A National Hepatitis C Elimination Program in the United States: A Historic Opportunity.

This Viewpoint introduces a proposed 5-year program from the Biden-Harris administration that would use direct-acting antivirals to eliminate hepatitis C in the United States.

Patient-powered research networks aim to improve patient care and health research.

The era of big data, loosely defined as the development and analysis of large or complex data sets, brings new opportunities to empower patients and their families to generate, collect, and use their health information for both clinical and research purposes. In 2013 the Patient-Centered Outcomes Research Institute launched a large national research network, PCORnet, that includes both clinical and patient-powered research networks. This article describes these networks, their potential uses, and the challenges they face. The networks are engaging patients, family members, and caregivers in four key ways: contributing data securely, with privacy protected; including diverse and representative groups of patients in research; prioritizing research questions, participating in research, and disseminating results; and participating in the leadership and governance of patient-powered research networks. If technical, regulatory, and organizational challenges can be overcome, PCORnet will allow research to be conducted more efficiently and cost-effectively and results to be disseminated quickly back to patients, clinicians, and delivery systems to improve patient health.

Engaging patients and stakeholders in research proposal review: the patient-centered outcomes research institute.

The inaugural round of merit review for the Patient-Centered Outcomes Research Institute (PCORI) in November 2012 included patients and other stakeholders, as well as scientists. This article examines relationships among scores of the 3 reviewer types, changes in scoring after in-person discussion, and the effect of inclusion of patient and stakeholder reviewers on the review process. In the first phase, 363 scientists scored 480 applications. In the second phase, 59 scientists, 21 patients, and 31 stakeholders provided a "prediscussion" score and a final "postdiscussion" score after an in-person meeting for applications. Bland-Altman plots were used to characterize levels of agreement among and within reviewer types before and after discussion. Before discussion, there was little agreement among average scores given by the 4 lead scientific reviewers and patient and stakeholder reviewers. After discussion, the 4 primary reviewers showed mild convergence in their scores, and the 21-member panel came to a much stronger agreement. Of the 25 awards with the best (and lowest) scores after phase 2, only 13 had ranked in the top 25 after the phase 1 review by scientists. Five percent of the 480 proposals submitted were funded. The authors conclude that patient and stakeholder reviewers brought different perspectives to the review process but that in-person discussion led to closer agreement among reviewer types. It is not yet known whether these conclusions are generalizable to future rounds of peer review. Future work would benefit from additional data collection for evaluation purposes and from long-term evaluation of the effect on the funded research.

Launching PCORnet, a national patient-centered clinical research network.

The Patient-Centered Outcomes Research Institute (PCORI) has launched PCORnet, a major initiative to support an effective, sustainable national research infrastructure that will advance the use of electronic health data in comparative effectiveness research (CER) and other types of research. In December 2013, PCORI's board of governors funded 11 clinical data research networks (CDRNs) and 18 patient-powered research networks (PPRNs) for a period of 18 months. CDRNs are based on the electronic health records and other electronic sources of very large populations receiving healthcare within integrated or networked delivery systems. PPRNs are built primarily by communities of motivated patients, forming partnerships with researchers. These patients intend to participate in clinical research, by generating questions, sharing data, volunteering for interventional trials, and interpreting and disseminating results. Rapidly building a new national resource to facilitate a large-scale, patient-centered CER is associated with a number of technical, regulatory, and organizational challenges, which are described here.

A systematic review of adherence, treatment satisfaction and costs, in fixed-dose combination regimens in type 2 diabetes.

OBJECTIVE: Oral antidiabetics have comparable safety and efficacy when used as fixed-dose combination therapies (FDCT) or loose-pill combination therapies (LPCT) for patients with T2DM. To evaluate alternative outcomes to safety and efficacy with FDCT, a systematic review of literature was conducted. METHODS: Searches of Medline/Embase databases from 1998 to 2009 used predefined terms: 'fixed-dose combination', 'loose-dose combination' and 'diabetes'. Abstracts were reviewed from ISPOR, ADA, and EASD meetings (1998-2009). T2DM studies reporting adherence, patient-reported outcomes, costs, resource use or cost effectiveness were included. RESULTS: Seventeen studies met the search criteria. Seven studies reported adherence. Adherence was 10-13% higher for FDCT than LPCT in patients starting combination therapy. Adherence decreased 1.5% and 10.0% when switching from monotherapy to combination therapy for FDCT and LPCT respectively (p < 0.001). Switching to FDCT increased adherence 3.5%-12.4%, while remaining on LPCT changed adherence -1.5% to 5.0% (p < 0.005). For patients newly initiating OAD medication, one study found no adherence advantage for FDCT compared with monotherapy or LPCT. Five RCTs reported treatment satisfaction. Four publications reported patients preferred FDCT using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). One publication reported improved satisfaction for one DTSQ subscale. Five abstracts reported economic outcomes. Two abstracts determined patients on FDCT used fewer healthcare resources and had decreased direct monthly healthcare costs versus LPCT. Two cost-effectiveness analyses determined clinical benefits from clinical trials translate into cost savings and increased life expectancy. One budget impact model reported minimal budget impact. LIMITATIONS: (1) There was limited published literature identified in this review. (2) FDCT are oral medications; these findings may only be relevant to those individuals taking an oral antidiabetic therapy. (3) Publication and reporting biases may exist. CONCLUSIONS: The published literature suggested that T2DM patients treated with FDCT may have better adherence, improved satisfaction, and lower direct medical costs, compared to those treated with LPCT.

The critical role of observational evidence in comparative effectiveness research.

Although not the gold standard of clinical research, observational studies can play a central role as the nation's health care system embraces comparative effectiveness research. Investigators generally prefer randomized trials to observational studies because the former are less subject to bias. Randomized studies, however, often don't represent real-world patient populations, while observational studies can offer quicker results and the opportunity to investigate large numbers of interventions and outcomes among diverse populations--sometimes at lower costs. But some decisions based on observational studies have turned out to be wrong. We recommend that researchers adopt a "body of evidence" approach that includes both randomized and observational evidence.

Does the funding source influence the results in economic evaluations? A case study in bisphosphonates for the treatment of osteoporosis.

Research sponsored by the pharmaceutical industry is often assumed to be more likely to report favourable cost-effectiveness results. To determine whether there was a relationship between the source of funding and the reporting of positive results. We conducted a systematic review of the literature to identify economic evaluations of bisphosphonates for the treatment of osteoporosis. We extracted the source of funding, region of study, the journal name and impact factor, and all reported incremental cost-effectiveness ratios (ICERs). We identified which ICERs were under the thresholds of $US20 000, $US50 000 and $US100 000 per QALY. A quality score between 0 and 7 was also given to each of the studies. We used generalized estimating equations for the analysis. The systematic review yielded 532 potential abstracts; 17 of these met our final eligibility criteria. Ten studies (59%) were funded by non-industry sources. A total of 571 ICERs were analysed. There was no significant difference between the number of industry- and non-industry-funded studies reporting ICERs below the thresholds of $US20 000 and $US50 000. However, industry-sponsored studies were more likely to report ICERs below $US100 000 (odds ratio = 4.69, 95% CI 1.77, 12.43). Studies of higher methodological quality (scoring >4.5 of 7) were less likely to report ICERs below $US20 000 and $US50 000 than studies of lower methodological quality (scores <4). Methodological quality was not significantly different between studies reporting ICERs under $US100 000. In this relatively small sample of studies of bisphosphonates, the funding source (industry vs non-industry) did not seem to significantly affect the reporting of ICERs below the $US20 000 and $US50 000 thresholds. We hypothesize that methodological quality might be a more significant factor than the source of funding in differentiating which studies are likely to report favourable ICERs, with the higher-quality studies significantly less likely to report ICERs below $US20 000 and $US50 000 per QALY. Further research should explore this finding.

The cost effectiveness of bisphosphonates for the prevention and treatment of osteoporosis: a structured review of the literature.

Osteoporotic fragility fractures constitute a significant public health concern. The lifetime risk of any osteoporotic fracture is very high (40-50% in women and 13-22% in men). Fractures are associated with significant mortality and morbidity and represent a substantial economic burden to society. Bisphosphonates (alendronate, etidronate, risedronate and ibandronate) are indicated for the treatment and prevention of osteoporosis but are costly compared with other treatments, such as vitamin D and calcium. Our search identified 23 studies evaluating the cost effectiveness of bisphosphonate therapy for the treatment and prevention of fragility fractures; these studies were from five geographical areas and employed a variety of comparators and assumptions. We identified 11 studies investigating bisphosphonates in women with low bone mineral density (BMD) [T-score >2.5 standard deviations {SDs} below normal {mean} peak values for young adults] and previous fractures, five studies investigating bisphosphonates in women with low BMD and no previous fracture, one study of bisphosphonates in women with osteopenia, five studies involving screening and two studies of bisphosphonates in special populations (women initiating corticosteroid treatment and men). In women with low BMD and previous fractures, bisphosphonate therapy was most cost effective in populations aged > or =70 years and was unlikely to be cost effective in populations aged < or =50 years. There was uncertainty concerning the cost effectiveness of bisphosphonates in such populations aged 60-69 years. In women with low BMD without previous fractures, treatment with alendronate or risedronate appeared to be cost effective across countries (UK, US, Denmark), but there was some uncertainty about the cost effectiveness of etidronate in patients in the highest age groups. Identifying risk factors for fractures through means such as spine radiographs to detect vertebral deformities improves the cost effectiveness of treatment. In women with osteopenia, alendronate therapy may be cost effective in women with a T-score of -2.4SD in the US. Screening for low BMD and treatment with alendronate or etidronate appears to be cost effective in postmenopausal women in general and in women with rheumatoid arthritis initiating corticosteroid therapy. Alendronate therapy without screening was also shown to be potentially cost effective in certain at-risk male populations, as well as in women initiating corticosteroid therapy after the age of 40 years. Decision makers in the US, UK and Sweden should consider funding the use of bisphosphonates for the prevention and treatment of osteoporosis in women aged >70 years, particularly if they have other risk factors for fracture. Further studies are required to make more definitive conclusions in other countries and patient populations. Screening strategies for low BMD followed by bisphosphonate treatment should also be considered in the general female population aged >65 years in the UK and US and in patients with rheumatoid arthritis initiating corticosteroid therapy.

Setting priorities for research: a practical application of 'payback' and expected value of information.

BACKGROUND: Setting priorities for research using economic in addition to scientific criteria can ensure that resources are spent efficiently and equitably. OBJECTIVE: This study applies two priority setting methods 'payback' and expected value of information (EVI) to two research areas (osteoporosis and pressure ulcers) and where appropriate to four clinical trials: the Record Trial, the Vitamin D and Calcium Trial and the Hip Protector Trial (osteoporosis), and the Pressure Trial (wound care). METHODS: Two decision-analytic models were developed. For 'payback', the PATHS model was used to estimate the expected net benefits of conducting the four clinical trials. An EVI framework was applied to estimate the cost-effectiveness of conducting further research in the two disease areas investigated. RESULTS: The application of 'payback' suggests that the Record Trial and the Vitamin D and Calcium Trial would be cost-effective. The Hip Protector and the Pressure Ulcer Trial are cost-effective under certain assumptions concerning the likelihood of obtaining positive, negative or inconclusive results. The EVI method suggests that research would be potentially cost-effective in these areas in the populations considered. CONCLUSION: EVI provides strategic information for setting priorities for research between disease areas and study populations. 'Payback' provides information on the cost-effectiveness of specific research designs. However, further work in this area, particularly concerning the issue of implementation of research, is required.

Review of the economic and quality-of-life burden of cervical human papillomavirus disease.

OBJECTIVE: The purpose of this study was to conduct a systematic literature review on the economic burden and health-related quality-of-life impact of cervical human papillomavirus disease. STUDY DESIGN: A systematic review of cost-of-illness studies and health-related quality-of-life studies was conducted. PubMed, Embase, and PsycINFO databases were searched with the use of predefined terms. RESULTS: Nine economic and 24 quality-of-life studies were identified. The annual health care costs of human papillomavirus-related conditions in the United States range from 2.25-4.6 billion dollars (2005 US dollars). The burden of human papillomavirus is second only to human immunodeficiency virus among sexually transmitted diseases. Health-related quality-of-life areas that are impacted substantially by human papillomavirus include emotional, social, and sexual functioning. CONCLUSION: The economic and quality-of-life burden of cervical human papillomavirus disease is significant and highlights the need for treatment and prevention options for this condition.

Economic outcomes associated with atypical antipsychotics in bipolar disorder: a systematic review.

OBJECTIVE: Bipolar disorder is a serious condition that is costly to the health care system. Atypical antipsychotics are more expensive than conventional treatments. From a policy-making perspective, the additional cost must be justified by improved outcomes. The objective of this study was to conduct a systematic review to determine the relative costs and cost-effectiveness associated with atypical antipsychotics in bipolar disorder. DATA SOURCES: We conducted a systematic review of the literature in PubMed and EMBASE from January 1985 through October 2005, including published studies and conference proceedings. Databases were searched using predefined terms. STUDY SELECTION: Studies were included if they were claims data analyses, trial-based economic evaluations, or cost-effectiveness analyses using models. Data were extracted using predefined tables. DATA SYNTHESIS: Fourteen studies were identified. Seven were medical claims database analyses, 4 were trial-based economic evaluations, and 3 were cost-effectiveness models. Eight of these studies were conference proceedings. The studies did not provide sufficient information to determine any ranking of interventions in terms of least to most costly in overall resource consumption or in terms of their relative cost-effectiveness. Where comparable, results tended to be inconsistent. CONCLUSION: There is a scarcity of economic studies in this field. A reference case outlining how to address the complex interplay between effectiveness, safety, adherence, and quality of life and their impact on resource use and costs is needed to contribute to improving the treatment of patients with bipolar disorder while making the best use of scarce health resources.