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Value of information (VOI) analyses can help policy makers make informed decisions about whether to conduct and how to design future studies. Historically a computationally expensive method to compute the expected value of sample information (EVSI) restricted the use of VOI to simple decision models and study designs. Recently, 4 EVSI approximation methods have made such analyses more feasible and accessible. Members of the Collaborative Network for Value of Information (ConVOI) compared the inputs, the analyst's expertise and skills, and the software required for the 4 recently developed EVSI approximation methods. Our report provides practical guidance and recommendations to help inform the choice between the 4 efficient EVSI estimation methods. More specifically, this report provides: (1) a step-by-step guide to the methods' use, (2) the expertise and skills required to implement the methods, and (3) method recommendations based on the features of decision-analytic problems. [ABSTRACT FROM AUTHOR]

This commentary makes the case for increased investment in the development of improved contraceptive and multipurpose prevention technologies (MPTs) that better meet the needs and preferences of users, increase the methods' acceptability and use, and ultimately decrease unintended pregnancy. Methods that are inexpensive, user-controlled, and shelf-stable could help address challenges posed by weak supply chains and healthcare systems. New MPTs that protect against pregnancy and sexually transmitted infections (STIs), including HIV, could simultaneously address multiple sexual and reproductive health needs. Although promising scientific leads exist, the high costs and risks associated with contraceptive development has contributed to underinvestment. The public sector, philanthropies, and the pharmaceutical industry have decreased or eliminated investments in contraceptive research and development (R&D) in recent decades. Greater financial and policy support are required for the eventual introduction of new and improved contraceptives and MPTs. [ABSTRACT FROM AUTHOR]

Objective: The expected value of sample information (EVSI) quantifies the economic benefit of reducing uncertainty in a health economic model by collecting additional information. This has the potential to improve the allocation of research budgets. Despite this, practical EVSI evaluations are limited partly due to the computational cost of estimating this value using the gold-standard nested simulation methods. Recently, however, Heath et al. developed an estimation procedure that reduces the number of simulations required for this gold-standard calculation. Up to this point, this new method has been presented in purely technical terms.Study Design: This study presents the practical application of this new method to aid its implementation. We use a worked example to illustrate the key steps of the EVSI estimation procedure before discussing its optimal implementation using a practical health economic model.Methods: The worked example is based on a three-parameter linear health economic model. The more realistic model evaluates the cost-effectiveness of a new chemotherapy treatment, which aims to reduce the number of side effects experienced by patients. We use a Markov model structure to evaluate the health economic profile of experiencing side effects.Results: This EVSI estimation method offers accurate estimation within a feasible computation time, seconds compared to days, even for more complex model structures. The EVSI estimation is more accurate if a greater number of nested samples are used, even for a fixed computational cost.Conclusions: This new method reduces the computational cost of estimating the EVSI by nested simulation. [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]

The different countries that death and dying researchers reside within often shape not only research agendas but also research methodologies. The United Kingdom and the United States are two examples of countries that share a common language and intellectual history but their discourses on death have been very different. These differences are partly explained through cultural practices, and also government funding of research, definitions of death and end-of-life planning education. In this article, we argue that early death scholarship in the United States impacted death research and outcomes in both the US and the UK, but that recent scholarship in both countries has caused the two countries to diverge in two major areas: (1) the methodological approaches to death studies and (2) the educational training of medical and hospice personnel in direct contact with the dying. We argue that in order for death studies to fully benefit from trans-Atlantic dialogue on death, both countries need to move towards a more integrated trans-disciplinary model. [ABSTRACT FROM PUBLISHER]

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 Industry funders can simply provide money or collaborate in trial design, analysis or reporting of clinical trials. Our aim was to assess the impact of industry collaboration on trial methodology and results of randomised controlled trials (RCT). Methods We searched PubMed for oncology RCTs published May 2013 to December 2015 in peer-reviewed journals with impact factor > 5 requiring reporting of funder role. Two authors extracted methodologic (primary end-point; blinding of the patient, clinician and outcomes assessor; and analysis) and outcome data. We used descriptive statistics and two-sided Fisher exact tests to compare characteristics of trials with collaboration, with industry funding only, and without industry funding. Results We included 224 trials. Compared to those without industry funding, trials with collaboration used more placebo control (RR 3·59, 95% CI [1·88–6·83], p < 0001), intention-to-treat analysis (RR 1·32, 95% CI [1·04–1·67], p = 02), and blinding of patients (RR 3·05, 95% CI [1·71–5·44], p < 0001), clinicians (RR 3·36, 95% CI [1·83–6·16], p≤·001) and outcomes assessors (RR 3·03, 95% CI [1·57–5·83], p = 0002). They did not differ in use of overall survival as a primary end-point (RR 1·27 95% CI [0·72–2·24]) and were similarly likely to report positive results (RR 1·11 95% CI [0·85–1·46], p = 0.45). Studies with funding only did not differ from those without funding. Conclusions Oncology RCTs with industry collaboration were more likely to use some high-quality methods than those without industry funding, with similar rates of positive results. Our findings suggest that collaboration is not associated with trial outcomes and that mandatory disclosure of funder roles may mitigate bias. [ABSTRACT FROM AUTHOR]

Background: The extent to which trial-level factors differentially influence accrual to trials has not been comprehensively studied. Our objective was to evaluate the empirical relationship and predictive properties of putative risk factors for low accrual in the National Cancer Institute's (NCI's) Cooperative Group Program, now the National Clinical Trials Network (NCTN).Methods: Data from 787 phase II/III adult NCTN-sponsored trials launched between 2000 and 2011 were used to develop a logistic regression model to predict low accrual, defined as trials that closed with or were accruing at less than 50% of target; 46 trials opened between 2012 and 2013 were used for prospective validation. Candidate predictors were identified from a literature review and expert interviews; final predictors were selected using stepwise regression. Model performance was evaluated by calibration and discrimination via the area under the curve (AUC). All statistical tests were two-sided.Results: Eighteen percent (n = 145) of NCTN-sponsored trials closed with low accrual or were accruing at less than 50% of target three years or more after initiation. A multivariable model of twelve trial-level risk factors had good calibration and discrimination for predicting trials with low accrual (AUC in trials launched 2000-2011 = 0.739, 95% confidence interval [CI] = 0.696 to 0.783]; 2012-2013: AUC = 0.732, 95% CI = 0.547 to 0.917). Results were robust to different definitions of low accrual and predictor selection strategies.Conclusions: We identified multiple characteristics of NCTN-sponsored trials associated with low accrual, several of which have not been previously empirically described, and developed a prediction model that can provide a useful estimate of accrual risk based on these factors. Future work should assess the role of such prediction tools in trial design and prioritization decisions. [ABSTRACT FROM AUTHOR]

Background: America's racial and ethnic composition is changing so rapidly that minority groups are expected to constitute almost half of the U.S. population by 2060. Special efforts are needed to effectively recruit and retain members of racial and ethnic minority groups in health-related research studies, but the information available on time and costs associated with their recruitment is limited. Objectives: The aim of this study was to describe and compare the time and monetary costs associated with recruiting and interviewing a diverse sample of older adults living in south Florida. Methods: Men and women aged 60 years and older from four ethnic groups-African American, Afro-Caribbean, Hispanic American, and European American-were recruited to participate in a longitudinal study of healthy aging. Costs for study activities (including recruitment, scheduling sessions, interviewing, file scoring, log updating, blood specimen analysis and storage, data analysis, and monetary compensation to participants) were determined after 100 weeks of data collection. Results: Altogether, 483 participants completed the study in the first 100 weeks. The total cost for each participant ranged from $265 to $576. Each successful enrollment required an average of 1.83 hours for recruitment and scheduling of the interviews. The time to interview African American and Afro-Caribbeans was greater than the time needed to interview Hispanic American and European American participants. Discussion: To develop more accurate budgets for recruitment of minority individuals into research studies and to use the limited resources in an effective way, careful planning and ongoing monitoring of costs are essential. [ABSTRACT FROM AUTHOR]

Comparative effectiveness research (CER) has the potential to slow health care spending growth by focusing resources on health interventions that provide the most value. In this article, we discuss issues surrounding CER and its implementation and apply these methods to a salient clinical example: treatment of prostate cancer. Physicians have several options for treating patients recently diagnosed with localized disease, including removal of the prostate (radical prostatectomy), treatment with radioactive seeds (brachytherapy), radiation therapy (IMRT), or--if none of these are pursued--active surveillance. Using a commercial health insurance claims database and after adjustment for comorbid conditions, we estimate that the additional cost of treatment with radical prostatectomy is $7,300, while other alternatives are more expensive--$19,000 for brachytherapy and $46,900 for IMRT. However a review of the clinical literature uncovers no evidence that justifies the use of these more expensive approaches. These results imply that if patient management strategies were shifted to those supported by CER-based criteria, an estimated $1.7 to $3.0 billion (2009 present value) could be saved each year. [ABSTRACT FROM AUTHOR]

The genetics community is increasingly concerned that patents might lead to restricted access to research and health care. We explore various measures that are designed to render patented genetic inventions accessible to further use in research, and to diagnosis and/or treatment. They include the often-recited research or experimental-use exemption, conventional one-to-one licensing and compulsory licensing, as well as patent pools and clearing-house mechanisms. The last two alternatives deserve special attention in the area of human genetics. [ABSTRACT FROM AUTHOR]

While debate continues as to whether genetic sequences, which many argue represent natural phenomena rather than inventions, should be subject to standard patent protections, issuance of patents that claim DNA sequences remains common practice. In an attempt to insulate researchers from patent claims that could hinder scientific progress, many countries have provided general exemptions for scientific research. However, there is no international consensus about the extent of required protections, and even existing exemptions vary widely in clarity and are limited in practical application. We believe that gene patents raise several unique issues that are inadequately handled by the current research exemptions. [ABSTRACT FROM AUTHOR]

Background: Previously published research by the authors found that returns on research and development (R&D) for drugs introduced into the US market in the 1970s and 1980s were highly skewed and that the top decile of new drugs accounted for close to half the overall market value. In the 1990s, however, the R&D environment for new medicines underwent a number of changes including the following: the rapid growth of managed-care organisations; indications that R&D costs were rising at a rate faster than that of overall inflation; new market strategies of major firms aimed at simultaneous launches across world markets; and the increased attention focused on the pharmaceutical industry in the political arena.Objective: The aim of this study was to examine the worldwide returns on R&D for drugs introduced into the US market in the first half of the 1990s, given that there have been significant changes to the R&D environment for new medicines over the past decade or so.Results: Analysis of new drugs entering the market from 1990 to 1994 resulted in findings similar to those of the earlier research - pharmaceutical R&D is characterised by a highly skewed distribution of returns and a mean industry internal rate of return modestly in excess of the cost of capital.Conclusions: Although the distribution of returns on R&D for new drugs continues to be highly skewed, the analysis reveals that a number of dynamic forces are currently at work in the industry. In particular, R&D costs as well as new drug introductions, sales and contribution margins increased significantly compared with their 1980s values. [ABSTRACT FROM AUTHOR]

We describe past NIH funding for tobacco/nicotine-related research, using data from the CRISP computerized database of NIH grants awarded in 1975, 1980, 1985, 1990, and 1995 (last year available). Two independent raters identified extramural grants whose investigators listed a nicotine/tobacco-related keyword as a primary descriptor for 1975, 1980, 1985, 1990, and 1995. From 1975 to 1985 extramural funding for nicotine/tobacco research (corrected for inflation) increased almost fourfold. From 1985 to 1995, funding increased minimally (< 20%). In 1995, NIH expended $92.1 million on research whose primary interest was nicotine or tobacco. This represented 1.1% of the overall NIH extramural budget. Over time, when contract funding increased, investigator-initiated R01 funding decreased. Nicotine/tobacco research was spread across 18 institutes. Although tobacco use accounts for 20% of all US mortality, historically only 1% of the NIH's budget has focused on nicotine or tobacco. Among nicotine/tobacco grants funded, investigator-initiated research appears to have been limited due to large contracts for clinical trials. Nicotine/tobacco research has no home institute. Funding for nicotine/tobacco research needs to be increased and better coordinated. [ABSTRACT FROM AUTHOR]

Background: Recently, patients who received induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma were found to have survival advantages compared with those receiving concurrent chemoradiotherapy alone in two large randomized trials. Based on these two trials, we present a cost-effectiveness analysis to compare gemcitabine and cisplatin (GP) versus cisplatin, fluorouracil, and docetaxel (TPF) for induction chemotherapy to treat locoregionally advanced nasopharyngeal carcinoma.Methods: We constructed a Markov model to compare the cost and effectiveness of GP versus TPF. Clinical data including the frequency of adverse events, recurrence and death obtained from two randomized phase III trials were used to calculate transition probabilities and costs. Health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollars per quality-adjusted life-year (QALY), were calculated, and incremental cost-effectiveness ratios less than $27,534.25/QALY (3 × the per capita GDP of China, 2018) were considered cost-effective. One-way sensitivity and probabilistic sensitivity analyses explored the robustness of the model.Results: Our base case model found that the total cost was $53,082.68 in the GP group and $45,482.66 in the TPF group. The QALYs were 6.82 and 4.11, respectively. The incremental cost-effectiveness ratio favoured the GP regimen, at an incremental cost of $2,804.44 per QALY. The probabilistic sensitivity analysis found that treatment with the GP regimen was cost-effective 100% of the time at a willingness-to-pay threshold of $27,534.25‬/QALY.Conclusion: In this model, GP was estimated to be cost-effective compared with cisplatin, fluorouracil, and docetaxel for patients with locoregionally advanced nasopharyngeal carcinoma from the payer's perspectives in the China. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between scientometrics and the production of intellectual research. The author comments on the impact of economic and political conditions on research methodology and assessment. The influence of these factors on academic corruption, scholarly publishing, and research output is also explored.

The author discusses the fair participant selection in a certain clinical trial. She notes that the patients who will participate must remain in close proximity to the site for the entire duration of the study. The author emphasizes that groups should not be excluded from the opportunity to participate without a good scientific reason or particular susceptibility to risk, otherwise the trial would indeed be unfair and unethical.

Background: The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices. Objectives: To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice. Methods: From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes. Results: In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice. Conclusions: OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects. [ABSTRACT FROM AUTHOR]