Patient-powered research networks: building capacity for conducting patient-centered clinical outcomes research.

The Patient-Centered Outcomes Research Institute (PCORI) recently launched PCORnet to establish a single inter-operable multicenter data research network that will support observational research and randomized clinical trials. This paper provides an overview of the patient-powered research networks (PPRNs), networks of patient organizations focused on a particular health condition that are interested in sharing health information and engaging in research. PPRNs will build on their foundation of trust within the patient communities and draw on their expertise, working with participants to identify true patient-centered outcomes and direct a patient-centered research agenda. The PPRNs will overcome common challenges including enrolling a diverse and representative patient population; engaging patients in governance; designing the data infrastructure; sharing data securely while protecting privacy; prioritizing research questions; scaling small networks into a larger network; and identifying pathways to sustainability. PCORnet will be the first distributed research network to bring PCOR to national scale

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

Using indirect evidence to determine the comparative effectiveness of prescription drugs: do benefits outweigh risks?

Health care decision-makers rarely have the appropriate evidence to evaluate the comparative clinical effectiveness of new and existing prescription drugs. In the absence of head-to-head trials comparing all available drugs, indirect comparisons of randomized trials can offer a valuable approach to investigators evaluating the comparative effect of multiple drugs. Indirect comparisons, particularly methods that allow the combination of direct and indirect evidence obtained from randomized trials, can assist in identifying which of multiple prescription drugs works better than others. In this article, we discuss the benefits and risks of using indirect evidence and make the case in favor of its wider use within the comparative effectiveness research efforts in the US. We further argue that the use of indirect comparisons should be pursued in cases where trials comparing the interventions of interest are available

National approaches to comparative effectiveness research

Recently, Comparative Effectiveness Research (CER) has received considerable attention in the United States. This type of research has been underway in various settings for some time – most commonly as inputs to formal health technology assessment processes used to determine the medical, social, economic, and ethical issues related to the use of a health technology. As it is conceived in the United States, CER goes beyond health technology assessment, and encompasses research efforts that aim to encourage healthcare decision-making to be increasingly based on comparative evidence on clinical and humanistic patient-centred outcomes at both the individual and population levels. This chapter reviews the national approaches to conducting CER across various European countries in addition to Australia and Canada. Adopting an emerging United States-centric definition of CER, which focuses on clinical evidence..

The impact of increasing neurological disability of multiple sclerosis on health utilities: a systematic review of the literature

Background: Multiple sclerosis (MS) is a debilitating disease, accompanied by neurological symptoms of varying severity. Utilities are a key summary index measure used in assessing health-related quality of life in individuals with MS. Objectives: To provide a systematic review of the literature on utilities of relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients and to review changes in utilities associated with the increasing neurological disability of different stages of MS, as measured by the Expanded Disability Status Scale (EDSS). Methods: Employing pre-defined search terms and inclusion/exclusion criteria, systematic searches of the literature were conducted in EMBASE, MEDLINE, PsycINFO, the Health Economic Evaluation Database (HEED), and the NHS Economic Evaluations Database (NHS/EED). Proceedings for the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), the European Society for Treatment and Research in MS (ECTRIMS), the American Society for Treatment and Research in MS (ACTRIMS), and the Latin American Society for Treatment and Research in MS (LACTRIMS) were reviewed in addition to the UK National Institute for Health and Clinical Excellence website and the table of contents of PharmacoEconomics and Value in Health. Results: This review identified 18 studies reporting utilities associated with health states of MS. Utilities ranged from 0.80 to 0.92 for patients with an EDSS score of 1, from 0.49 to 0.71 for patients with an EDSS score of 3, from 0.39 to 0.54 for patients with an EDSS score of 6.5, and from –0.19 to 0.1 for patients with an EDSS score of 9. Limitations: Several of the studies reviewed relied on data from patient organizations, which may not be fully representative of the general patient populations. Additionally, the majority of the studies relied on retrospective data collection. Conclusions: Utilities decrease substantially with increasing neurological disability. Cross-country differences are minimal with utility scores following a similar pattern across countries for patients at similar disease severity levels. This consistency in findings is noteworthy, as there is a reliable evidence base for selecting utility values for economic evaluation analyses. However, more research is needed to explore potential differences in utilities between RRMS and SPMS patient

Does the Funding Source Influence the Results in Economic Evaluations?: A Case Study in Bisphosphonates for the Treatment of Osteoporosis

Background: Research sponsored by the pharmaceutical industry is often assumed to be more likely to report favourable cost-effectiveness results. Objective: To determine whether there was a relationship between the source of funding and the reporting of positive results. Methods: 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 &dollar;US20 000, &dollar;US50 000 and &dollar;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. Results: 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 &dollar;US20 000 and &dollar;US50 000. However, industry-sponsored studies were more likely to report ICERs below &dollar;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 &dollar;US20 000 and &dollar;US50 000 than studies of lower methodological quality (scores <4). Methodological quality was not significantly different between studies reporting ICERs under &dollar;US100 000. Conclusions: 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 &dollar;US20 000 and &dollar;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 &dollar;US20 000 and &dollar;US50 000 per QALY. Further research should explore this finding.Bisphosphonates, therapeutic use, Cost-utility, Osteoporosis, treatment

Economic Burden of Multiple Sclerosis: A Systematic Review of the Literature

Multiple sclerosis (MS) is a disease of the CNS, typically striking adults during the primary productive time of their life. The symptoms of MS can restrict the individual's physical activity and income-earning ability, resulting in a major financial burden on the patient, family, health system and society. This systematic literature review was conducted to document the economic burden of MS. Employing pre-defined search terms and inclusion/exclusion criteria, systematic searches were conducted in MEDLINE, EMBASE, PsycINFO, the Health Economic Evaluations Database (HEED), the NHS Economic Evaluation Database (EED) and the UK National Institute for Health and Clinical Excellence (NICE) website as well as conference abstracts. We identified 29 cost-of-illness studies that met the a priori inclusion criteria. The cost categories responsible for the majority of costs associated with MS varied across countries. There was a significant increase in costs associated with an increase in disease severity as measured by the Kurtzke Expanded Disability Status Scale (EDSS) score. The increase in magnitude was coupled with changes in the distribution of costs; although direct medical costs were important contributors in earlier stages of disease, they were outweighed by indirect costs in later stages, mainly due to relapses and productivity losses. Considering the increased costs associated with relapse occurrence and increasing disease severity, pharmaceutical or non-pharmaceutical interventions aimed at delaying the progression of disease may help to reduce the economic burden of MS.Cost-of-illness, Multiple-sclerosis, treatment

Comparative effects of statins on major cerebrovascular events: a multiple-treatments meta-analysis of placebo-controlled and active-comparator trials

Statins are important in the prevention of major cerebrovascular events. Whether, and the extent to which, individual statins differ in terms of their effect on these outcomes has not been studied. The aimof this review was to evaluate the comparative effects of individual statins on major cerebrovascular events. We systematically reviewed 61 trials including 187 038 individuals with, or at risk of developing, cardiovascular disease. We performed pair-wise and multipletreatments meta-analyses for major cerebrovascular events, in addition to fatal and non-fatal strokes separately. Across all populations, statins were significantly more effective than control in reducing major cerebrovascular events [odds ratio (OR): 0.82, 95% CI: 0.77, 0.87], with no differences among individual statins. Statins were also effective in patients with established cardiovascular disease (OR: 0.83, 95% CI: 0.75, 0.91) and in those without (OR: 0.80, 95% CI: 0.71, 0.91). Considering individual statins, significant risk reductions were achieved with atorvastatin (OR: 0.74, 95%CI: 0.63, 0.85), pravastatin (OR: 0.86, 95% CI: 0.76, 0.97) and simvastatin (OR: 0.75, 95% CI: 0.62, 0.88) as compared with control on major cerebrovascular events across all populations. Statins led to significant reductions in the risk of non-fatal strokes (OR: 0.77, 95% CI: 0.71, 0.85) but not of fatal strokes (OR: 0.96, 95% CI: 0.80, 1.15). Findings were not sensitive to dose differentials of individual statins across the trials. No significant heterogeneity or inconsistency was detected. Statins significantly reduce the incidence of major cerebrovascular events as compared with control. Our analysis provided evidence to confirm the class effect of statins in preventing major cerebrovascular events. © The Author 2013. Published by Oxford University Press on behalf of the Association of Physicians

Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials

Aims: The extent to which individual statins vary in terms of their impact on serum lipid levels has been studied mainly on the basis of placebo-controlled trials. Our objective was to review and quantify the dose-comparative effects of different statins on serum lipid levels using both placebo- and active-comparator trials. Methods: We systematically reviewed randomized trials evaluating different statins in participants with, or at risk of developing, cardiovascular disease. We performed random-effects Bayesian network meta-analyses to quantify the the relative potency of individual statins across all possible dose combinations using both direct and indirect evidence. Dosecomparative effects were determined by estimating the mean change from baseline in serum lipids as compared to control treatment. (systematic review registration: PROSPERO 2011:CRD42011001470). Results: We included 181 placebo-controlled and active-comparator trials including 256,827 individuals. There were 83 two-armed placebo-controlled trials and the remaining 98 were two- or multi-armed active-comparator trials. All statins reduced serum LDL and total cholesterol levels: higher doses resulted in higher reductions in pretreatment LDL and total cholesterol concentrations. In absolute terms, all statins significantly reduced LDL cholesterol levels as compared to control treatment from average baseline levels of approximately 150 mg/dl, except for fluvastatin at ≤20 mg/day and lovastatin at ≤10 mg/day. Atorvastatin, rosuvastatin, and simvastatin were broadly equivalent in terms of their LDL cholesterol-lowering effects. Dose-comparative effects of indivudual statins were not different between those with and without coronary heart disease at baseline. According to meta-regression analyses, LDL cholesterol-lowering effects of individual statins were not impacted by differences across trials in terms of baseline mean age and proportion of women as trial participants. Pretreatment LDL cholesterol concentrations had a marginally statistically significant effect on LDL cholesterol change from baseline. Mean differences from baseline in HDL cholesterol as compared to control treatment was not significant for any statin-dose combination. Conclusions: The findings of this comprehensive review provide supporting evidence for the doseresponse relationship of statins in reducing LDL and total cholesterol. The LDL cholesterol-reducing effects of some statins appear less pronounced than the findings of previous meta-analyses, which is particularly the case for the high-dose formulations of atorvastatin and rosuvastatin. The most consistent evidence for a combined reduction in both LDL and total cholesterol was achieved with atorvastatin at >40 mg/day, rosuvastatin at >10 mg/day, and simvastatin at >40 mg/day, which appear equivalent in terms of their LDL and total cholesterol-reducing effect