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1.
Katy Benjamin Margaret K. Vernon Donald L. Patrick Eleanor Perfetto Sandra Nestler-Parr Laurie Burke 《Value in health》2017,20(7):838-855
Background
Rare diseases (RDs) affect a small number of people within a population. About 5000 to 8000 distinct RDs have been identified, with an estimated 6% to 8% of people worldwide suffering from an RD. Approximately 75% of RDs affect children. Frequently, these conditions are heterogeneous; many are progressive. Regulatory incentives have increased orphan drug designations and approvals.Objective
To develop emerging good practices for RD outcomes research addressing the challenges inherent in identifying, selecting, developing, adapting, and implementing patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments for use in RD clinical trials.Good Practices for Outcomes Research
This report outlines the challenges and potential solutions in determining clinical outcomes for RD trials. It follows the US Food and Drug Administration Roadmap to Patient-Focused Outcome Measurement in Clinical Trials. The Roadmap consists of three columns: 1) Understanding the Disease or Condition, 2) Conceptualizing Treatment Benefit, and 3) Selecting/Developing the Outcome Measure. Challenges in column 1 include factors such as incomplete natural history data and heterogeneity of disease presentation and patient experience. Solutions include using several information sources, for example, clinical experts and patient advocacy groups, to construct the condition’s natural history and understand treatment patterns. Challenges in column 2 include understanding and measuring treatment benefit from the patient’s perspective, especially given challenges in defining the context of use such as variations in age or disease severity/progression. Solutions include focusing on common symptoms across patient subgroups, identifying short-term outcomes, and using multiple types of COA instruments to measure the same constructs. Challenges in column 3 center around the small patient population and heterogeneity of the condition or study sample. Few disease-specific instruments for RDs exist. Strategies include adapting existing instruments developed for a similar condition or that contain symptoms of importance to the RD patient population, or using a generic instrument validated for the context of use.Conclusions
This report provides state-of-the-art solutions to patient-reported outcome (PRO) and observer-reported outcome (ObsRO) assessments challenges in clinical trials of patients with RDs. These recommended solutions are both pragmatic and creative and posed with clear recognition of the global regulatory context used in RD clinical development programs. 相似文献2.
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Objectives
To evaluate the national regulatory, health technology assessment (HTA), and reimbursement pathways for public health care in Australia, Canada, England, and Scotland, to compare initial Canadian national HTA recommendations with the initial decisions of the other HTA agencies, and to identify factors for differing national HTA recommendations between the four HTA agencies.Methods
Information from the public domain was used to develop a regulatory process map for each jurisdiction and to compare the HTA agencies’ reimbursement recommendations. Medicines that were reviewed by all four agencies and received a negative recommendation from only one agency were selected as case studies.Results
All four countries have a national HTA agency. Their reimbursement recommendations are guided by both clinical efficacy and cost-effectiveness, and the necessity for patient input. Their activities, however, vary because of different mandates and their unique political, social, and population needs. All have an implicit or explicit quality-adjusted life-year threshold. The seven divergent case studies demonstrate examples in which new medicine-indication pairs have been rejected because of uncertainties surrounding a range of factors including cost-effectiveness, comparator choice, clinical benefit, safety, trial design, and submission timing.Conclusions
The four HTA agencies selected for inclusion in this study share common factors, including a focus on clinical efficacy and cost-effectiveness in their decision-making processes. The differences in recommendations could be considered to be due to an individual agency’s approach to risk perception, and the comparator choice used in clinical and cost-effectiveness studies. 相似文献5.
Background
It has been suggested that differences in health technology assessment (HTA) processes among countries, particularly within Europe, have led to inequity in patient access to new medicines.Objectives
To provide an up-to-date snapshot analysis of the present status of HTA and reimbursement systems in select European countries, and to investigate the implications of these processes, especially with regard to delays in market and patient access.Methods
HTA and reimbursement processes were assessed through a review of published and gray literature, and through a series of interviews with HTA experts. To quantify the impact of differences among countries, we conducted case studies of 12 products introduced since 2009, including 10 cancer drugs.Results
In addition to the differences in HTA and reimbursement processes among countries, the influence of particular sources of information differs among HTA bodies. The variation in the time from the authorization by the European Medicines Agency to the publication of HTA decisions was considerable, both within and among countries, with a general lack of transparency as to why some assessments take longer than others. In most countries, market access for oncology products can occur outside the HTA process, with sales often preceding HTA decisions.Conclusions
It is challenging even for those with considerable personal experience in European HTA processes to establish what is really happening in market access for new drugs. We recommend that efforts should be directed toward improving transparency in HTA, which should, in turn, lead to more effective processes. 相似文献6.
Marc L. Berger Harold Sox Richard J. Willke Diana L. Brixner Hans‐Georg Eichler Wim Goettsch David Madigan Amr Makady Sebastian Schneeweiss Rosanna Tarricone Shirley V. Wang John Watkins C. Daniel Mullins 《Value in health》2017,20(8):1003-1008
Purpose
Real‐world evidence (RWE) includes data from retrospective or prospective observational studies and observational registries and provides insights beyond those addressed by randomized controlled trials. RWE studies aim to improve health care decision making.Methods
The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) created a task force to make recommendations regarding good procedural practices that would enhance decision makers’ confidence in evidence derived from RWD studies. Peer review by ISPOR/ISPE members and task force participants provided a consensus‐building iterative process for the topics and framing of recommendations.Results
The ISPOR/ISPE Task Force recommendations cover seven topics such as study registration, replicability, and stakeholder involvement in RWE studies. These recommendations, in concert with earlier recommendations about study methodology, provide a trustworthy foundation for the expanded use of RWE in health care decision making.Conclusion
The focus of these recommendations is good procedural practices for studies that test a specific hypothesis in a specific population. We recognize that some of the recommendations in this report may not be widely adopted without appropriate incentives from decision makers, journal editors, and other key stakeholders. 相似文献7.
Amr Makady Renske ten Ham Anthonius de Boer Hans Hillege Olaf Klungel Wim Goettsch 《Value in health》2017,20(4):520-532
Background
Randomized controlled trials provide robust data on the efficacy of interventions rather than on effectiveness. Health technology assessment (HTA) agencies worldwide are thus exploring whether real-world data (RWD) may provide alternative sources of data on effectiveness of interventions. Presently, an overview of HTA agencies’ policies for RWD use in relative effectiveness assessments (REA) is lacking.Objectives
To review policies of six European HTA agencies on RWD use in REA of drugs. A literature review and stakeholder interviews were conducted to collect information on RWD policies for six agencies: the Dental and Pharmaceutical Benefits Agency (Sweden), the National Institute for Health and Care Excellence (United Kingdom), the Institute for Quality and Efficiency in Healthcare (Germany), the High Authority for Health (France), the Italian Medicines Agency (Italy), and the National Healthcare Institute (The Netherlands). The following contexts for RWD use in REA of drugs were reviewed: initial reimbursement discussions, pharmacoeconomic analyses, and conditional reimbursement schemes. We identified 13 policy documents and 9 academic publications, and conducted 6 interviews.Results
Policies for RWD use in REA of drugs notably differed across contexts. Moreover, policies differed between HTA agencies. Such variations might discourage the use of RWD for HTA.Conclusions
To facilitate the use of RWD for HTA across Europe, more alignment of policies seems necessary. Recent articles and project proposals of the European network of HTA may provide a starting point to achieve this. 相似文献8.
Chidubem B. Ogwulu Louise J. Jackson Philip Kinghorn Tracy E. Roberts 《Value in health》2017,20(8):1180-1197
Background
A broad literature on health state utility values exists, but compared with chronic health states (HSs), issues surrounding the valuation of temporary health states (THSs) have been poorly explored.Objectives
To assess the methods used by previous studies to value HSs that are considered temporary so as to determine the strengths and limitations associated with various approaches and to inform future study designs.Methods
A systematic review was undertaken to explore the methods used, assess how the valuation was conducted for diseases that might lead to HSs deemed as temporary, and identify the challenges encountered in the valuation of THSs.Results
Of the 36 relevant studies, 22 were explicit that the HS being valued was temporary. Most of the studies used more than one technique (often incorporating both conventional and adapted approaches). In using adapted techniques, the primary challenge was identifying an appropriate intermediate “anchor” HS and the possibility of negative utilities.Conclusions
There is no agreement on the most methodologically robust approach to THS valuation. Valuation is complex and important issues relating to the validity, practicality, and reliability of the techniques used were not adequately covered by most of the studies identified. 相似文献9.
Britta Olberg Sabine Fuchs Dimitra Panteli Matthias Perleth Reinhard Busse 《Value in health》2017,20(10):1420-1426
Background
The aim of this study was to examine the scientific evidence on clinical effectiveness and safety used in health technology assessments (HTAs) of high-risk medical devices (MDs) in Europe.Methods
We applied a systematic approach to identify European institutions involved in HTA and to select reports assessing MDs considered high-risk according to the definition in the new German health care regulation 4137h. Reports published between 2010 and 2015 were considered in our subsequent analysis. We used a structured tool based on widely accepted methodologic principles from Drummond’s framework to extract key information on the clinical evidence considered in the reports.Results
Out of 1376 identified reports, 93 were eligible for analysis. All reports based their assessment primarily on direct evidence, in most cases (68%) identified through an independent systematic literature search. In more than half the identified studies considered in the reports, clinical evidence for demonstration of effectiveness and safety was of moderate or low quality. Even when systematic reviews and randomized controlled trials were available for assessment, most studies showed an unclear or high risk of bias.Conclusions
This study confirms that the quality of scientific evidence used in HTA of high-risk MDs is low and therefore the use of evidence needs improvement. The European Commission recently updated the regulation on MDs but mainly focused on the safety of materials and the CE (Conformité Européene [European Conformity]) mark. Our results show that additional changes are necessary, specifically with regard to the marketing authorization process of MDs, with stricter quality requirements based on methodologically robust trials, possibly in combination with other evidence sources. 相似文献10.
Wija Oortwijn Domino Determann Krijn Schiffers Siok Swan Tan Jeroen van der Tuin 《Value in health》2017,20(8):1121-1130
Objectives
To assess the level of comprehensiveness of health technology assessment (HTA) practices around the globe and to formulate recommendations for enhancing legitimacy and fairness of related decision-making processes.Methods
To identify best practices, we developed an evaluation framework consisting of 13 criteria on the basis of the INTEGRATE-HTA model (integrative perspective on assessing health technologies) and the Accountability for Reasonableness framework (deliberative appraisal process). We examined different HTA systems in middle-income countries (Argentina, Brazil, and Thailand) and high-income countries (Australia, Canada, England, France, Germany, Scotland, and South Korea). For this purpose, desk research and structured interviews with relevant key stakeholders (N = 32) in the selected countries were conducted.Results
HTA systems in Canada, England, and Scotland appear relatively well aligned with our framework, followed by Australia, Germany, and France. Argentina and South Korea are at an early stage, whereas Brazil and Thailand are at an intermediate level. Both desk research and interviews revealed that scoping is often not part of the HTA process. In contrast, providing evidence reports for assessment is well established. Indirect and unintended outcomes are increasingly considered, but there is room for improvement. Monitoring and evaluation of the HTA process is not well established across countries. Finally, adopting transparent and robust processes, including stakeholder consultation, takes time.Conclusions
This study presents a framework for assessing the level of comprehensiveness of the HTA process in a country. On the basis of applying the framework, we formulate recommendations on how the HTA community can move toward a more integrated decision-making process using HTA. 相似文献11.
Finn Børlum Kristensen Kristian Lampe Claudia Wild Marina Cerbo Wim Goettsch Lidia Becla 《Value in health》2017,20(2):244-250
Background and Objectives
The HTA Core Model® as a science-based framework for assessing dimensions of value was developed as a part of the European network for Health Technology Assessment project in the period 2006 to 2008 to facilitate production and sharing of health technology assessment (HTA) information, such as evidence on efficacy and effectiveness and patient aspects, to inform decisions.Methods
It covers clinical value as well as organizational, economic, and patient aspects of technologies and has been field-tested in two consecutive joint actions in the period 2010 to 2016. A large number of HTA institutions were involved in the work.Results
The model has undergone revisions and improvement after iterations of piloting and can be used in a local, national, or international context to produce structured HTA information that can be taken forward by users into their own frameworks to fit their specific needs when informing decisions on technology. The model has a broad scope and offers a common ground to various stakeholders through offering a standard structure and a transparent set of proposed HTA questions. It consists of three main components: 1) the HTA ontology, 2) methodological guidance, and 3) a common reporting structure. It covers domains such as effectiveness, safety, and economics, and also includes domains covering organizational, patient, social, and legal aspects. There is a full model and a focused rapid relative effectiveness assessment model, and a third joint action is to continue till 2020.Conclusion
The HTA Core Model is now available for everyone around the world as a framework for assessing value. 相似文献12.
Eleanor M. Perfetto Jason Harris C. Daniel Mullins Susan dosReis 《Value in health》2018,21(4):386-393
Background
Patient engagement is a transformative strategy for improving value assessment. US value framework developers have increased engagement activities, but more needs to be learned about how to best achieve meaningful patient engagement in value assessment. The objective was to glean good practices in patient engagement emerging from patient community experiences, to be used in value assessment.Methods
The National Health Council Value Workgroup conducted a survey and held a focus group with its member advocacy organizations to gather experiences with value framework developers and views on emerging good practices.Results
Ten of 13 organizations completed the survey; reporting 13 interactions with four framework developers. Most rated experiences as “good” to “very good.” Emerging good practices included (1) engage early; (2) engage a range of patients; (3) leverage patient-provided information, data resources, and outreach mechanisms; (4) be transparent; and (5) appreciate and accommodate resource constraints. Twelve of 13 organizations participated in the focus group, and this produced 30 emerging good practices in four areas: (1) timing; (2) methodology and data; (3) partnering; and (4) characterizing engagement.Discussion
Patient engagement was limited in early development of value frameworks but has increased in the past few years. Patient groups report positive experiences that can serve as emerging good practices. These groups also reported experienced challenges in their interactions and recommended good practices to mitigate those challenges.Conclusions/Recommendations
The growing pool of patient engagement experiences can be translated into good practices to advance a patient-centered, value-driven health care ecosystem. Lessons learned from these early experiences can help establish recommend emerging good practices that can eventually result in best practices and standards in the field. 相似文献13.
Dean A. Regier Deirdre Weymann James Buchanan Deborah A. Marshall Sarah Wordsworth 《Value in health》2018,21(9):1043-1047
Background
Next-generation sequencing (NGS) technologies have seen variable adoption in the clinic. This is partly due to a lack of clinical and economic studies, with the latter increasingly challenged to examine patient preferences for health and nonhealth outcomes (e.g., false-positive rate).Objectives
To conduct a structured review of studies valuing patients’ preference-based utility for NGS outcomes, to highlight identified methodological challenges, and to consider how studies addressed identified challenges.Methods
We searched MEDLINE (PubMed), Embase (Ovid), and Web of Science for published studies examining outcomes from health care decisions informed by NGS. We focused our search on direct elicitations of preference-based utility. We reviewed included studies and qualitatively grouped and summarized stated challenges and solutions by theme.Results
Eleven studies were included. Most of them (n = 6) used discrete choice experiments to value utility. We categorized challenges into four themes: 1) valuing the full range of NGS outcomes, 2) accounting for accuracy and uncertainty surrounding effectiveness, 3) allowing for simultaneous multiple and cascading risks, and 4) incorporating downstream consequences. Studies found strong evidence of utility for NGS information, regardless of health improvement. Investigators addressed challenges by simplifying complex choices, by including health outcomes alongside nonhealth outcomes, and by using multiple elicitation techniques.Conclusions
The breadth and complexity of NGS-derived information makes the technology a unique and challenging application for utility valuation. Failing to account for the utility or disutility of NGS-related nonhealth outcomes may lead to overinvestment or underinvestment in NGS, and so there is a need for research addressing unresolved challenges. 相似文献14.
Kathryn A. Phillips Patricia A. Deverka Deborah A. Marshall Sarah Wordsworth Dean A. Regier Kurt D. Christensen James Buchanan 《Value in health》2018,21(9):1033-1042
Background
Clinical use of next-generation sequencing (NGS) tests has been increasing, but few studies have examined their economic value. Several studies have noted that there are methodological challenges to conducting economic evaluations of NGS tests.Objective
Our objective was to examine key methodological challenges for conducting economic evaluations of NGS tests, prioritize these challenges for future research, and identify how studies have attempted solutions to address these challenges.Methods
We identified challenges for economic evaluations of NGS tests using prior literature and expert judgment of the co-authors. We used a modified Delphi assessment to prioritize challenges, based on importance and probability of resolution. Using a structured literature review and article extraction we then assessed whether published economic evaluations had addressed these challenges.Results
We identified 11 challenges for conducting economic evaluations of NGS tests. The experts identified three challenges as the top priorities for future research: complex model structure, timeframe, and type of analysis and comparators used. Of the 15 published studies included in our literature review, four studies described specific solutions relevant to five of the 11 identified challenges.Conclusions
Major methodological challenges to economic evaluations of NGS tests remain to be addressed. Our results can be used to guide future research and inform decision-makers on how to prioritize research on the economic assessment of NGS tests. 相似文献15.
Marissa Blieden Betts Sandra Milev Meredith Hoog Hyosung Jung Dušan Milenković Yi Qian Ming-Hui Tai Lucie Kutikova Guillermo Villa Christine Edwards 《Value in health》2019,22(2):210-219
Objectives
To identify risk equations for cardiovascular diseases (CVDs) in primary and secondary prevention settings that are used or recommended by health technology assessment (HTA) organizations and in clinical guidelines (CGs).Methods
A targeted literature review was conducted using a two-stage search strategy. First, HTA reviews of manufacturers’ drug submissions, reports from established HTA organizations (Europe, Canada, and Australia), and CGs from countries with and without HTA organizations, including the United States, were identified. Documents published between September 30, 2006 and September 30, 2016, were examined for cardiovascular risk equations, recommendations, and commentaries. Next, publications associated with risk equations and cited by HTA and CG documents were retrieved. This literature was examined to extract commentaries and risk equation study characteristics.Results
The review identified 47 risk equations, 25 in the primary CVD prevention setting (i.e., patients with no CVD history), including 5 for CVD prevention in diabetes and 22 solely in secondary prevention settings; 11 were identified for heart failure, 3 for stroke or transient ischemic attack, 2 for stable angina, and 11 for acute coronary syndrome or related conditions. A small set of primary prevention equations was found to be commonly used by HTAs, whereas secondary prevention equations were less common in HTA documents. CGs provided more risk equations as options than HTA documents.Conclusions
Although there is an abundance of risk equations developed for primary and secondary prevention, there remains a need for additional research to provide sufficient clinical and HTA guidance for risk estimation, particularly in high-risk or secondary prevention settings. 相似文献16.
Objectives
To review recent studies reporting health care expenditures (budgetary impact) for orphan medicinal products (OMPs) in Europe and to contribute to our understanding of the cost drivers of nononcological OMPs by means of an empirical analysis in Germany.Methods
A systematic search for relevant studies on rare diseases was conducted in PubMed and Embase (until December 2016). In addition, annual treatment costs of nononcological OMPs in Germany were analyzed with respect to five explanatory variables: total prevalence of disease, prevalence with added benefit, availability of alternative treatments for the same indication, extent/probability of treatment benefit, and evidence for a treatment effect on mortality.Results
A total of nine studies with specific estimates of the budget impact of OMPs for a total of 11 countries were identified; one study addressed specifically ultrarare diseases. Annual per-capita spending for OMPs ranges from €1.32 in Latvia to €16 in France. Per-patient annual treatment costs vary between €27,811 and €1,647,627 in Germany. On the basis of the German data set, the regression analysis shows that log prevalence has a significant inverse relationship with log annual treatment cost. In this model, doubling the prevalence leads to a 43% decrease in annual treatment cost.Conclusions
Despite per-patient annual treatment costs ranging up to several hundreds of thousands of euros for some OMPs, per-capita spending for OMPs is relatively small. In this study an inverse relationship between prevalence and annual treatment costs was found. 相似文献17.
Background
The number of authorized orphan and non-orphan medicines for rare diseases has increased in Europe. Patient access to these medicines is affected by high costs, weak efficacy/safety evidence, and societal value. European health care systems must determine whether paying for expensive treatments for only a few patients is sustainable.Objectives
This study aimed to evaluate patient access to orphan and non-orphan medicines for rare diseases in 22 European countries during 2005 to 2014.Methods
Medicines for rare diseases from the Orphanet list, authorized during 2005 to 2014, were searched for in the IMS MIDAS Quarterly Sales Data, January 2005 – December 2014 (IQVIA, Danbury, CT). The following three measures were determined for each country: number of available medicines, median time to continuous use, and medicine expenditure. A medicine was considered available if uninterrupted sales within a 1-year period were detected.Results
From 2005 to 2014, 125 medicines were authorized and 112 were found in the search. Of those, between 70 (63%) and 102 (91%) were available in Germany, the United Kingdom, Italy, France, and the Scandinavian countries. These countries were also the fastest to enable continuous use (3–9 mo). Only 27% to 38% of authorized medicines were available in Greece, Ireland, Bulgaria, Romania, and Croatia, which took 1 to 2.6 years to begin continuous use. A country’s expenditure on medicines for rare diseases in 2014 ranged between €0.2 and €31.9/inhabitant.Conclusions
Patient access to medicines for rare diseases varies largely across Europe. Patients in Germany, Scandinavian countries, Switzerland, France, and the United Kingdom can access larger numbers of medicines in shorter time. 相似文献18.
Background
Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function.Objectives
To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function.Methods
A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results.Results
Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings.Conclusions
Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment. 相似文献19.
Edward C.F. Wilson Juliet A. Usher-Smith Jon Emery Pippa G. Corrie Fiona M. Walter 《Value in health》2018,21(6):669-676
Background
Expert elicitation is required to inform decision making when relevant “better quality” data either do not exist or cannot be collected. An example of this is to inform decisions as to whether to screen for melanoma. A key input is the counterfactual, in this case the natural history of melanoma in patients who are undiagnosed and hence untreated.Objectives
To elicit expert opinion on the probability of disease progression in patients with melanoma that is undetected and hence untreated.Methods
A bespoke webinar-based expert elicitation protocol was administered to 14 participants in the United Kingdom, Australia, and New Zealand, comprising 12 multinomial questions on the probability of progression from one disease stage to another in the absence of treatment. A modified Connor-Mosimann distribution was fitted to individual responses to each question. Individual responses were pooled using a Monte-Carlo simulation approach. Participants were asked to provide feedback on the process.Results
A pooled modified Connor-Mosimann distribution was successfully derived from participants’ responses. Feedback from participants was generally positive, with 86% willing to take part in such an exercise again. Nevertheless, only 57% of participants felt that this was a valid approach to determine the risk of disease progression. Qualitative feedback reflected some understanding of the need to rely on expert elicitation in the absence of “hard” data.Conclusions
We successfully elicited and pooled the beliefs of experts in melanoma regarding the probability of disease progression in a format suitable for inclusion in a decision-analytic model. 相似文献20.
Elizabeth A. Griffiths Richard Macaulay Nirma K. Vadlamudi Jasim Uddin Ebony R. Samuels 《Value in health》2017,20(10):1245-1251