Current issues in clinical research and the development of new pharmaceuticals

As a normal part of the drug development process, U.S. pharmaceutical companies conduct many thousands of clinical trials each year. Only after a reasonable assurance of safety is made can the drug be given to patients who have the underlying medical condition that the drug is designed to treat. Patient welfare is assured by adhering to the Food and Drug Administration's interpretation of the “common rule”; if the data will be used to support a licensing application. 21 CFR Part 50 sets forth the regulations along with the principles of informed consent and the use of institutional review boards (IRBs) that assure patients’ rights are protected. Any potential conflict of interest on the part of a clinical investigator must be reported to the FDA. Pharmaceutical companies extensively monitor ongoing clinical trials for compliance with appropriate regulations. The recent revision of the Declaration of Helsinki governing placebo‐controlled clinical trials may adversely impact drug development     

Building a More Connected DSMB: Better Integrating Ethics Review and Safety Monitoring

Data and Safety Monitoring Boards (DSMBs) have become an increasingly common feature of clinical trial oversight, yet a paucity of legal or ethical frameworks govern these Boards’ composition or operation, or their relationship with other actors with monitoring responsibilities. This paper argues that prevailing structural gaps are impeding harmonized systems for monitoring the ongoing ethical acceptability of clinical trials. Particular tensions stem from DSMBs’ sweeping discretion in deciding whether and when to recommend that a trial should be terminated or amended based on safety and efficacy information. This discretion becomes especially challenging in light of DSMBs’ monopoly over emerging trial data, which prevents Institutional Review Boards, sponsors, and investigators from participating in certain pivotal and ethically charged decisions. To address these disconnects, I advocate for strengthened pre-trial and post-trial communication in addition to innovative strategies to support DSMB decision making through the life of a trial.     

Reforming the Oversight of Multi-Site Clinical Research: A Review of Two Possible Solutions

The current system for the ethical oversight of clinical research suffers from structural, procedural, and performance assessment problems. Initially conceived primarily to handle local investigator-initiated single-site studies, the system of institutionally-based committee review has become progressively more inefficient given the increased prevalence of commercially or federally sponsored multi-center trials. To date, proposed solutions do not adequately address these problems.

Beginning with a review of these structural, procedural, and performance assessment problems, this article will then consider two proposals for addressing these deficiencies: (a) regional ethics organizations; and (b) IRBNet?, a newly developed web-based program for cooperative IRB review. The strengths and weaknesses of these two approaches will be evaluated in light of recent experience with centralized review. The proposal to establish a system of regional ethics organizations presents a comprehensive approach to many of the problems faced by the current system. However, IRBNet? offers an immediate and feasible solution to many of the problems faced by the review of multi-site clinical studies.     

Minimal Risk in Pediatric Research: A Philosophical Review and Reconsideration

Despite more than thirty years of debate, disagreement persists among research ethicists about the most appropriate way to interpret the U.S. regulations on pediatric research, specifically the categories of “minimal risk” and a “minor increase over minimal risk.” Focusing primarily on the definition of “minimal risk,” we argue in this article that the continued debate about the pediatric risk categories is at least partly because their conceptual status is seldom considered directly. Once this is done, it becomes clear that the most popular strategy for interpreting “minimal risk”—defining it as a specific set of risks—is indefensible and, from a pragmatic perspective, unlikely to resolve disagreement. Primarily this is because judgments about minimal risk are both normative and heavily intuitive in nature and thus cannot easily be captured by reductions to a given set of risks. We suggest instead that a more defensible approach to evaluating risk should incorporate room for reflection and deliberation. This dispositional, deliberative framework can nonetheless accommodate a number of intellectual resources for reducing reliance on sheer intuition and improving the quality of risk evaluations.     

The Canadian Agency for the Oversight of Research Involving Humans: A Reform Proposal

In this paper, I propose the creation of a Canadian agency for the oversight of research involving humans. I describe first a series of significant problems with Canada’s current system of oversight. I then argue for the creation of a national-level agency, covering all research involving humans, with three branches (policy and standards, education, and compliance). Of particular note, the proposed compliance branch consists of a number of independent national and regional Research Ethics Boards (i.e., REBs no longer reside within institutions). There is also an Audit Committee and a Non-compliance Committee (with supporting staff of auditors and compliance officers) to ensure compliance with the policies and standards set by the Policy and Standards Branch. Finally, I answer a series of “frequently asked questions” about the proposed agency design such as “What about ‘local context’?” and “Why not have a system of accreditation of institutional REBs instead?” In sum, radical reform is needed and, in this paper, I present a proposal for such reform.     

Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network

PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.     

National Scientific Misconduct Policies in Argentina: Two Definitions of Research Misconduct

ABSTRACT

In “An International Study of Research Misconduct Policies”, Resnik et al. count Argentina in the list of countries without national research misconduct policies. In this paper, we clarify that Argentina has national policies of research misconduct and present the research misconduct definitions of two official science organisms: the National Scientific and Technical Research Council (CONICET) and the Ethics Committee of the Argentine Ministry of Science (MINCyT).     

The Therapeutic Misconception: A Threat to Valid Parental Consent for Pediatric Neuroimaging Research

Neuroimaging research has brought major advances to child health and well-being. However, because of the vulnerabilities associated with neurological and developmental conditions, the parental need for hope, and the expectation of parents that new medical advances can benefit their child, pediatric neuroimaging research presents significant challenges to the general problem of consent in the context of research involving children. A particular challenge in this domain is created by the presence of therapeutic misconception on the part of parents and other key research stakeholders. This article reviews the concept of therapeutic misconception and its role in pediatric neuroimaging research. It argues that this misconception can compromise consent given by parents for the involvement of their children in research as healthy controls or as persons with neurological and developmental conditions. The article further contends that therapeutic misconception can undermine the research ethics review process for proposed and ongoing neuroimaging studies. Against this backdrop, the article concludes with recommendations for mitigating the effects of therapeutic misconception in pediatric neuroimaging research.     

The role of research in drug policy in Hong Kong: highlighting life satisfaction from two longitudinal studies of drug abusers

ABSTRACT

This paper examines the role of research in the development of drug policy in Hong Kong. The upsurge of the prevalence of psychoactive drug abuse in young people since the mid-1990s had brought about a great demand for medical and social science research on psychoactive drugs and users. Among a large number of Beat Drugs Fund-funded projects, two longitudinal studies, conducted between 2000 and 2002 and between 2009 and 2011, respectively, were used to illustrate the possible contributions of research findings to treatment and rehabilitation services. The most salient finding present in both studies was the significant and negative relationship between life satisfaction and continuation of drug use. The finding suggested that subjective well-being should be incorporated into treatment programmes, and there is a need to provide post-treatment services to young rehabilitated psychoactive drug abusers in the form of life planning programmes and organisation of sustainable social activities in the community.     

'Text-work' in Research Ethics Review: The significance of documents in and beyond committee meetings

ABSTRACT

This article analyzes how a formal text (the Ethics Review Form) available at National Health Service Research Ethics Committees (NHSRECs) in the United Kingdom was used in meetings. Derived from the work of Dorothy Smith on incorporating texts into institutional ethnography (IE), it proposes the concept of “text work” as a way into understanding more about decision-making in ethics review and describes the extent to which this formal text shaped and influenced review work. The research study used observations of committee meetings, field-notes and interviews to produce an ethnographic mapping of Research Ethics Committees’ (RECs) work. This article draws on one aspect of the research which was the process of isolating a particular, ubiquitous text and analyzing how it worked and was worked on in the meetings. The analysis contributes to contemporary discussion offering an alternative to ongoing debates about idealized ways of conducting ethics review. Finally, some tentative suggestions are made about improving training, based on and starting from the work which reviewers undertake.     

Grave fraudulence in medical device research: a narrative review of the PIN seeding study for the Pinnacle hip system

In 2001, DePuy, a wholly-owned subsidiary of Johnson & Johnson (J&J/DePuy), initiated a seeding study called the “Multi-center, Prospective, Clinical Evaluation of Pinnacle Acetabular Implants in Total Hip Arthroplasty” (PIN Study). J&J/DePuy designed this study to develop new business opportunities during the launch of their Pinnacle Hip System (PHS) and generate survivorship data for marketing. This article, the first review of a seeding trial for a medical device, examines internal company documents relating to the PIN Study; the analysis herein focuses on the integrity of J&J/DePuy’s research practices in conception, implementation, and analysis. J&J/DePuy violated the study protocol and manipulated data; consented participants in violation of standards protecting human subjects; and did not secure Institutional Review Board approval for all study sites. J&J/DePuy used PIN Study results as the “fundamental selling point” for the PHS. Medical device seeding trials are distinct from previously-documented pharmaceutical seeding trials because companies can profit directly from device sales and because these studies may be the first clinical evaluation of the device (as was the case for the PIN Study). Seeding trials are malleable marketing projects, not rigorous scientific studies. Regulatory bodies, physicians, and others should be vigilant for persuasive marketing accounts disguised as science.     

Protecting the Public's Health in An Era of Bioterrorism: The Model State Emergency Health Powers Act

During the fall of 2001, public health law scholars at the Center for Law and the Public's Health at Georgetown and Johns Hopkins Universities were asked by the Centers for Disease Control and Prevention (CDC) and a series of national partners to develop the Model State Emergency Health Powers Act (MSEHPA). The MSEHPA provides a series of modern powers for states to consider in responding to catastrophic public health emergencies, including bioterrorism events. Since December 2001, provisions based on the MSEHPA have been introduced in nearly 40 states and passed in 20. Underlying the development of the act is a long-standing debate between legal and ethical scholars and law- and policymakers as to the appropriate ways to balance individual and communal rights. The drafting challenge was to create a comprehensive model law that provides adequate powers to protect the public's health while also respecting individual and group rights. The MSEHPA empowers public health agents with broad authority and simultaneously limits the exercise of power in time, duration, and scope to accomplish communal goals of abating serious public health threats. Coercive public health powers, particularly isolation and quarantine, are exercised on a temporary basis, only so long as are reasonably necessary and only among persons who justifiably may pose a risk to others because of their contagious conditions. Individual rights to contest the coercive use of public health powers, even during an emergency, are secured.     

Informed consent comprehension among vulnerable populations in Ecuador: video-delivered vs. in-person standard method

The informed consent comprehension process is key to engaging potential research subject participation. The aim of this study is to compare informed consent comprehension between two methods: standard and video-delivered. We compared the in-person and video-delivered informed consent process in the Familias Unidas intervention. We evaluated comprehension using a 7-item true/false questionnaire. There were a total of 152 participants in the control group and 87 in the experimental. General characteristics were similar between both groups (p > 0.05). First-attempt informed consent comprehension was higher in the intervention group but was not statistically significant (80% and 78% respectively p = 0.44). A video-delivered informed consent process did not differ from the standard method of informed consent in a low educational and socioeconomic environment.     

Including the Socially Excluded: The Impact of Government Policy on Vulnerable Families and Children in Need

This paper is based on a literature review undertaken for theOffice of the Deputy Prime Minister in 2004 (Buchanan et al., 2004)on the impact of government policy in England and Wales forchildren aged from birth to thirteen at high risk of socialexclusion as recorded up until May 2004. It describes the conceptof ‘social exclusion’; its meaning for children;the aims of government policy; the specific impact of governmentpolicy on vulnerable families and children in need (includingchildren needing child protection and all ‘looked after’children) as defined by the 1989 Children Act. The paper demonstratesthat although progress has been made, there are still majorareas of concern. The more discursive parts at the end of thepaper reflect the views of the author and later thinking, andwere not part of the original submission to the Social ExclusionUnit.     

The Cycle of Bias in Health Research: A Framework and Toolbox for Critical Appraisal Training

Recognizing bias in health research is crucial for evidence-based decision making. We worked with eight community groups to develop materials for nine modular, individualized critical appraisal workshops we conducted with 102 consumers (four workshops), 43 healthcare providers (three workshops), and 33 journalists (two workshops) in California. We presented workshops using a “cycle of bias” framework, and developed a toolbox of presentations, problem-based small group sessions, and skill-building materials to improve participants' ability to evaluate research for financial and other conflicts of interest, bias, validity, and applicability. Participant feedback indicated that the adaptability of the toolbox and our focus on bias were critical elements in the success of our workshops.     

The housing fulcrum: Balancing economic and social factors in housing research and policy

Abstract

We discuss the pivotal role that housing plays for both social and economic outcomes. All people need to be housed, and housing circumstances help determine social outcomes, especially for vulnerable groups. We outline an analytical framework that treats housing as a dynamic system, incorporating the life‐cycles of both individuals/households and houses. Each is long‐lived; decisions impact on housing for decades. This approach is relevant to the development of housing research and housing policy. We illustrate the issues with reference to the relationship between rental yields and measures of deprivation across New Zealand. The surprising nature of this relationship has consequences regarding potential poverty traps and wealth disparities. While highlighting an important housing market issue, any policy response to this issue is complicated by the need to take account of the life‐cycles of both individuals and of houses, and by the long‐lasting impacts of decisions.     

A framework for comparing social protection in developing and developed countries: The example of child benefits

Abstract   The article outlines a conceptual and theoretical framework for improved comparative analysis of publicly provided social protection in developing countries, drawing on the research tradition of the study of longstanding welfare democracies. An important element of the proposed institutional approach is the establishment of comparable qualitative and quantitative indicators for social protection. The empirical example of child benefits indicates that differences between developed and developing countries should not be exaggerated, and that the prevalence of child benefits in sub-Saharan African and Latin American countries today resembles the inter-war period (1919-1938) situation in developed regions.     

Alternative care options and policy choices to support orphans: The case of Mozambique in the context of the SADC

Contextualizing the situation of orphans within the Southern African region and drawing on quantitative and qualitative field research, this article analyses care options and social protection policy for orphans in Mozambique, with its focus placed on children in orphan support centres. Seeking to offer new insights and greater understanding of the experiences of children in care and of the social protection available to them, the research highlights that orphaned children living in informal foster care arrangements are more likely to experience abuse, neglect and maltreatment than those living in non‐governmental care organizations. The research emphasizes the need for a more careful selection of foster families in which children are placed. Recommendations include the need to focus on capacity building and institutional reforms that provide social protection policies for orphaned children as part of an overall social protection floor. The monitoring and evaluation of organizations providing care to orphaned children is deemed a priority.