Performance-based risk-sharing arrangements-good practices for design, implementation, and evaluation: report of the ISPOR good practices for performance-based risk-sharing arrangements task force.

There is a significant and growing interest among both payers and producers of medical products for agreements that involve a "pay-for-performance" or "risk-sharing" element. These payment schemes-called "performance-based risk-sharing arrangements" (PBRSAs)-involve a plan by which the performance of the product is tracked in a defined patient population over a specified period of time and the amount or level of reimbursement is based on the health and cost outcomes achieved. There has always been considerable uncertainty at product launch about the ultimate real-world clinical and economic performance of new products, but this appears to have increased in recent years. PBRSAs represent one mechanism for reducing this uncertainty through greater investment in evidence collection while a technology is used within a health care system. The objective of this Task Force report was to set out the standards that should be applied to "good practices"-both research and operational-in the use of a PBRSA, encompassing questions around the desirability, design, implementation, and evaluation of such an arrangement. This report provides practical recommendations for the development and application of state-of-the-art methods to be used when considering, using, or reviewing PBRSAs. Key findings and recommendations include the following. Additional evidence collection is costly, and there are numerous barriers to establishing viable and cost-effective PBRSAs: negotiation, monitoring, and evaluation costs can be substantial. For good research practice in PBRSAs, it is critical to match the appropriate study and research design to the uncertainties being addressed. Good governance processes are also essential. The information generated as part of PBRSAs has public good aspects, bringing ethical and professional obligations, which need to be considered from a policy perspective. The societal desirability of a particular PBRSA is fundamentally an issue as to whether the cost of additional data collection is justified by the benefits of improved resource allocation decisions afforded by the additional evidence generated and the accompanying reduction in uncertainty. The ex post evaluation of a PBRSA should, however, be a multidimensional exercise that assesses many aspects, including not only the impact on long-term cost-effectiveness and whether appropriate evidence was generated but also process indicators, such as whether and how the evidence was used in coverage or reimbursement decisions, whether budget and time were appropriate, and whether the governance arrangements worked well. There is an important gap in the literature of structured ex post evaluation of PBRSAs. As an innovation in and of themselves, PBRSAs should also be evaluated from a long-run societal perspective in terms of their impact on dynamic efficiency (eliciting the optimal amount of innovation).

Public preferences for health states with schizophrenia and a mapping function to estimate utilities from positive and negative symptom scale scores.

BACKGROUND: Schizophrenia is a common severe syndrome with a highly variable pattern of symptoms. The medications used to treat this disorder are expensive and may cause severe adverse effects. Little is known about how the public perceives health outcomes in schizophrenia or the potential adverse effects of antipsychotic medication. This complicates the use of standard cost-effectiveness analysis to set priorities for health resource allocation. OBJECTIVE: In this study, we measured utility weights for a set of health states derived from Positive and Negative Symptom Scale (PANSS) scores, and a set of health states that included the presence of common adverse effects of medication, thus creating utility mapping function for clinical data. METHODS: We presented a convenience sample of members of a large commercial Internet survey panel with digital video materials portraying eight different patterns of schizophrenia with varying levels of positive, negative and cognitive symptoms, and five common adverse effects of antipsychotic medications. We then elicited their standard gamble (SG) and visual analog scale (VAS) ratings using iMPACT3 computer program, with an automated error repair feature, deliberately over-sampling minority ethnic groups in the panel. We censored subjects with uncorrected errors in ratings and estimated utilities for each state by re-weighting responses to match United States population demographics. SUBJECTS: 620 well-educated, ethnically diverse volunteers (54% Caucasian), who spanned a broad range of age groups and geographical regions of the US participated in this study. RESULTS: Because of evidence of bias in ratings, 175 (29%) subjects with internal inconsistencies in ratings were censored from estimates of mean population utilities. In the remaining 441 subjects, SG utilities, re-weighted to match US population demographic profiles, ranged from 0.88 for mild schizophrenia to 0.47 extremely severe schizophrenia. Variability in the types of symptoms exhibited (positive, negative or cognitive) was less important to participants than the overall severity of each state. Modest reductions in symptoms (for example, from severe to moderate or moderate to mild) were associated with relatively large changes in utility (0.12-0.19). Adverse effects decreased utilities for states by amounts ranging from 0.09 (pseudo-parkinsonism) to 0.05 (obesity). CONCLUSIONS: The public views schizophrenia is a very disabling syndrome and treatments that reduce symptoms produce important gains in utility, even if they do not induce a complete remission. Adverse effects significantly reduce utilities for states; therefore, cost-effectiveness analyses for this disorder should take adverse effects of treatment into consideration.

The heterogeneity of schizophrenia in disease states.

PREVIOUS PRESENTATION: Some of the contents of this paper have been previously presented at the 16th Annual Meeting of the International Society for Technology Assessment in Health Care June 20, 2000 in the Hague, Netherlands and at the 21st Annual Meeting of the Society for Medical Decision Making as a poster on October 3, 1999 in Reno, NV. BACKGROUND: Studies of schizophrenia treatment often oversimplify the array of health outcomes among patients. Our objective was to derive a set of disease states for schizophrenia using the Positive and Negative Symptom Assessment Scale (PANSS) that captured the heterogeneity of symptom responses. METHODS: Using data from a 1-year clinical trial that collected PANSS scores and costs on schizophrenic patients (N=663), we conducted a k-means cluster analyses on PANSS scores for items in five factor domains. Results of the cluster analysis were compared with a conceptual framework of disease states developed by an expert panel. Final disease states were defined by combining our conceptual framework with the empirical results. We tested its utility by examining the influence of disease state on treatment costs and prognosis. RESULTS: Analyses led to an eight-state framework with varying levels of positive, negative, and cognitive impairment. The extent of hostile/aggressive symptoms and mood disorders correlated with severity of disease states. Direct treatment costs for schizophrenia vary significantly across disease states (F=27.47, df=7, p<0.0001), and disease state at baseline was among the most important predictors of treatment outcomes. CONCLUSION: The disease states we describe offer a useful paradigm for understanding the links between symptom profiles and outcomes.

Medical and pharmacy coverage decision making at the population level.

Medicare is one of the largest health care payers in the United States. As a result, its decisions about coverage have profound implications for patient access to care. In this commentary, the authors describe how Medicare used evidence on heterogeneity of treatment effects to make population-based decisions on health care coverage for implantable cardiac defibrillators. This case is discussed in the context of the rapidly expanding availability of comparative effectiveness research. While there is a potential tension between population-based and patient-centered decision making, the expanded diversity of populations and settings included in comparative effectiveness research can provide useful information for making more discerning and informed policy and clinical decisions.

Recommendations for the design of Phase 3 pharmaceutical trials that are more informative for patients, clinicians, and payers.

BACKGROUND: Pharmaceutical pragmatic clinical trials (PCTs) are designed to provide the type of evidence that is desired by patients, clinicians and payers but too often missing from traditional regulatory trials. PURPOSE: This paper presents framework for designing pragmatic trials incorporating evidence desired by post-regulatory decision makers while remaining within acceptable standards for regulatory approval. METHODS: Following a stakeholder meeting convened in May of 2009 to identify gaps in information collected in Phase 3 trials, CMTP staff and the authors drafted recommendations for Pragmatic Phase 3 Pharmaceutical Trials. This draft was circulated first to technical working group members for their comments. After revising the document based on these comments, it was distributed electronically to other select experts and then made available for public comment. The final version of the EGD appears on the CMTP website. RESULTS: The process resulted in a set of 10 recommendations for conducting Phase 3 trials that met regulatory needs while addressing information important to physicians, patients, payers, and policy-makers. These recommendations encompassed three primary areas: generalizability from the trial participants to the clinical population of interest; effectiveness relative to active comparators; and consistently measured relevant outcomes for coverage and treatment decisions. LIMITATIONS: While stakeholders were involved throughout the process, not all recommendations will meet the needs of all stakeholders. CONCLUSIONS: Pragmatic trial design need not be deferred until a product is in widespread use. Incremental movement toward the more pragmatic design of Phase 3 trials is desirable.

Improving the efficiency and effectiveness of pragmatic clinical trials in older adults in the United States.

Pragmatic clinical trials (PCTs) seek to improve the generalizability and increase the statistical power of traditional explanatory trials. They are a major tenet of comparative effectiveness research. While a powerful study design, PCTs have been limited by high cost, modest efficiency, and limited ability to fill relevant evidence gaps. Based on an American Reinvestment and Recovery Act (ARRA) supported meeting of national stakeholders, we propose several innovations and future research that could improve the efficiency and effectiveness of such studies focused in the U.S. Innovations discussed include optimizing the use of community based practices through partnership with Practice Based Research Networks (PBRNs), using information technology to simplify PCT subject recruitment, consent and randomization processes, and utilizing linkages to large administrative databases, such as Medicare, as a mechanism to capture outcomes and other important PCT variables with lower subject and research team burden. Testing and adaptation of such innovations to PCT are anticipated to improve the public health value of these increasingly important studies.

Access with evidence development: the US experience.

The concept of access with evidence development (AED), also known as 'coverage with evidence development' in the Medicare programme, has long been discussed as a policy option for ensuring more appropriate use of new technologies in the US. This article provides a comprehensive overview of more than 10 years of US experience with AED, both in the public and private healthcare sectors. Beginning with a discussion of the successes of private plans' conditional coverage for high-density chemotherapy for autologous bone marrow transplants for metastatic breast cancer and Medicare's conditional coverage of lung-volume-reduction surgery in the 1990s, the article moves on to describe how Medicare worked to codify AED as one of its coverage policy options in the early part of this decade. More recent private and public sector initiatives are also discussed, including an overview of barriers to implementing AED. Despite the complexity of political, financial and ethical issues faced in implementation, AED is now a permanent fixture of US coverage policy. Future initiatives within the Medicare programme and with private payers in the US are much more likely to succeed by relying upon the simple but consequential principles laid out at a Summit convened in Banff, Alberta, Canada in 2009 and presented in another article in this issue.

Impact of Medicare Part D on access to and cost sharing for specialty biologic medications for beneficiaries with rheumatoid arthritis.

OBJECTIVE: Many worry that the use of specialty tiering for biologic disease-modifying antirheumatic drugs (DMARDs) by Medicare Part D plans imposes a heavy financial burden on beneficiaries with rheumatoid arthritis (RA). To date, no one has examined the cost-sharing structures for biologic DMARDs in Part D plans or the resulting cost burden for patients. METHODS: We followed 14,929 vulnerable, low-income patients with RA who were enrolled in the Medicare Replacement Drug Demonstration (MRDD) in 2005. As the MRDD population transitioned into Part D in 2006, we examined correlates of Part D enrollment and compared the cost-sharing provisions for biologic DMARDs in the Medicare Advantage and stand-alone plans. We simulated the out-of-pocket costs of beneficiaries under 3 cost-sharing scenarios. RESULTS: Eighty-one percent of MRDD beneficiaries with RA enrolled in Part D. Enrollment predictors were female sex (odds ratio [OR] 1.48, 95% confidence interval [95% CI] 1.32-1.67), prior MRDD benefit use (OR 2.29, 95% CI 2.04-2.58), other self-reported drug coverage (OR 1.53, 95% CI 1.36-1.71), and receiving an MRDD subsidy (OR 2.00, 95% CI 1.74-2.30). Compared with stand-alone plans, Medicare Advantage plans had lower deductibles, lower premiums, and fewer prior authorization, step therapy, and quantity limit restrictions. However, approximately 75% of all plans used coinsurance as the preferred form of cost sharing. Out-of-pocket costs exceeded $4,000 annually in all cost-sharing scenarios. CONCLUSION: Most MRDD beneficiaries with RA enrolled in Part D. Although plans assume some costs for biologic DMARDs, the majority of costs are shifted to beneficiaries and to Medicare. Such cost shifting may place these medications out of the beneficiary's financial reach and expose Medicare to high financial liability.

The implementation of Medicare's outpatient prospective payment system and specific concerns for rural hospitals.

The transition to Medicare's new prospective payment system for hospital outpatient services has arguable been the most complex and difficult programmatic change in the history of Medicare (Federal Register, 2002). Concern about its adverse effects led to holding rural hospitals with 100 beds or fewer harmless from the financial consequences of the new payment system for the first three years. However, small rural hospitals were not held harmless from implementing the outpatient prospective payment system (OPPS). Many outside observers felt that small rural hospitals would be ill-equipped to handle the immensity of change required, and that claim denials or delays caused by inaccurate claims submissions might have a disproportionate effect on smaller hospitals. There were also reports about difficulties with the interim payment system that had been designed to ensure small hospitals did not lose money during the first three years. This policy brief describes issues that arose in implementing OPPS during the first years of the program, identifies specific implementation concerns for small rural hospitals, and raises issues that may warrant further research or policy action.