International stem cell collaboration: how disparate policies between the United States and the United Kingdom impact research

As the scientific community globalizes, it is increasingly important to understand the effects of international collaboration on the quality and quantity of research produced. While it is generally assumed that international collaboration enhances the quality of research, this phenomenon is not well examined. Stem cell research is unique in that it is both politically charged and a research area that often generates international collaborations, making it an ideal case through which to examine international collaborations. Furthermore, with promising medical applications, the research area is dynamic and responsive to a globalizing science environment. Thus, studying international collaborations in stem cell research elucidates the role of existing international networks in promoting quality research, as well as the effects that disparate national policies might have on research. This study examined the impact of collaboration on publication significance in the United States and the United Kingdom, world leaders in stem cell research with disparate policies. We reviewed publications by US and UK authors from 2008, along with their citation rates and the political factors that may have contributed to the number of international collaborations. The data demonstrated that international collaborations significantly increased an article's impact for UK and US investigators. While this applied to UK authors whether they were corresponding or secondary, this effect was most significant for US authors who were corresponding authors. While the UK exhibited a higher proportion of international publications than the US, this difference was consistent with overall trends in international scientific collaboration. The findings suggested that national stem cell policy differences and regulatory mechanisms driving international stem cell research in the US and UK did not affect the frequency of international collaborations, or even the countries with which the US and UK most often collaborated. Geographical and traditional collaborative relationships were the predominate considerations in establishing international collaborations.     

Straight talk with... Mark Sculpher

By 2014, the UK will be changing the way it regulates the price it pays for medicines. Currently the country's National Health Service (NHS) uses the Pharmaceutical Price Regulation Scheme (PPRS), which controls the maximum profit a drug manufacturer can make on the basis of capital investments the manufacturer has made. A review of this system, carried out by the UK Office of Fair Trading in 2007, recommended that, instead, medicines should be priced according to the therapeutic benefits they offer to patients-an idea known as value-based pricing (VBP) that has similarities to systems already used in smaller countries such as Australia and Canada. This pricing scheme has been embraced by the UK government, and negotiations on how the system will work are due to begin this month. A British switch to VBP could have ripple effects throughout the global pharmaceutical industry. Even though the UK's share of the world drug market is relatively small-just 3%-drug prices in the country are important because a quarter of national governments reference British values to determine their own sticker prices. One of the most influential thinkers on the UK's proposed system is health economist Mark Sculpher, director of the Programme on Economic Evaluation and Health Technology Assessment at the University of York. As a regular advisor to the UK National Institute for Health and Clinical Excellence (NICE) and former chair of a task force on methods guidance for economic evaluation at the agency, Sculpher has had an instrumental role in guiding value-based decision-making in the country's healthcare system. Kate Ravilious met with Sculpher at his office in York to discuss the value of VBP.     

Clinical effectiveness and cost effectiveness of zanamivir (Relenza): translating the evidence into clinical practice, a National Institute for Clinical Excellence view.

The UK National Institute for Clinical Excellence (NICE) is charged with the duty of providing informed guidance on clinical practice (clinical effectiveness and cost effectiveness) to patients and health professionals. The Appraisal Committee through its process of review of evidence advises NICE on the clinical effectiveness and cost effectiveness of new and existing technologies and their appropriate use within the National Health Service in England and Wales. The appraisal process takes into account both published and unpublished evidence as well as input from professional and patient and carer groups when coming to its decisions. The appraisal of a new technology often has to bridge the gap between the evidence required for licensing purposes and that needed to provide pragmatic advice to practising clinicians. The appraisal of zanamivir (Relenza) is an excellent working example of this difficult and important process.     

The business of exploiting induced pluripotent stem cells

Induced pluripotent stem cells (iPS cells) can be exploited for both research and clinical applications. The first part of this review seeks to provide an understanding of the financial drivers and key elements of a successful business strategy that underpin a company focused on developing iPS-related products and services targeted at the research market. The latter part of the review highlights some of the reasons as to why the reprogramming of somatic cells is currently being used to develop cell-based models to screen for small molecules with drug-like properties rather than to develop cell-based regenerative medicines per se. The latter may be used to repair or replace a patient's damaged cells and thereby have the potential to 'cure' a disease and, in doing so, prevent or delay the onset of associated medical conditions. However, the cost of an expensive regenerative medicine and time to accrue any benefit linked to a decrease in co-morbidity expenditure may not outweigh the benefit for a healthcare community that has finite resources. The implications of this are discussed together with evidence that the UK National Institute for Health and Clinical Excellence (NICE) and the National Health Service (NHS) have established a precedent for a cost-sharing strategy with the pharmaceutical industry.     

PITO: Mission accomplished?

The UK’s Police Information Technology Organisation (PITO) sponsored a fact finding mission to the USA at the end of 2001. It was designed to understand the latest thinking in the US law and enforcement sector, to build new relationships and to promote the UK’s biometrics industry. The following article describes the mission and its outcome, and highlights the very different business environment that exists in the US compared with the UK.     

Commentary: "health has become secondary to a sexually attractive body"

This article focuses on the prevalence of cesarean section among upper class women for aesthetic purposes. In Latin America, the national cesarean section rate has risen to 40%, while in the early 1980s the rate was 75% in Brazil. In a survey conducted in the UK, 31% of women obstetricians would prefer to have cesarean section without any medical indication. This could perhaps be due to the obsession of maintaining a sexually appealing body. Health has then become secondary to the production of a sexually attractive body. The role of the medical profession lacks the definitive evidence on the issues regarding concerns of women and choices in childbirth particularly in some countries. The author suggests that the medical community and society should allow the women the choice between major surgery and childbirth.     

Facilitating the Recruitment of Minority Ethnic People into Research: Qualitative Case Study of South Asians and Asthma

Background

There is international interest in enhancing recruitment of minority ethnic people into research, particularly in disease areas with substantial ethnic inequalities. A recent systematic review and meta-analysis found that UK South Asians are at three times increased risk of hospitalisation for asthma when compared to white Europeans. US asthma trials are far more likely to report enrolling minority ethnic people into studies than those conducted in Europe. We investigated approaches to bolster recruitment of South Asians into UK asthma studies through qualitative research with US and UK researchers, and UK community leaders.

Methods and Findings

Interviews were conducted with 36 researchers (19 UK and 17 US) from diverse disciplinary backgrounds and ten community leaders from a range of ethnic, religious, and linguistic backgrounds, followed by self-completion questionnaires. Interviews were digitally recorded, translated where necessary, and transcribed. The Framework approach was used for analysis. Barriers to ethnic minority participation revolved around five key themes: (i) researchers'' own attitudes, which ranged from empathy to antipathy to (in a minority of cases) misgivings about the scientific importance of the question under study; (ii) stereotypes and prejudices about the difficulties in engaging with minority ethnic populations; (iii) the logistical challenges posed by language, cultural differences, and research costs set against the need to demonstrate value for money; (iv) the unique contexts of the two countries; and (v) poorly developed understanding amongst some minority ethnic leaders of what research entails and aims to achieve. US researchers were considerably more positive than their UK counterparts about the importance and logistics of including ethnic minorities, which appeared to a large extent to reflect the longer-term impact of the National Institutes of Health''s requirement to include minority ethnic people.

Conclusions

Most researchers and community leaders view the broadening of participation in research as important and are reasonably optimistic about the feasibility of recruiting South Asians into asthma studies provided that the barriers can be overcome. Suggested strategies for improving recruitment in the UK included a considerably improved support structure to provide academics with essential contextual information (e.g., languages of particular importance and contact with local gatekeepers), and the need to ensure that care is taken to engage with the minority ethnic communities in ways that are both culturally appropriate and sustainable; ensuring reciprocal benefits was seen as one key way of avoiding gatekeeper fatigue. Although voluntary measures to encourage researchers may have some impact, greater impact might be achieved if UK funding bodies followed the lead of the US National Institutes of Health requiring recruitment of ethnic minorities. Such a move is, however, likely in the short- to medium-term, to prove unpopular with many UK academics because of the added “hassle” factor in engaging with more diverse populations than many have hitherto been accustomed to. Please see later in the article for the Editors'' Summary     

Challenges and opportunities for enhancing biotechnology and technology transfer in developing countries

Biotechnological innovation is gaining increased recognition as an important tool for improving global health. The challenge, however, lies in defining the role of technology transfer to develop therapies for diseases prevalent in developing countries. During the past decade, a large disparity emerged between the developed and developing world in accessing affordable medicines because of the pharmaceutical industry's focus on health areas bearing greatest profits. Discussed herein are several mechanisms that provide partial solutions to this challenge. The Office of Technology Transfer of the US National Institutes of Health has increased its technology licensing pertaining to neglected diseases to partners in developing regions. Establishing partnerships through the transfer of technologies and assisting indigenous institutions build R and D capacity may positively impact policies on protection of intellectual property rights and increase multinational company investments in lesser-developed countries. This will most probably result in the development of more accessible therapies for those in need.     

US IRBs confronting research in the developing world

Increasingly, US‐sponsored research is carried out in developing countries, but how US Institutional Review Boards (IRBs) approach the challenges they then face is unclear. METHODS: I conducted in‐depth interviews of about 2 hours each, with 46 IRB chairs, directors, administrators and members. I contacted the leadership of 60 IRBs in the United States (US) (every fourth one in the list of the top 240 institutions by National Institutes of Health (NIH) funding), and interviewed IRB leaders from 34 (55%). RESULTS: US IRBs face ethical and logistical challenges in interpreting and applying principles and regulations in developing countries, given economic and health disparities, and limited contextual knowledge. These IRBs perceive wide variations in developing world IRBs/RECs' quality, resources and training; and health systems in some countries may have long‐standing practices of corruption. These US IRBs often know little of local contexts, regulations and standards of care, and struggle with understandings of other cultures' differing views of autonomy, and risks and benefits of daily life. US IRBs thus face difficult decisions, including how to interpret principles, how much to pay subjects and how much sustainability to require from researchers. IRB responses and solutions include trying to maintain higher standards for developing world research, obtain cultural expertise, build IRB infrastructure abroad, communicate with foreign IRBs, and ‘negotiate’ for maximum benefits for participants and fearing ‘worst‐case scenarios’. CONCLUSIONS: US and foreign IRBs confront a series of tensions and dilemmas in reviewing developing world research. These data have important implications for increased education of IRBs/RECs and researchers in the US and abroad, and for research and practice.     

6-Hydroxydopamine infusions into the structures of mesolimbic dopaminergic system alter the memory enhancing effect of CK-8US and caerulein in rats

The influence of bilateral destruction of dopaminergic endings in the anterior and in the posterior part of nucleus accumbens (NAS) and in the nucleus septi lateralis (NSL), by 6-hydroxydopamine (6-OHDA) infusions, on the facilitatory effect of cholecystokinin-unsulfated octapeptide (CCK-8US) and caerulein (CER) on memory motivated affectively was investigated in male Wistar rats. CCK-8US and CER were given s.c. at the doses of 10 microg/kg and 0.5 microg/kg respectively, immediately after a single learning trial in a passive avoidance situation, ten days after bilateral 6-OHDA lesions (desipramine pre-treatment; 25 mg/kg, i.p.) of these structures. Bilateral 6-OHDA lesions to the anterior and to the posterior part of NAS totally abolished and significantly attenuated, respective, the facilitatory effect of CCK-8US and CER on retention of a passive avoidance behaviour evaluated 24 h later, while bilateral lesions to NSL did not have any influence on it. Moreover, neither, destruction of dopaminergic endings in lesioned structures, nor application of CCK-8US and CER changed the spontaneous psychomotor activity of rats estimated in an "open field" test. These results may indicate that dopaminergic projection to the anterior part of NAS is mainly responsible for the facilitatory effect of CCK-8US and CER on memory motivated affectively.     

Biological weapons, genetics, and social analysis: emerging responses, emerging issues--II

Recent terrorist attacks in the United States have generated significant attention in many countries to the threats posed by biological weapons. In response to these events and the specter of future attacks, bioscientists and professional organizations have begun or intensified asking questions about the possible malign applications of their research. Part II of this two-part article examines the emerging responses initiated by biomedical organizations and spokespersons in the US and the UK. In doing so it considers how scientific and medical research communities are defining and policing notions of professionalism, responsibility and accountability in the responses made. Through an examination of these issues, suggested lines for future social analysis are offered.     

Doing something about tuberculosis

The phenomenal success public health officials enjoyed in controlling tuberculosis (TB) in developed countries has not been mirrored in developing countries, where TB still accounts for 25% of preventable deaths in adults. The fact that there are 8 million new cases each year (95% in developing countries) and 3 million deaths (98% in developing countries) led to the 1993 declaration by the World Health Organization (WHO) that TB poses a global emergency. Because TB is predominantly a disease of impoverished people, indifference has led to the fallacious and naive view that eradication of TB simply requires socioeconomic development. In response to this indifference, the WHO is promoting a "Stop TB--Use DOTS" campaign. DOTS, a strategy based on directly observed therapy, also requires government commitment, a regular supply of drugs, effective diagnoses, and an audit of the efficacy of the strategy. While the treatment of TB is among the most cost-effective of all medical interventions in terms of years of healthy life saved, the DOTS campaign requires a considerable dedication of funds. Renewed interest in TB is leading the US and the UK to increase support for control programs. In addition, a new UK-based charity, "TB Alert," hopes to play a major role in advocating for political commitment to and funding for TB control.     

Biological weapons,genetics, and social analysis: emerging responses,emerging issues—II

Recent terrorist attacks in the United States have generated significant attention in many countries to the threats posed by biological weapons. In response to these events and the specter of future attacks, bioscientists and professional organizations have begun or intensified asking questions about the possible malign applications of their research. Part II of this two-part article examines the emerging responses initiated by biomedical organizations and spokespersons in the US and the UK. In doing so it considers how scientific and medical research communities are defining and policing notions of professionalism, responsibility and accountability in the responses made. Through an examination of these issues, suggested lines for future social analysis are offered.     

International Migration of Doctors,and Its Impact on Availability of Psychiatrists in Low and Middle Income Countries

Background

Migration of health professionals from low and middle income countries to rich countries is a large scale and long-standing phenomenon, which is detrimental to the health systems in the donor countries. We sought to explore the extent of psychiatric migration.

Methods

In our study, we use the respective professional databases in each country to establish the numbers of psychiatrists currently registered in the UK, US, New Zealand, and Australia who originate from other countries. We also estimate the impact of this migration on the psychiatrist population ratios in the donor countries.

Findings

We document large numbers of psychiatrists currently registered in the UK, US, New Zealand and Australia originating from India (4687 psychiatrists), Pakistan (1158), Bangladesh (149) , Nigeria (384) , Egypt (484), Sri Lanka (142), Philippines (1593). For some countries of origin, the numbers of psychiatrists currently registered within high-income countries'' professional databases are very small (e.g., 5 psychiatrists of Tanzanian origin registered in the 4 high-income countries we studied), but this number is very significant compared to the 15 psychiatrists currently registered in Tanzania). Without such emigration, many countries would have more than double the number of psychiatrists per 100, 000 population (e.g. Bangladesh, Myanmar, Afghanistan, Egypt, Syria, Lebanon); and some countries would have had five to eight times more psychiatrists per 100,000 (e.g. Philippines, Pakistan, Sri Lanka, Liberia, Nigeria and Zambia).

Conclusions

Large numbers of psychiatrists originating from key low and middle income countries are currently registered in the UK, US, New Zealand and Australia, with concomitant impact on the psychiatrist/population ratio n the originating countries. We suggest that creative international policy approaches are needed to ensure the individual migration rights of health professionals do not compromise societal population rights to health, and that there are public and fair agreements between countries within an internationally agreed framework.     

Managing Conflicts of Interest in the UK National Institute for Health and Care Excellence (NICE) Clinical Guidelines Programme: Qualitative Study

Background

There is international concern that conflicts of interest (COI) may bias clinical guideline development and render it untrustworthy. Guideline COI policies exist with the aim of reducing this bias but it is not known how such policies are interpreted and used by guideline producing organisations. This study sought to determine how conflicts of interest (COIs) are disclosed and managed by a national clinical guideline developer (NICE: the UK National Institute for Health and Care Excellence).

Methods

Qualitative study using semi-structured telephone interviews with 14 key informants: 8 senior staff of NICE’s guideline development centres and 6 chairs of guideline development groups (GDGs). We conducted a thematic analysis.

Results

Participants regard the NICE COI policy as comprehensive leading to transparent and independent guidance. The application of the NICE COI policy is, however, not straightforward and clarity could be improved. Disclosure of COI relies on self reporting and guideline developers have to take “on trust” the information they receive, certain types of COI (non-financial) are difficult to categorise and manage and disclosed COI can impact on the ability to recruit clinical experts to GDGs. Participants considered it both disruptive and stressful to exclude members from GDG meetings when required by the COI policy. Nonetheless the impact of this disruption can be minimised with good group chairing skills.

Conclusions

We consider that the successful implementation of a COI policy in clinical guideline development requires clear policies and procedures, appropriate training of GDG chairs and an evaluation of how the policy is used in practice.     

<Emphasis Type="Bold">Intersex Activists in Israel: Their Achievements and the Obstacles They Face</Emphasis>

This article focuses on the dynamic between the medical policy on intersex bodies and intersex activists in Israel. Recently, in many countries changes have taken place in medical guidelines regarding intersex patients and laws that regulate medical practices and prohibit irreversible surgeries for intersex babies for cosmetic reasons and without the patient’s consent. In Israel, intersex activists are limited by several factors. On the one hand, they are influenced by the achievements of intersex activism around the world but on the other, the pathologizing medical discourse and socio-medical practices, which include early diagnosis, early irreversible surgeries, and secrecy surrounding intersexed bodies, present obstacles to achieving bodily autonomy for intersex individuals and social recognition of different sex development. Nevertheless, intersex activists are attempting to find different social and media spaces in which to achieve public acknowledgement and future bodily autonomy for intersexed people and seeking medical professionals’ cooperation. Recently, the Israeli Ministry of Health published a new circular for intersex/DSD patients, and while it does not clearly forbid irreversible surgeries, it provides information about the complexities of intersex people and their experience.     

Evaluation of the impact of a Herd Health and Production Management programme in organic dairy cattle farms: a process evaluation approach

Animal health planning activities are not always providing a satisfactory positive impact on herd health and welfare. Moreover, evaluating the impact of advisory programmes is complex due to multiple interacting elements that influence its outcome. Therefore, measuring solely health outcomes is not sufficient: the whole process of the implementation and use of such programmes should be evaluated. In order to evaluate the impact of an intervention with a Herd Health and Production Management (HHPM) programme a process evaluation framework was designed and used. The intervention involved 20 organic dairy cattle farmers and their advisors, in both France and Sweden. In both countries 20 organic dairy farms were selected as control herds. The evaluation of the HHPM programme was based on: (a) the compliance to the programme; (b) the programme’s functions influencing herd health management practices and stimulating dialogue between farmers and advisors; (c) its effectiveness in terms of improving herd health compared with control farms. Complete compliance to the programme was fulfilled by 21 out of 40 farmers–advisors. Results from a questionnaire showed that the programme functioned as intended (e.g. by allowing early identification of herd health problems), stimulated change in farmers’ herd health management practices and farmer–advisor dialogue. Even though the majority of the users perceived that the programme contributed to herd health improvements, no significant differences in health outcomes were found when compared with control farms 12 months after the start of the intervention. The programme allowed creating an environment promoting the exchange of information between farmers and advisors, necessary to define pertinent advice in a farm-specific situation. Future research should aim at improving methods for the evaluation of the effect of advisory programmes, by identifying early indicators for effective advice and developing methods to evaluate the quality of advisory situations without interfering with them.     

Designing research funding schemes to promote global health equity: An exploration of current practice in health systems research

International research is an essential means of reducing health disparities between and within countries and should do so as a matter of global justice. Research funders from high‐income countries have an obligation of justice to support health research in low and middle‐income countries (LMICs) that furthers such objectives. This paper investigates how their current funding schemes are designed to incentivise health systems research in LMICs that promotes health equity. Semi‐structured in‐depth interviews were performed with 16 grants officers working for 11 funders and organisations that support health systems research: the Alliance for Health Policy and Systems Research, Comic Relief, Doris Duke Foundation, European Commission, International Development Research Centre, Norwegian Agency for Development Cooperation, Research Council of Norway, Rockefeller Foundation, UK Department of International Development, UK Medical Research Council, and Wellcome Trust. Thematic analysis of the data demonstrates their funding schemes promote health systems research with (up to) five key features that advance health equity: being conducted with worst‐off populations, focusing on research topics that advance equitable health systems, having LMIC ownership of the research agenda, strengthening LMIC research capacity, and having an impact on health disparities. The different types of incentives that encouraged proposed projects to have these features are identified and classified by their strength (strong, moderate, weak). It is suggested that research funders ought to create and maintain funding schemes with strong incentives for the features identified above in order to more effectively help reduce global health disparities.     

The UK’s 100,000 Genomes Project: manifesting policymakers’ expectations

The UK’s 100,000 Genomes Project has the aim of sequencing 100,000 genomes from UK National Health Service (NHS) patients while concomitantly transforming clinical care such that whole genome sequencing becomes routine clinical practice in the UK. Policymakers claim that the project will revolutionize NHS care. We wished to explore the 100,000 Genomes Project, and in particular, the extent to which policymaker claims have helped or hindered the work of those associated with Genomics England – the company established by the Department of Health to deliver the project. We interviewed 20 individuals linked to, or working for Genomics England. Interviewees had double-edged views about the context within which they were working. On the one hand, policymakers’ expectations attached to the venture were considered vacuous “genohype”; on the other hand, they were considered the impetus needed for those trying to advance genomic research into clinical practice. Findings should be considered for future genomes projects.     

Evaluation of existing sustainable infrastructure rating systems for their application in developing countries

Several sustainable building rating systems were created worldwide during the last decades due to economic growth and the significance of environmental impact associated with the building industry. Similar infrastructure rating tools have started to be developed and implemented, being highly necessary to promote its development. Even though the existing sustainable infrastructure rating systems are focused on advanced economies, growing environmental concerns are increasing the need for new systems in the Developing World. This research analyses some of the mainstream infrastructure rating frameworks such as Envision (USA), Civil Engineering Environmental Quality (CEEQUAL) assessment (UK) and Infrastructure Sustainability (IS) Rating Tool (Australia) from the perspective of the Triple Bottom Line (economy, environment and society), in order to determine the effectiveness of their application in the context of the least developed countries. The analysis revealed that the three tools are biased towards the environmental dimension and are mainly oriented to developed countries. Consequently, the foundations on which these systems are based need to be further developed and enhanced to be of real relevance in poorer nations by balancing the weight of sustainable pillars, incorporating effective management guidelines and development goals set by United Nations declarations, and considering impacts beyond the single project framework.