The ethics and economics of pharmaceutical pricing.

The cost of drugs is a major and rapidly rising component of health-care expenditures. We survey recent literature on the ethics and economics of skyrocketing pharmaceutical prices and find that advances in economic research have increased the sharpness and focus of the ethically based calls to increase access by modifying patent protection and reducing prices. In some cases, research supports ethical arguments for broader access. Other research suggests that efforts to broaden access result in unintended consequences for innovation and the medical needs of patients. Both ethicists and economists need to be more cognizant of the real clinical settings in which physicians practice medicine with real patients. Greater cross-disciplinary interaction among economists, ethicists, and physicians can help reduce the disjunction between innovation and access and improve access and patient care. This dialogue will impact private industry and may spur new multistakeholder paradigms for drug discovery, development, and pricing.

Consent for genetic research in the Framingham Heart Study.

Extensive efforts have been aimed at understanding the genetic underpinnings of complex diseases that affect humans. Numerous genome-wide association studies have assessed the association of genes with human disease, including the Framingham Heart Study (FHS), which genotyped 550,000 SNPs in 9,000 participants. The success of such efforts requires high rates of consent by participants, which is dependent on ethical oversight, communications, and trust between research participants and investigators. To study this we calculated percentages of participants who consented to collection of DNA and to various uses of their genetic information in two FHS cohorts between 2002 and 2009. The data included rates of consent for providing a DNA sample, creating an immortalized cell line, conducting research on various genetic conditions including those that might be considered sensitive, and for notifying participants of clinically significant genetic findings were above 95%. Only with regard to granting permission to share DNA or genetic findings with for-profit companies was the consent rate below 95%. We concluded that the FHS has maintained high rates of retention and consent for genetic research that has provided the scientific freedom to establish collaborations and address a broad range of research questions. We speculate that our high rates of consent have been achieved by establishing frequent and open communications with participants that highlight extensive oversight procedures. Our approach to maintaining high consent rates via ethical oversight of genetic research and communication with study participants is summarized in this report and should be of help to other studies engaged in similar types of research. Published 2010 Wiley-Liss, Inc.

Financial relationships between institutional review board members and industry.

BACKGROUND: Little is known about the nature, extent, and consequences of financial relationships between industry and institutional review board (IRB) members in academic institutions. We surveyed IRB members about such relationships. METHODS: We surveyed a random sample of 893 IRB members at 100 academic institutions (response rate, 67.2%). The questionnaire focused on the financial relationships that the members had with industry (e.g., employment, membership on boards, consulting, receipt of royalties, and paid speaking). RESULTS: We found that 36% of IRB members had had at least one relationship with industry in the past year. Of the respondents, 85.5% said they never thought that the relationships that another IRB member had with industry affected his or her IRB-related decisions in an inappropriate way, 11.9% said they thought this occurred rarely, 2.4% thought it occurred sometimes, and 0.2% thought it occurred often. Seventy-eight respondents (15.1%) reported that at least one protocol came before their IRB during the previous year that was sponsored either by a company with which they had a relationship or by a competitor of that company, both of which could be considered conflicts of interest. Of these 78 members (62 voting members and 16 nonvoting members), 57.7% reported that they always disclosed the relationship to an IRB official, 7.7% said they sometimes did, 11.5% said they rarely did, and 23.1% said they never did. Of the 62 voting members who reported conflicts, 64.5% reported that they never voted on the protocol, 4.8% said they rarely did, 11.3% said they sometimes did, and 19.4% said they always did. Most respondents reported that the views of IRB members who had experience working with industry were beneficial in reviewing industry-sponsored protocols. CONCLUSIONS: Relationships between IRB members and industry are common, and members sometimes participate in decisions about protocols sponsored by companies with which they have a financial relationship. Current regulations and policies should be examined to be sure that there is an appropriate way to handle conflicts of interest stemming from relationships with industry.

The Shared Ethical Responsibility of Medically and Non-medically Qualified Experts in Human Drug Development Teams.

The complexity of developing and applying increasingly sophisticated new medicinal products has led to the participation of many non-medically qualified scientists in multi-disciplinary non-clinical and clinical drug development teams world-wide. In this introductory paper to the "IFAPP International Ethics Framework for Pharmaceutical Physicians and Medicines Development Scientists" it is argued that all members of such multidisciplinary teams must share the scientific and ethical responsibilities since they all influence directly or indirectly both the outcome of the various phases of the medicines development projects and the safety of the research subjects involved. The participating medical practitioner retains the overriding responsibility and the final decision to stop a trial if the well-being of the research subjects is seriously endangered. All the team members should follow the main ethical principles governing human research, the respect for autonomy, justice, beneficence and non-maleficence. Nevertheless, the weighing of these principles might be different under various conditions according to the specialty of the members.

The synergy of the whole: building a global system for clinical trials to accelerate medicines development.

PURPOSE: The pharmaceutical industry, once highly respected, productive, and profitable, is in the throes of major change driven by many forces, including economics, science, regulation, and ethics. A variety of initiatives and partnerships have been launched to improve efficiency and productivity but without significant effect because they have failed to consider the process as a system. METHODS: Addressing the challenges facing this complex endeavor requires more than modifications of individual processes; it requires a fully integrated application of systems thinking and an understanding of the desired goals and complex interactions among essential components and stakeholders of the whole. A multistakeholder collaborative effort, led by the Alliance for Clinical Research Excellence and Safety (ACRES), a global nonprofit organization operating in the public interest, is now under way to build a shared global system for clinical research. Its systems approach focuses on the interconnection of stakeholders at critical points of interaction within 4 operational domains: site development and support, quality management, information technology, and safety. The ACRES initiatives, Site Accreditation and Standards, Product Safety Culture, Global Ethical Review and Regulatory Innovation, and Quality Assurance and Safety, focus on building and implementing systems solutions. Underpinning these initiatives is an open, shared, integrated technology (site and optics and quality informatics initiative). FINDINGS: We describe the rationale, challenges, progress, and successes of this effort to date and lessons learned. The complexity and fragmentation of the intensely proprietary ecosystem of drug development, challenging regulatory climate, and magnitude of the endeavor itself pose significant challenges, but the economic, social, and scientific rewards will more than justify the effort. IMPLICATIONS: An effective alliance model requires a willingness of multiple stakeholders to work together to build a shared system within a noncompetitive space that will have major benefits for all, including better access to medicines, better health, and more productive lives.

Corrigendum: Core competencies for pharmaceutical physicians and drug development scientists.

[This corrects the article on p. 105 in vol. 4, PMID: 23986704.].

Core competencies for pharmaceutical physicians and drug development scientists.

Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide.

Comment on "Multidimensional results reporting to participants in genomic studies: getting it right".

Bookman et al. write to correct the impression given in the Commentary by Kohane and Taylor that the recommendations of the National Heart, Lung, and Blood Institute (NHLBI) Working Group "Reporting Genetic Results in Research Studies" included advice to return genetic information to research subjects only in cases where there is a proven or preventative intervention for the identified disorder. In fact, the report does recommend that genetic information be returned to subjects when there is an intervention available, but it does not recommend against giving this kind of information to subjects if there is no available intervention.

Policies and management of conflicts of interest within medical research institutional review boards: results of a national study.

PURPOSE: To examine institutional review board (IRB) policies and practices with regard to conflicts of interest (COIs) among IRB members who review and approve research protocols and to assess IRB policies and procedures in light of federal policies and guidance. METHOD: An anonymous survey of IRB chairs serving the most research-intensive medical institutions in the United States was conducted in fall 2005. The survey collected information about the chairs, the IRBs, and the processes IRBs had in place to manage member relationships and COIs. RESULTS: Two hundred eleven out of 296 eligible chairs responded (71.7%). One third of IRBs in the nation's medical schools and major academic medical centers did not require voting members to disclose relationships with industry. In practice, IRB member industry relationships were disclosed to the entire IRB (75.9%), the IRB chair (62.1%), and/or a group or entity separate from the IRB but within the institution it serves (52.5%). One in five chairs of IRBs did not feel confident that their IRB's policies and procedures ensured appropriate disclosure of industry relationships in every case. Finally, one in four IRBs did not have written policies defining appropriate actions when IRB member COIs were identified. CONCLUSIONS: The relatively high proportion of IRBs without a requirement that voting members disclose industry relationships is inconsistent with current guidance, and likely results in lapses in awareness of when members with conflicts vote on protocols. There was no clear consensus on where oversight responsibility for member-industry relationships should lie.

Opinions of IRB Members and Chairs Regarding Investigators' Relationships with Industry.

THE EFFECTS OF CONFLICTS OF INTEREST on the conduct of human research have been roundly debated, but less attention has been paid to the role of Institutional Review Boards (IRBs) in their identification and management. Government and private policy recommendations disagree about IRBs' responsibility in this area. A survey focusing on respondents' attitudes and behaviors regarding consideration of investigator and institutional financial relationships with industry when reviewing research protocols was mailed to a random sample of 893 IRB members and 316 IRB chairs at 115 academic institutions (response rates of 67% and 72%, respectively). More than half of IRB members and chairs felt that industry relationships posed a moderate or big problem for research integrity nationally, and about one-third thought such relationships were a problem at their own institution. Approximately two-thirds felt that investigator-industry relationships should be considered when reviewing protocols regardless of whether they are deemed to be conflicts of interest. While more than 90% of IRB members and chairs believed that investigators' relationships should be disclosed to research participants, 61% of members and chairs reported that these relationships were not always disclosed to participants. While more than 80% believed that institutional relationships should be disclosed to research participants, only 39% of members and chairs said this happened all the time. Some beliefs of IRB members and chairs are at odds with recommendations to limit the role of IRBs in the management of potential investigator conflicts. Lack of unambiguous guidelines has led to inconsistent practices among IRBs.