How Pharmaceutical Industry Employees Manage Competing Commitments in the Face of Public Criticism

The pharmaceutical industry has been criticised for pervasive misconduct. These concerns have generally resulted in increasing regulation. While such regulation is no doubt necessary, it tends to assume that everyone working for pharmaceutical companies is equally motivated by commerce, without much understanding of the specific views and experiences of those who work in different parts of the industry. In order to gain a more nuanced picture of the work that goes on in the “medical affairs” departments of pharmaceutical companies, we conducted 15 semi-structured interviews with professionals working in medical departments of companies in Sydney, Australia. We show that this group of pharmaceutical professionals are committed to their responsibilities both to patients, research participants, and the public and to their companies. Despite the discrepancies between these commitments, our participants did not express much cognitive dissonance, and this appeared to stem from their use of two dialectically related strategies, one of which embraces commerce and the other of which resists the commercial imperative. We interpret these findings through the lens of institutional theory and consider their implications for pharmaceutical ethics and governance.     

Off‐Shoring Clinical Research: Exploitation and the Reciprocity Constraint

The last 20 years have seen a staggering growth in the practice of off‐shoring clinical research to low‐and middle‐income countries (LICs and MICs), a growth that has been matched by the neoliberal policies adopted by host countries towards attracting trials to their shores. A recurring concern in this context is the charge of exploitation, linked to various aspects of off‐shoring. In this paper, I examine Alan Wertheimer's approach and offer an alternative view of understanding exploitation in this context. I will suggest that the justification for the enterprise of research is largely dependent on its integration within a health system from which participants regularly benefit and I argue that an attention to a principle of reciprocity will enable us to better recognize and address exploitation in international research.     

On the Alleged Right to Participate in High‐Risk Research

Reigning regulatory frameworks for biomedical research impose on researchers and research ethics committees an obligation to protect research participants from risks that are unnecessary, disproportionate to potential research benefits, and non‐minimized. Where the research has no potential to produce results of direct benefit to the subjects and the subjects are unable to give consent, these requirements are strengthened by an additional condition, that risks should not exceed a certain minimal threshold. In this article, I address the question of whether there should be limits of permissible risks in non‐therapeutic research involving competent and healthy subjects. Some commentators argue that competent and informed individuals should have a right to participate even in extremely risky research and that research ethics committees should never reject studies because they are too dangerous. To use David Shaw's expression, competent volunteers should have ‘a right to participate in high‐risk research’. I argue that this idea is ill‐founded, as it does not take into account the social mission and complex collaborative nature of research practice as well as the inequity of power between researchers and subjects. Imposition of limits on permissible risks for healthy volunteers is justified by the need to protect research enterprise and the need to protect the weaker party, namely the subjects. Also, I suggest that the best way to set boundaries on research risks is to leave the judgment of risk acceptability to research ethics committees.     

The Vulnerability of Study Participants in the Context of Transnational Biomedical Research: From Conceptual Considerations to Practical Implications

Outsourcing clinical trials sponsored by pharmaceutical companies from industrialized countries to low‐ (middle)‐income countries – summarized as transnational biomedical research (TBR) – has lead to many concerns about ethical standards. Whether study participants are particularly vulnerable is one of those concerns. However, the concept of vulnerability is still vague and varies in its definition. Despite the fact that important international ethical guidelines such as the Declaration of Helsinki by the World Medical Association or the Ethical Guidelines for Biomedical Research Involving Human Subjects by the Council of International Organizations of Medical Sciences refer to vulnerability as ethical principle, each of their approaches are different. To overcome these shortcomings, we analyze and unite different approaches of vulnerability and develop practical criteria in order to operationalize the concept especially for the context of TBR. These criteria refer to the context of a study as well as the characteristics and the current living situation of study participants. Based on a case study of an HIV‐vaccine‐trial conducted in India we demonstrate how those criteria can be applied in a retrospective way to identify potential ethical conflicts. The criteria can also indicate a prospective function for ethical pre‐assessment. For this, we provide an outlook for three major topics: 1. Vulnerability as a normative concept: Different ways of protection; 2. The relevance of transparency and 3. Vulnerability as an instrument to increase decision participation of human subjects.     

Human tissue for in vitro research as an alternative to animal experiments: a charitable "honest broker" model to fulfil ethical and legal regulations and to protect research participants

Research with human tissue offers the possibility not only of improving preclinical pharmaceutical research and safety assessment, but also of the substitution of some animal experiments. Surgically removed human tissue is discarded after pathological evaluation. This tissue would be of enormous value for research, especially in the pharmaceutical branch, if it were readily available in an ethically and legally approved manner. But there are public concerns about the use of human tissue, especially for "commercial" purposes, such as in the pharmaceutical industry. The question is whether the ethical boundaries are sufficiently respected in the course of striving for industrial profit. To overcome this problem, a clear procedure for tissue donation, collection, supply and allocation must be established, which is guaranteed to be independent of special interests. The persisting problem seems to be the lack of an authority which asks for informed consent, coordinates tissue as well as blinded data collection, and supplies research facilities with tissue samples in a transparent manner. Therefore, a charitable, state-controlled foundation acting as an "honest broker" was initiated, to cover the ethical and legal aspects, as well as to protect the research participants in their use of human tissue as an alternative to animal experiments.     

Health Professionals “Make Their Choice”: Pharmaceutical Industry Leaders’ Understandings of Conflict of Interest

Conflicts of interest, stemming from relationships between health professionals and the pharmaceutical industry, remain a highly divisive and inflammatory issue in healthcare. Given that most jurisdictions rely on industry to self-regulate with respect to its interactions with health professionals, it is surprising that little research has explored industry leaders’ understandings of conflicts of interest. Drawing from in-depth interviews with ten pharmaceutical industry leaders based in Australia, we explore the normalized and structural management of conflicts of interest within pharmaceutical companies. We contrast this with participants’ unanimous belief that the antidote to conflicts of interest with health professionals were “informed consumers.” It is, thus, unlikely that a self-regulatory approach will be successful in ensuring ethical interactions with health professionals. However, the pharmaceutical industry’s routine and accepted practices for disclosing and managing employees’ conflicts of interest could, paradoxically, serve as an excellent model for healthcare.     

U.S. Federal Initiatives to Support Biomass Research and Development

This article provides a brief overview of federal initiatives in the United States to support biomass research, demonstration, and development. The interest in the biomass industry and U.S. federal efforts to spur development of, increased production of, and use of biopower, biofuels, and biobased products, collectively known as the "biomass industry", are discussed. A growing level of leadership from the executive branch of the federal government and support by the U.S. Congress are documented. Five important policy drivers that support this heightened emphasis on biomass for power, fuels, and products are identified and discussed. The current status of U.S. dependence on these renewable energy sources is briefly outlined. Federal biomass funding activity for the current fiscal year by the U.S. Department of Agriculture and the U.S. Department of Energy, two major federal participants in research, demonstration, and development for this industry, is briefly outlined. This funding commitment is placed into an overall context of total federal support for all research and development. Finally, the article suggests future market penetration targets for this industry, emphasizes the importance of infrastructure development necessary to support the industry's growth, and notes the payoff from such development for farmers, foresters, rural communities, and the environment.     

Research participation and the right to withdraw

Most ethics committees which review research protocols insist that potential research participants reserve unconditional or absolute 'right' of withdrawal at any time and without giving any reason. In this paper, I examine what consent means for research participation and a sense of commitment in relation to this right to withdraw. I suggest that, once consent has been given (and here I am excluding incompetent minors and adults), participants should not necessarily have unconditional or absolute rights to withdraw. This does not imply that there should be a complete absence of rights, or, indeed, an abandonment of the right to withdraw. The point of this paper is to show that the supposed unconditional or absolute nature of these rights may be self-defeating and so fail to respect the autonomy of participants. In addition, and on a more positive note, I suggest that, attaching certain conditions on the right to withdraw, may better respect the autonomy of these participants by underlining the idea that autonomy is more than mere whim or indifference to the fate of others. On the contrary, research staff are currently unable to 'push' participants, who may merely have logistical difficulties unrelated to the research itself, but who really want to stay the course, for fear of coercing them. Furthermore, researchers now try to 'screen out' people they think may be unreliable to protect the science of the study and so groups at risk of dropping out may be unfairly denied access to research treatments. I conclude that on-going negotiation between the relevant parties could be on balance the only truly acceptable way forward but concede certain important limitations to take into account.     

Predicting the coupling specificity of GPCRs to G-proteins by support vector machines

G-protein coupled receptors （GPCRs） represent one of the most important classes of drug targets for pharmaceutical industry and play important roles in cellular signal transduction. Predicting the coupling specificity of GPCRs to G-proteins is vital for further understanding the mechanism of signal transduction and the function of the receptors within a cell, which can provide new clues for pharmaceutical research and development. In this study, the features of amino acid compositions and physiochemical properties of the full-length GPCR sequences have been analyzed and extracted. Based on these features, classifiers have been developed to predict the coupling specificity of GPCRs to G-protelns using support vector machines. The testing results show that this method could obtain better prediction accuracy.     

Investigating assumptions of vulnerability: A case study of the exclusion of psychiatric inpatients as participants in genetic research in low‐ and middle‐income contexts

Psychiatric genetic research investigates the genetic basis of psychiatric disorders with the aim of more effectively understanding, treating, or, ultimately, preventing such disorders. Given the challenges of recruiting research participants into such studies, the potential for long‐term benefits of such research, and seemingly minimal risk, a strong claim could be made that all non‐acute psychiatric inpatients, including forensic and involuntary patients, should be included in such research, provided they have capacity to consent. There are tensions, however, regarding the ethics of recruiting psychiatric inpatients into such studies. In this paper our intention is to elucidate the source of these tensions from the perspective of research ethics committee interests and decision‐making. We begin by defining inpatient status and outline some of the assumptions surrounding the structures of inpatient care. We then introduce contemporary conceptions of vulnerability, including Florencia Luna’s account of vulnerability which we use as a framework for our analysis. While psychiatric inpatients could be subject to consent‐related vulnerabilities, we suggest that a particular kind of exploitation‐related vulnerability comes to the fore in the context of our case study. Moreover, a subset of these ethical concerns takes on particular weight in the context of genetic research in low‐ and middle‐income countries. At the same time, the automatic exclusion of inpatients from research elicits justice‐related vulnerabilities.     

Post‐trial obligations in the Declaration of Helsinki 2013: classification,reconstruction and interpretation

The general aim of this article is to give a critical interpretation of post‐trial obligations towards individual research participants in the Declaration of Helsinki 2013. Transitioning research participants to the appropriate health care when a research study ends is a global problem. The publication of a new version of the Declaration of Helsinki is a great opportunity to discuss it. In my view, the Declaration of Helsinki 2013 identifies at least two clearly different types of post‐trial obligations, specifically, access to care after research and access to information after research. The agents entitled to receive post‐trial access are the individual participants in research studies. The Declaration identifies the sponsors, researchers and host country governments as the main agents responsible for complying with the post‐trial obligations mentioned above. To justify this interpretation of post‐trial obligations, I first introduce a classification of post‐trial obligations and illustrate its application with examples from post‐trial ethics literature. I then make a brief reconstruction of the formulations of post‐trial obligations of the Declaration of Helsinki from 2000 to 2008 to correlate the changes with some of the most salient ethical arguments. Finally I advance a critical interpretation of the latest formulation of post‐trial obligations. I defend the view that paragraph 34 of ‘Post‐trial provisions’ is an improved formulation by comparison with earlier versions, especially for identifying responsible agents and abandoning ambiguous ‘fair benefit’ language. However, I criticize the disappearance of ‘access to other appropriate care’ present in the Declaration since 2004 and the narrow scope given to obligations of access to information after research.     

Medical Researchers' Ancillary Care Obligations: The Relationship‐Based Approach

In this article, I provide a new account of the basis of medical researchers' ancillary care obligations. Ancillary care in medical research, or medical care that research participants need but that is not required for the validity or safety of a study or to redress research injuries, is a topic that has drawn increasing attention in research ethics over the last ten years. My view, the relationship‐based approach, improves on the main existing theory, Richardson and Belsky's ‘partial‐entrustment model’, by avoiding its problematic restriction on the scope of health needs for which researchers could be obligated to provide ancillary care. Instead, it grounds ancillary care obligations in a wide range of morally relevant features of the researcher‐participant relationship, including the level of engagement between researchers and participants, and weighs these factors against each other. I argue that the level of engagement, that is, the duration and intensity of interactions, between researchers and participants matters for ancillary care because of its connection to the meaningfulness of a relationship, and I suggest that other morally relevant features can be grounded in researchers' role obligations.     

Raising the Barriers to Access to Medicines in the Developing World – The Relentless Push for Data Exclusivity

Since the adoption of the WTO‐TRIPS Agreement in 1994, there has been significant controversy over the impact of pharmaceutical patent protection on the access to medicines in the developing world. In addition to the market exclusivity provided by patents, the pharmaceutical industry has also sought to further extend their monopolies by advocating the need for additional ‘regulatory’ protection for new medicines, known as data exclusivity. Data exclusivity limits the use of clinical trial data that need to be submitted to the regulatory authorities before a new drug can enter the market. For a specified period, generic competitors cannot apply for regulatory approval for equivalent drugs relying on the originator's data. As a consequence, data exclusivity lengthens the monopoly for the original drug, impairing the availability of generic drugs. This article illustrates how the pharmaceutical industry has convinced the US and the EU to impose data exclusivity on their trade partners, many of them developing countries. The key arguments formulated by the pharmaceutical industry in favor of adopting data exclusivity and their underlying ethical assumptions are described in this article, analyzed, and found to be unconvincing. Contrary to industry's arguments, it is unlikely that data exclusivity will promote innovation, especially in developing countries. Moreover, the industry's appeal to a property rights claim over clinical test data and the idea that data exclusivity can prevent the generic competitors from ‘free‐riding’ encounters some important problems: Neither legitimize excluding all others.     

Survey on Ethical Conduct Thresholds in Cardiologal Medical Practice in Argentina

The purpose of this study was to analyze the attitude of a group of cardiologists on the ethical conducts they would accept or adopt when encountered with different hypothetical situations of medical practice. Between August and September of 2011, 700 Argentine cardiologists were surveyed in situations which posed ethical dilemmas in the patient‐physician relationship, among colleagues or involving financial agreements with employers or the pharmaceutical industry. Ethical conflicts were evidenced in a series of inappropriate conducts such as differential fees, trips and meals sponsored by laboratories, splitting fees, overbilling, self‐referral, charging for patient referral, financial compensation for ordering medical procedures, and various situations derived from the relationship with employers. In general, financial compensation from the pharmaceutical industry was more accepted than the conflictive situations which directly involved patients, colleagues or employers. The rejection of these conducts, the physicians' deontological education and the improvement of financial and organizational conditions in medical practice will help to encourage better medical professionalism and avoid unseemly behaviors.     

Prerequisites for the pharmaceutical industry to develop and commercialise helminths and helminth-derived product therapy

During the past 10 years, immunologists, epidemiologists and parasitologists have made many new exciting discoveries in the field of helminth-mediated immune regulation. In addition, many animal experiments have shown that certain helminths or products derived from helminths can protect mice from developing allergic or autoimmune disease. Some clinical trials utilising Trichuris suis or Necator americanus for the treatment of allergic disorders and inflammatory bowel disease have been conducted. The outcomes of these trials suggest that they may be used to treat these disorders. However, to date no helminth therapy is routinely being applied to patients and no helminth-derived product therapy has been developed. In order to bring new drugs to the market and shoulder the enormous costs involved in developing such therapies, pharmaceutical companies need to be involved. However, currently the resources from the pharmaceutical industry devoted to this concept are relatively small and there are good reasons why the industry may have been reluctant to invest in developing these types of therapies. In this review article, the hurdles that must be overcome before the pharmaceutical industry might invest in these novel therapies are outlined.     

Factors influencing the inhibition of protein kinases

The protein kinase field is a very active research area in the pharmaceutical industry and many activities are ongoing to identify inhibitors of these proteins. The design of new chemical entities with improved pharmacological properties requires a deeper understanding of the factors that modulate inhibitor-kinase interactions. In this report, we studied the effect of two of these factors--the magnesium ion cofactor and the protein substrate--on inhibitors of the type I insulin-like growth factor receptor. Our results show that the concentration of magnesium ion influences the potency of adenosine triphosphate (ATP) competitive inhibitors, suggesting an explanation for the observation that such compounds retain their nanomolar potency in cells despite the presence of millimolar levels of ATP. We also showed that the peptidic substrate affects the potency of these inhibitors in a different manner, suggesting that the influence of this substrate on compound potency should be taken into consideration during drug discovery.     

Practical considerations for using functional uniform prior distributions for dose‐response estimation in clinical trials

Estimating nonlinear dose‐response relationships in the context of pharmaceutical clinical trials is often a challenging problem. The data in these trials are typically variable and sparse, making this a hard inference problem, despite sometimes seemingly large sample sizes. Maximum likelihood estimates often fail to exist in these situations, while for Bayesian methods, prior selection becomes a delicate issue when no carefully elicited prior is available, as the posterior distribution will often be sensitive to the priors chosen. This article provides guidance on the usage of functional uniform prior distributions in these situations. The essential idea of functional uniform priors is to employ a distribution that weights the functional shapes of the nonlinear regression function equally. By doing so one obtains a distribution that exhaustively and uniformly covers the underlying potential shapes of the nonlinear function. On the parameter scale these priors will often result in quite nonuniform prior distributions. This paper gives hints on how to implement these priors in practice and illustrates them in realistic trial examples in the context of Phase II dose‐response trials as well as Phase I first‐in‐human studies.     

Filmic encounters: Multispecies care and sacrifice on island Timor

This is a story about the ‘arts of noticing’ more‐than‐human noticing. In it I reflect on the ways in which my own practice of ethnographic filmmaking is itself an agent of multisensory participation. As artifice and artificial eye, there is something both liberating and sensuous about filmmaking practice. It heightens the performativity of participants and their embodied rituals and allows me to enter intimate spaces I would otherwise not encounter. In these encounters a deep multispecies noticing takes place, although in the first instance this is usually only by the camera. The intimacy enabled in these artificial but sensorial encounters can be both revealing and confronting, especially in cases of animal sacrifice. Re‐encountering footage filmed across years of research‐led endeavour, in this paper I explore the power of film to convey these multisensory and multispecies stories, as well as to evoke understanding and engage the multisensory memory of the filmmaker.     

Paradigms of expected failure

This study explores the outsourcing and offshoring of clinical trials and how they interconnect with the dynamics of drug development and regulation in the United States. I focus on the activities of United States-based contract research organizations, which make up a specialized global clinical trials industry focusing on the recruitment of human subjects and investigators. Tracking this industry’s activities in eastern Europe and Latin America, two clinical trial market ‘growth regions,’ I address the strategies of evidence-making that inform clinical trial offshoring. I also show how aspects of the clinical trial model—in which failures to predict safety outcomes or a paradigm of expected failure—are being exported along with the offshored trial. The clinical trials industry is a crucial, highly mobile, and profitable arm of the global pharmaceutical industry. Where state agencies furnish limited or no health care, drug developers claim that trial expansion and experiments have become social goods in themselves. But questions remain: How is drug value and research integrity maintained? And how do the results of clinical trials strengthen or undermine the delivery of affordable and effective interventions? As this essay shows, clinical trials are not only hypothesis-testing instruments; they are operative environments redistributing resources and occasioning tense medical and social fields. In highlighting the inefficiencies and uncertainties of global drug development, this study points to problems in the operational model of drug development and in systems of human protection. It also considers new forms of accountability at the nexus of private sector science and public health.     

Genetic relationships among traits related to reproduction and growth of Nelore females

The objective of the study presented here was to analyze the genetic relationships among heifer pregnancy (HP), age at first calving (AFC), stayability (STAY), average annual productivity of the cow, in kilograms of weaned calf per cow per year (PRODAM), postweaning weight gain (PWG), and hip height (HH) of Nelore females from 12 Brazilian herds. (Co)variance components were obtained by six-trait animal model using Gibbs sampling. The posterior mean of the heritability estimates were 0.37, 0.18, 0.19, 0.16, 0.21, and 0.37 for HP, AFC, STAY, PRODAM, PWG, and HH, respectively. In general, the genetic correlations were strong between traits related to reproduction, for example, −0.85 between HP and AFC, and 0.94 between STAY and PRODAM. Weak genetic correlations were obtained between reproductive and growth traits (absolute values ranging from 0.02 to 0.30). Although weak, the genetic correlations between PWG and reproductive traits were favorable, whereas the genetic correlations between HH and reproductive traits were close to zero and slightly unfavorable for HP, AFC, and STAY. An increase of HH is therefore expected to have little or no negative effect on the reproductive performance of females. The posterior mean of genetic correlation between PWG and HH was moderate (0.50). On the basis of the heritability, genetic correlation estimates, and time to obtain data, HP and PRODAM seems to show the best potential as selection criteria to improve the productive and reproductive performance of Nelore females. In principle, it is possible to select for increased PWG without compromising the reproduction of Nelore females. However, selection for PWG may result in an increase of female HH as a correlated response, a fact that could increase management costs in advanced generations of selection. In the light of the results, all traits studied here can be used as selection criteria and there is no strong evidence of genetic antagonism among traits related to reproduction and growth of Nelore females.