Improving healthcare efficiency The International Society for Pharmacoeconomics and Outcomes Research 17th Annual International Meeting, Washington, DC, USA, 2–6 June 2012. The International Society for Pharmacoeconomics and Outcomes Research recently sponsored the 17th Annual International Meeting. The meeting represented researchers and practitioners including pharmacists, physicians, economists and other professionals involved in pharmacoeconomic analysis and health outcomes assessment, as well as users of this information in healthcare decisions such as in hospitals, managed care and pharmacy benefit design organizations personnel.
The global healthcare industry operates in an increasingly constrained environment. Despite the growing acceptance of comparative effectiveness research (CER) by multiple industry stakeholders, scrutiny by regulators and payers on the questions of benefit–risk and value persists in the healthcare community . The move towards more extensive use of CER and greater utilization of preventive care provides an environment in which evidence will become more important to healthcare decisionmakers . As such, the methods of CER continue to evolve to realize the full potential of such research as countries and international organizations strive to improve healthcare efficiency. Central to the development of innovative methodologies are health economics and outcomes research (HEOR) professionals. Techniques that can assess and interpret a diverse body of evidence consisting of prospective randomized trials (including pragmatic trials) and observational research using data obtained in the course of regular practice are being assessed and validated by HEOR researchers. In response, medical journals are incorporating rigorous approaches, including but not limited to peer review by independent experts, to assess the potential limitations inherent in such research, such as missing data, incomplete follow-up, unmeasured biases (confounding factors) and selective reporting of results . The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 17th Annual International Meeting took place at an opportune time to address many of these issues. The content of the meeting included an overview of the CER/healthcare efficiency environment, innovative research methodologies, the communication and translation of the research to end users and a glimpse into the future.
Mitch DeKoven*1, Prina Donga1, Julia Powers1, Katharine Coyle1 & Victoria Divino1 Health Economics and Outcomes Research, 1725 Duke Street, Suite 510, Alexandria, VA 22314, USA *Author for correspondence: [email protected]
Comparative effectiveness & healthcare efficiency: an overview
It is well recognized that any form of healthcare reform will include some components of cost–effectiveness and delivery efficiencies. Given the recent US Supreme Court ruling upholding most of the provisions of the US Patient Protection and Affordable Care Act (ACA), the conference’s second plenary session (moderated by Susan Dentzer, Editor-in-Chief, Health Affairs) entitled ‘Health Reform in the US: Better Health, Better Care, Lower Cost’ was particularly timely. The session provided insight into how the ACA is working to improve health outcomes in the USA in a more efficient way and at a lower cost. As there are disparate rates of chronic disease in the USA, which has reduced life expectancy while increasing costs for payers and families, the ACA aims to control these costs while expanding coverage to the uninsured and implement specific health promotion and prevention
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initiatives. One such example is the Maryland Health Benefit Exchange, which includes improvements in information technology and targeted recommendations (e.g., continuity of care, risk mitigation and a marketing plan). Several other ISPOR presentations further emphasized how essential efficiencies across all spectrums of healthcare can be, from biopharmaceutical discovery to generating comparative research through to individualized care and the social value of that care. Andy Wilson (Brandeis University, MA, USA) and Peter Neumann (Tufts Center for the Evaluation of Value and Risk in Health, MA, USA) led a discussion highlighting both the growth in available biopharmaceuticals and the challenge of balancing costs and true value. Their research concluded that the growing presence of biopharmaceuticals in cost-utility literature demonstrates many of these new and often very expensive products provide value for money when measured with cost–effectiveness ratios for other selected interventions (e.g., conventional pharma, immunizations, medical devices as well as other medical and surgical procedures). Kristijian Kahler (Novartis, Basel, Switzerland) presented a manufacturer-based HEOR perspective on recognizing the need to conduct the right CER studies early in clinical development by using alternative study designs to improve efficiency. These include large simple trials and cluster randomization trials in addition to disease registries that roll-over to product registries post-approval. These data can then be used to quickly generate real-world evidence, provide internal resources and infrastructure, such as administrative and clinical databases, and can be analyzed using high-powered computing applications to generate credible, peer-reviewed and transparent research under strict guidelines. Another panel moderated by researchers from the University of York (York, UK; Manuel A Espinoza, Karl Claxton, Andrea Manca and Mark Sculpher) presented a UK viewpoint on alternative decision-making approaches and the value of heterogeneity in the era of individualized care. The panel recognized that, while individualized care has become a central policy issue around the globe, implementation of unrestricted choices must be balanced with forgone net health benefits to the rest of society, which is essential to ensure that healthcare resources are used in the most efficient way possible to benefit both the individual and society as a whole.
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Innovative research methodologies
In the current and future healthcare environment, patient-reported outcomes (PROs) are increasingly becoming standard end points in randomized clinical trials (RCTs), in addition to clinical/economic end points. Consequently, the momentum of real-world evidence is resulting in the development of standardized tools and methodologies to aid researchers and decision-makers. One such example is a CER initiative between the Academy of Managed Care Pharmacy, ISPOR and the National Pharmaceutical Council (NPC), which has been launched to enhance the usefulness of CER to improve patient health outcomes. The first part of this initiative is to develop a set of consistent measurement tools for assessing the credibility and relevance of nonexperimental studies for healthcare decision-makers. Out of the four types of nonexperimental studies identified (prospective observational, retrospective observational, modeling and network meta-analysis), assessment tools have been proposed for prospective observational and network meta-analysis studies by ISPOR task forces. The proposed tool for prospective observational studies will consist of 25–30 items covering dimensions of credibility (eight domains) and relevance (two domains) and will be available to use at different levels including checklist (yes/no; level one), scorecard (level two) and annotated scorecard (level three). The proposed tool for network metaanalysis studies will consist of 27 items divided into three sections: relevance for the decision problem (five questions); assessment of adequacy of methodology and quality (14 questions); and completeness of reporting (eight questions). Quintiles Outcome (MA, USA) and the NPC have collaborated to develop a tool called The Good ReseArch for Comparative Effectiveness (GRACE) checklist. It is designed to assess observational studies on comparative effectiveness in terms of quality and usefulness of decision-making, having been developed through contributions from global academic, government and private sectors. The checklist consists of 12 questions that evaluate population, intervention, comparator, outcomes, covariates and analysis. However, scoring algorithms have not yet been developed. The PRO Mixed Modes Task Force was developed to address the use of multiple modes of data collection in clinical trials. With an increase in RCT PRO end points, multiple modes can
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reduce missing data and allow for larger sample sizes. Recommendations on using multiple modes included selecting the appropriate modes for the trial, performing a ‘faithful migration’ or developing alternative modes of data collection (while ensuring that it captures the same data), evaluating equivalence between the modes (qualitative and quantitative) and implementing the modes into the trial. Additional methodologies related to PROs focused on comparing the value of classical test theory, item response theory and Rasch measurement theory in the development of instruments. An existing instrument was evaluated using the three theories and comparisons were presented. Similar comparisons can be considered in cases where the original development methods are different from the interpretation needs or when required by regulatory bodies. Finally, Mike Paulden of the University of Toronto (Toronto, Canada) shared a new advancement on the gaps of using incremental cost–effectiveness ratios and willingness-to-pay thresholds in cost–effectiveness analysis studies. To compare multiple strategies on the cost–effectiveness plane, determine the magnitude of cost–effectiveness of each strategy compared with others and be able to rank the strategies, plotting indifference curves using the net benefit approach was proposed instead of the traditional method of calculating incremental cost–effectiveness ratios and plotting cost–effectiveness acceptability curves. Communicating & translating CER research
While the importance of the research methods described earlier cannot be understated, efforts may be lost if they cannot be disseminated in language that is understandable to formulary and policy decision-makers. As such, transparency emerged as a key theme at the conference. Shelby D Reed (Duke Clinical Research Institute, NC, USA), Scott Ramsey (University of Washington, WA, USA), Michael Iskedjian (Université de Montréal, QC, Canada) and John O’Donnell (Bristol-Myers Sqibb Co., NJ, USA) led a healthcare policy development workshop and discussed the nuts and bolts of presenting research to healthcare authorities and emphasized the importance of communicating and disseminating research findings. Highlights included a call for increased transparency about research methods and modeling assumptions as well as a need for accurate and concise summaries of studies supporting new pharmaceutical
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products. One of the conference’s issue panels included a discussion of CER specific to oncology. Since there are limited existing principles guiding CER in this therapeutic area, Sean Sullivan (University of Washington, WA, USA), Art Small (Genentech, CA, USA) and Jennifer Malin (WellPoint, IN, USA) reported the guidelines developed by a broader group. Key messages from the guidelines conveyed the importance of method transparency, including selecting clinically meaningful end points and comparators, minimizing bias and ensuring that conclusions be supported by evidence. Similarly, another issue panel discussed the use of manufacturer-generated budget impact models for use by decision-makers and concluded that quality and relevance of inputs and flexibility of the model through customization are most important. Eleanor Perfetto (Pfizer, Inc., NY, USA) led a third issue panel around a discussion of patient-centered outcomes research and addressed the need to make patient engagement useful beyond checking the box; Melissa McPheeters (Vanderbilt Evidence-Based Practice Center, TN, USA) reiterated that patient engagement is valuable and improves the understanding of issues and what is most important to patients. While the Patient-Centered Outcomes Research Institute (PCORI, Washington, DC, USA) has significant budget allocated to dissemination and infrastructure, questions remain about the best methods. One research team, led by Teresa Gibson (Thomson Reuters, NY, USA), and another, led by Justin Timbie (R AND Corporation, CA, USA), presented findings evaluating the effect of CER studies on real-world current practice. A variety of CER studies were examined and the results were mixed; in some cases practices were changing before the release of CER, while in others, practices changed following the CER, and yet in others no changes were identified following CER. The researchers concluded that change following CER may be slow and requires accumulation of high-quality evidence, but that opportunities exist to improve the translation of CER into clinical practice. Healthcare efficiency: moving forward
Should the US FDA place more emphasis on evidence of comparative effectiveness for new drugs (i.e., does a new drug work better than an available drug[s] rather than does a new drug work?). Sean Tunis (Center for Medical Technology Policy, MD, USA) proposed that encouraging
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premarket CER regulatory reviews would improve the efficiency of drug development and overall public health. In addition, specific recommendations regarding the Institute of Medicine’s features of CER were highlighted – preapproved trials should provide more information on: results in patients with common comorbidities to the primary condition being treated; comparisons on risks and benefits of alternative treatments; measurements of outcomes that are most relevant to patients and are used by clinicians in patient management; and follow-up of more clinically relevant duration. Early advice on CER and clinical development may be obtained from payer advisory boards and health technology assessment (HTA) groups (mostly ex-USA and in Europe). The Green Park Collaborative is an international pilot initiative that is exploring the scientific feasibility of developing guidance documents with recommendations on the design of clinical studies to meet the needs of payers and HTA organizations. The collaborative seeks to produce prototype ‘evidence guidance documents’ that will provide therapeutic area-specific trial design recommendations, as well as general methodological advice that can be applied across therapeutic areas. Their guidance is intended to reduce the uncertainty regarding the evidentiary preferences of HTA and coverage bodies, improve the relevance of clinical research and improve patient access to useful innovations. Their efforts will be informed by existing regulatory guidance and current best practices in research methods. A plenary session moderated by Lou Garrison (University of Washington School of Pharmacy, WA, USA) and Adrian Towse (Office of Health Economics, London, UK) discussed performance-based risk-sharing arrangements (PBRSAs). The PRBSA Task Force has been established with the objective to set the standards that should be applied to a ‘good practice’ PRBSA, encompassing the design, implementation and evaluation of such arrangements, and to provide practical recommendations for the development and application of state-of-the-art methods to be used in their design, implementation and evaluation. There is growing interest among payers and manufacturers for payment arrangements/schemes that involve a ‘pay-forperformance’ or ‘risk-sharing’ element, in which a product’s performance is tracked in a defined patient population over a specified period of time and the price, reimbursement and/or revenue is tied by formula to the evidence of the outcomes
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achieved. PBRSAs are useful in such cases that there is uncertainty that needs to be reduced. Data collection is typically initiated during the time period following regulatory approval and is intended to provide evidence to address the relevant uncertainty. There are substantial barriers to forming PRBSAs, including potentially high costs of negotiation, evaluation and monitoring to obtain evidence. PBRSAs may become more prominent with a better understanding of biomarkers and pathways, with growing research into therapeutic areas where final outcomes take a relatively long time to observe, and in personalized healthcare. Marc Berger (OptumInsight, MN, USA) and S Tunis discussed the use of pragmatic Phase IIIb trials (defined as studies initiated prior to regulatory approval but not one of the pivotal trials included in regulatory submission) as an opportunity to accelerate the development of CER. Pragmatic Phase IIIb trials may more quickly close the gap between the different evidence standards required by US regulators and HTA authorities. Pragmatic trials address the question as to the preference of two treatments. Design of pragmatic clinical trials includes a relevant comparator, which is usual care or the most common alterative, naturalistic conditions, including routine management and monitoring following usual care, and more diverse treatment settings with a broader inclusion/exclusion criteria resulting in a more heterogeneous population. Clinical end points are more meaningful and assess true outcomes such as morbidity, mortality and quality of life. Criticisms regarding pragmatic clinical trials include high rates of loss to follow-up, nonadherence, unblended treatment and patient self-assessment, sacrifice of internal validity to achieve generalizability and the requirement of large sample sizes. However, much of this criticism is a fundamental problem in real-world healthcare (e.g., if patients are nonadherent); thus, this problem must be permitted to occur within the setting of the trial. Financial & competing interests disclosure All authors are employed by IMS Health. No products from this company are reviewed in this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
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