012)}

15/4/09

Jill Fisher, Medical Research for Hire. The Political Economy of Pharmaceutical Clinical Trials, Rutgers University Press, 2009

In Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials, Jill Fisher presents the results of 12 months of fieldwork conducted around 2003 in two major cities in the southwestern United States. During this period, the author analyzed "more than twenty" for-profit research organizations performing clinical trials for the pharmaceutical industry. The main output is an ethnography of the identities adopted by the different participants in those trials. On this basis, Fisher denounces how unfair to patients this system is.

A clinical trial is a medical experiment in which a new drug is compared to the standard treatment or a placebo administering them to two groups of patients in order to test its efficacy. The American Food and Drug Administration (as most other regulatory agencies around the world since the 1960s) requires statistical evidence derived from clinical trials in order to authorize the commercialization of new drugs. Whereas until the 1990s a majority of these experiments were conducted in public medical centers, nowadays the pharmaceutical industry is contracting most of them with a variety of private companies. In exchange for many billions of dollars, these companies promptly deliver trial results that generate early profitable patents for their sponsors. The protocol of the experiment is pre-arranged by the pharmaceutical company, so the contractor can only play with the efficiency of the implementation, particularly in the recruitment and involvement of patients.

Fisher analyzes through interviews and direct observation the different roles involved in the management of these private trials. According to Fisher, driven by purely financial incentives, the physicians in these organizations adopt both of these two distinct roles (chapter 3): entrepreneurial agents (they run their companies) and pharmaceutical emissaries (they implement their sponsors' experimental design). Fisher shows that these two roles set very strict limits on their therapeutic obligations with their patients. Chapter 4 is devoted to research coordinators, whose assignment in the trial is namely to deal with patients (recruiting, screening, obtaining consent) and manage part of the trial bureaucracy. Their professional identity is defined mostly in terms of their obligation to care for the patients (many of them are former nurses and a majority are women). Again, their corporate responsibilities often constrain their care duties. In chapter 5, Fisher analyses the monitors appointed by the pharmaceutical sponsors to audit the trial and prevent frauds. This is a feminized profession too, with a very demanding administrative task and a multifaceted symbolic role, often contradictory: "protector of the public health, coordinator's 'best friend,' and scapegoat for the problems of outsourcing".

In chapter 6 Fisher profiles the types of patients most likely to be involved in private trials. In research conducted on healthy subjects to test the safety of a new drug, most of the volunteers are men from a minority (very often Hispanic), seeking a financial reward. In efficacy trials on patients, there is an increasing participation of white middle class women, who are sought by the companies because they are available and compliant with the protocol. According to Fisher, most of them are "neoliberal subjects motivated by their social and economic positions to benefit the best they can from the system of drug development" (p. 178). In the two following chapters Fisher tries to show that the informed consent that such patients sign is often conditioned by the weakness of their positions in American society (poor, uninsured, uneducated). Moreover the therapeutic benefit they derive from their participation in the trial is often minimal. This hinders their compliance with the trial protocol and puts the "managers in a difficult ethical position to persuade them to comply.

Medical research for hire combines indeed ethnography and ethics. The former prevails: the book is rich in quotations from the many interviews conducted by the author and we get to know how the participants in the private clinical trials studied perceive themselves. However, the author only visited a minor fraction of the many organizations conducting trials in the USA and had unequal access to the different types of participants. Her description may ring true, but I am afraid further studies are necessary to confirm that it is representative of a broader pattern. Informative as this ethnography is, its theoretical analysis is not satisfactory, at least in my view (the authoritative endorsements in the cover say otherwise). A substantial part of the analysis consists in glosses over the quotations, in which the author generalizes about her subjects as if they represented the "social and economic positions" of participants in trials across America. Her analysis is very local though (just two major southwest cities) and I would have appreciated a situated analysis in which the particular circumstances of the participants explained their testimonies. The author appeals instead to the "political economy" of "medical neoliberalism", understanding these concepts in a vaguely Foucaultian sense: pharmaceutical capitalism would be constraining the choices of trial participants to a point that often distorts their perception of their own actions. Perhaps it is just an effect of my excessive exposure to experimental social sciences (or actual political economy), but I miss an actual explanation of how this is happening.

I do not find the ethical analysis much deeper. Fisher shows that the discourses of the professionals involved in clinical trials often misrepresent the situation, making it better for the patients than it actually is. I will not dispute this (and it is certainly good to try to inform them). But I guess that Fisher's ethical target is more the for-profit conduction of clinical trials than the discursive misrepresentations of their conductors. Is there an ethical standard for private clinical trials? I guess the author is not very confident about it, but I would have appreciated a more explicit and articulated answer.