Search

Background: Academic clinical trials play a fundamental role in the development of new treatments, the repurposing of existing treatments and in addressing areas of unmet clinical need. With cancer treatments increasingly targeted at molecular subtypes, and with priority placed on developing new treatments for rare tumour types, the need for international trial participation to access sufficient patient numbers for successful trial conduct is growing. However, lack of harmonisation of international legal, ethical and financial systems can make this challenging and the cost and effort of conducting trials internationally can be considered prohibitive, particularly where the sample size is comparatively small.Methods: The Institute of Cancer Research - Clinical Trials and Statistics Unit (ICR-CTSU) is a UK-based academic clinical trials unit that specialises in the design, conduct and analysis of clinical trials of cancer treatments with an expanding portfolio of trials in molecular subtypes of breast and urological cancers and in other rare cancer types. Implementing appropriate mechanisms to enable international participation has therefore been imperative. In this article, we explain how we have approached the challenges involved and describe examples of successful international trial conduct, achieved through robust collaborations with academic and industry partners.Conclusion: Conducting academic trials internationally is challenging but can and should be achieved through appropriate governance mechanisms and strong collaborations. [ABSTRACT FROM AUTHOR]

Background: Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers.Methods: We performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.Results: The following barriers to randomised clinical trials were identified: inadequate knowledge of clinical research and trial methodology; lack of funding; excessive monitoring; restrictive privacy law and lack of transparency; complex regulatory requirements; and inadequate infrastructures. There is a need for more pragmatic randomised clinical trials conducted with low risks of systematic and random errors, and multinational cooperation is essential.Conclusions: The present paper presents major barriers to randomised clinical trials. It also underlines the value of using a pan-European-distributed infrastructure to help investigators overcome barriers for multi-country trials in any disease area. [ABSTRACT FROM AUTHOR]

Background: Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013.Methods: The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis.Results: The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p < 0.001) while phase 3 trials were much more prevalent in all nine representative countries than in the USA. A larger number of "child" age group trials was performed in Poland (OR 1.852, p < 0.001), Israel (OR 1.546, p = 0.005), and South Africa (OR 1.963, p < 0.001) than in the USA. Multivariate analysis showed that health care expenditure per capita, Economic Freedom Index, Human Capital Index, and Intellectual Property Rights Index could explain the variance of regional distribution of clinical trials by 63.6%.Conclusions: The globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints. [ABSTRACT FROM AUTHOR]

Background: The costs of medical research are a concern. Clinical Trials Units (CTUs) need to better understand variations in the costs of their activities.Methods: Representatives of ten CTUs and two grant-awarding bodies pooled their experiences in discussions over 1.5 years. Five of the CTUs provided estimates of, and written justification for, costs associated with CTU activities required to implement an identical protocol. The protocol described a 5.5-year, nonpharmacological randomized controlled trial (RCT) conducted at 20 centres. Direct and indirect costs, the number of full time equivalents (FTEs) and the FTEs attracting overheads were compared and qualitative methods (unstructured interviews and thematic analysis) were used to interpret the results. Four members of the group (funding-body representatives or award panel members) reviewed the justification statements for transparency and information content. Separately, 163 activities common to trials were assigned to roles used by nine CTUs; the consistency of role delineation was assessed by Cohen's κ.Results: Median full economic cost of CTU activities was £769,637 (range: £661,112 to £1,383,323). Indirect costs varied considerably, accounting for between 15% and 59% (median 35%) of the full economic cost of the grant. Excluding one CTU, which used external statisticians, the total number of FTEs ranged from 2.0 to 3.0; total FTEs attracting overheads ranged from 0.3 to 2.0. Variation in directly incurred staff costs depended on whether CTUs: supported particular roles from core funding rather than grants; opted not to cost certain activities into the grant; assigned clerical or data management tasks to research or administrative staff; employed extensive on-site monitoring strategies (also the main source of variation in non-staff costs). Funders preferred written justifications of costs that described both FTEs and indicative tasks for funded roles, with itemised non-staff costs. Consistency in role delineation was fair (κ = 0.21-0.40) for statisticians/data managers and poor for other roles (κ < 0.20).Conclusions: Some variation in costs is due to factors outside the control of CTUs such as access to core funding and levels of indirect costs levied by host institutions. Research is needed on strategies to control costs appropriately, especially the implementation of risk-based monitoring strategies. [ABSTRACT FROM AUTHOR]

Background: Global healthcare innovation networks nowadays have expanded beyond developed countries with many developing countries joining the force and becoming important players. China, in particular, has seen a significant increase in the number of innovative firms and research organizations stepping up to the global network in recent years. Nevertheless, the intense Research and Development input has not brought about the expectable output. While China is ascending at a great speed to a leading position worldwide in terms of Research and Development investment, scientific publications and patents, the innovation capabilities in the pharmaceutical sector remain weak.Discussion: This study discusses the challenges and opportunities for pharmaceutical innovation in China. One hand, academic, industrial, institutional and financial constraints were found to be the major and inevitable barriers hindering the development of drug innovation. On the other hand, unique advantages had been observed which included growing pharmaceutical market, Research and Development funding, distinctive source, and international cooperation. The most important thing for China's pharmaceutical sector to leap forward is to break though innovation barriers and integrate own advantages into global value-chain of healthcare product development. [ABSTRACT FROM AUTHOR]

An essential, but often overlooked part of health promotion and development support to achieve self-sufficiency in developing countries is the concomitant need to build and strengthen research capacity. This is even more challenging and critical in the area of sexual and reproductive health because of diverse interplay of socio cultural, religious, economic factors in relation to reproductive health. This paper presents the case study of HRP's efforts to build research capacity in Latin America by studying and analyzing the 5-year history of institutional development support to an institution in Paraguay. In reviewing the efforts, we identify the strengths in the approaches used by HRP, the challenges and outcomes of the process and we present recommendations for future efforts to strengthen research capacity to improve sexual and reproductive health. The authors call for greater support from and collaborative efforts of developmental partners and governments to strengthen research capacity in low and middle-income countries to improve sexual and reproductive health. [ABSTRACT FROM AUTHOR]

Background: Government- and charity-funded medical research and private sector research and development (R&D) are widely held to be complements. The only attempts to measure this complementarity so far have used data from the United States of America and are inevitably increasingly out of date. This study estimates the magnitude of the effect of government and charity biomedical and health research expenditure in the United Kingdom (UK), separately and in total, on subsequent private pharmaceutical sector R&D expenditure in the UK.Methods: The results for this study are obtained by fitting an econometric vector error correction model (VECM) to time series for biomedical and health R&D expenditure in the UK for ten disease areas (including 'other') for the government, charity and private sectors. The VECM model describes the relationship between public (i.e. government and charities combined) sector expenditure, private sector expenditure and global pharmaceutical sales as a combination of a long-term equilibrium and short-term movements.Results: There is a statistically significant complementary relationship between public biomedical and health research expenditure and private pharmaceutical R&D expenditure. A 1% increase in public sector expenditure is associated in the best-fit model with a 0.81% increase in private sector expenditure. Sensitivity analysis produces a similar and statistically significant result with a slightly smaller positive elasticity of 0.68. Overall, every additional £1 of public research expenditure is associated with an additional £0.83-£1.07 of private sector R&D spend in the UK; 44% of that additional private sector expenditure occurs within 1 year, with the remainder accumulating over decades. This spillover effect implies a real annual rate of return (in terms of economic impact) to public biomedical and health research in the UK of 15-18%. When combined with previous estimates of the health gain that results from public medical research in cancer and cardiovascular disease, the total rate of return would be around 24-28%.Conclusion: Overall, this suggests that government and charity funded research in the UK crowds in additional private sector R&D in the UK. The implied historical returns from UK government and charity funded investment in medical research in the UK compare favourably with the rates of return achieved on investments in the rest of the UK economy and are greatly in excess of the 3.5% real annual rate of return required by the UK government to public investments generally. [ABSTRACT FROM AUTHOR]

Background Strengthening health research capacity in low- and middle-income countries remains a major policy goal. The Health Research Capacity Strengthening (HRCS) Global Learning (HGL) program of work documented experiences of HRCS across sub-Saharan Africa. Methods We reviewed findings from HGL case studies and reflective papers regarding the dynamics of HRCS. Analysis was structured with respect to common challenges in such work, identified through a multi-dimensional scaling analysis of responses from 37 participants at the concluding symposium of the program of work. Results Symposium participants identified 10 distinct clusters of challenges: engaging researchers, policymakers, and donors; securing trust and cooperation; finding common interest; securing long-term funding; establishing sustainable models of capacity strengthening; ensuring Southern ownership; accommodating local health system priorities and constraints; addressing disincentives for academic engagement; establishing and retaining research teams; and sustaining mentorship and institutional support. Analysis links these challenges to three key and potentially competing drivers of the political economy of health research: an enduring model of independent researchers and research leaders, the globalization of knowledge and the linked mobility of (elite) individuals, and institutionalization of research within universities and research centres and, increasingly, national research and development agendas. Conclusions We identify tensions between efforts to embrace the global 'Community of Science' and the promotion and protection of national and institutional agendas in an unequal global health research environment. A nuanced understanding of the dynamics and implications of the uneven global health research landscape is required, along with a willingness to explore pragmatic models that seek to balance these competing drivers. [ABSTRACT FROM AUTHOR]

Introduction: An impactful clinical trial will have real-life benefits for patients and society beyond the academic environment. This study analyses case studies of cancer trials to understand how impact is evidenced for cancer trials and how impact evaluation can be more routinely adopted and improved.Methods: The United Kingdom (UK) Government allocates research funding to higher-education institutions based on an assessment of the institutions' previous research efforts, in an exercise known as the Research Excellence Framework (REF). In addition to each institution's journal publications and research environment, for the first time in 2014, allocation of funding was also dependent on an evaluation of the wider, societal impact of research conducted. In the REF2014, impact assessment was performed by evaluation of impact case studies. In this study, case studies (n = 6637) submitted by institutions for the REF2014 were accessed and those focussing on cancer trials were identified. Manual content analysis was then used to assess the characteristics of the cancer trials discussed in the case studies, the impact described and the methods used by institutions to demonstrate impact.Results: Forty-six case studies describing 106 individual cancer trials were identified. The majority were phase III randomised controlled trials and those recruiting patients with breast cancer. A list of indicators of cancer trial impact was generated using the previous literature and developed inductively using these case studies. The most common impact from a cancer trial identified in the case studies was on policy, in particular citation of trial findings in clinical guidelines. Impact on health outcomes and the economy were less frequent and health outcomes were often predicted rather than evidenced. There were few descriptions identified of trialists making efforts to maximise trial impact.Discussion: Cancer trial impact narratives for the next REF assessment exercise in 2021 can be improved by evidencing actual rather than predicted Impact, with a clearer identification of the beneficiaries of cancer trials and the processes through which trial results are used. Clarification of the individuals responsible for performing impact evaluations of cancer trials and the provision of resources to do so needs to be addressed if impact evaluation is to be sustainable. [ABSTRACT FROM AUTHOR]