The DiSC assay - A cost-effective guide to treatment for chronic lymphocytic leukemia?

The differential staining cytotoxicity (DISC) assay involves in vitro drug panel testing against patient tumor cells to identify optimal therapy. This observational study investigated whether DISC assay guided treatment could improve outcome in patients with chronic lymphocytic leukemia. A cohort of 178 patients were categorized either as sensitive to drugs in vitro and receiving a sensitive drug in vivo, sensitive in vitro but not treated with a sensitive drug, or having disease resistant to all drugs tested in vitro. Response and survival for these patient categories were compared using multivariate regression techniques. Patients receiving a sensitive drug, compared with those who though having sensitivity did not, had a higher remission rate (odds ratio, 6.5; 95% CI, 2.91-14.53) and reduced death rate (hazard ratio, 0.29; 95% CI, 0.16-0.53). Having adjusted for all known confounding factors, the results suggest that in vitro drug sensitivity is an important independent prognostic variable to include in future trials, and that the DiSC assay may be a cost-effective use of health resources: the estimated incremental cost-effectiveness was $1,470 per life-year gained. A randomized controlled trial is required to confirm the benefit and estimate reliably the potential impact of assay-guided choice of therapy

Economic Evaluation of Medical Devices

There are a number of challenges in the economic evaluation of medical devices (MDs). They are typically less regulated than pharmaceuticals, and the clinical evidence requirements for market authorization are generally lower. There are also specific characteristics of MDs, such as the device–user interaction (learning curve), the incremental nature of innovation, the dynamic nature of pricing, and the broader organizational impact. Therefore, a number of initiatives need to be taken in order to facilitate the economic evaluation of MDs. First, the regulatory processes for MDs need to be strengthened and more closely aligned to the needs of economic evaluation. Second, the methods of economic evaluation need to be enhanced by improving the analysis of the available clinical data, establishing high-quality clinical registries, and better recognizing MDs’ specific characteristics. Third, the market entry and diffusion of MDs need to be better managed by understanding the key influences on MD diffusion and linking diffusion with cost-effectiveness evidence through the use of performance-based risksharing arrangements

Modeling in Early Stages of Technology Development: Is an iterative approach needed? : Comment on “Problems and Promises of Health Technologies: The Role of Early Health Economic Modeling”

A recent paper by Grutters et al makes the case for early health economic modeling in the development of health technologies. A number of examples of the value of early modeling are given, with analyses being performed at different stages in the development of several non-drug health technologies. This commentary acknowledges the contribution of the paper by Grutters et al and argues for an iterative and integrated approach to early modeling, assessing the cost-effectiveness of the technology, the value of future research and the interaction with the manufacturer’s pricing and revenue expectations

Challenges with Coverage with Evidence Development Schemes for Medical Devices : A Systematic Review

Objectives: Coverage with evidence development (CED) schemes are particularly relevant for medical devices (MDs), since clinical evidence is often limited at the time of launch and their long-term (cost-) effectiveness heavily depends on how they are adopted into routine clinical practice. The objective of this study was to identify and describe the challenges that payers and manufacturers might face when assessing the desirability of, choosing the research design for, implementing, and evaluating CED schemes for MDs. Methods: A systematic literature review was performed on six databases following PRISMA guidelines. Two independent reviewers assessed the eligibility of studies based on predefined criteria and extracted data from the included articles by using a pre-defined extraction template. The data were synthesised in a narrative review. Results: The systematic search yielded 4,293 articles of which 27 were eligible for inclusion. We identified 20 challenges that are associated with CED schemes for MDs. Five of these challenges relate directly to the characteristics of MDs, and hence are specific to MDs. These challenges concern deciding on whether a CED scheme is required, understanding the relevant uncertainties and risks, identifying meaningful outcomes, defining an adequate duration for a scheme, and market entry of new technologies. Conclusions: Payers and manufacturers of MDs have to address the identified challenges to improve a CED scheme’s chance of success. This can be further improved by public sharing of information about the outcome of applied schemes and way in which stakeholders have addressed the challenges they faced when applying a CED scheme

High-Dose Inactivated Influenza Vaccine is Associated with Cost Savings and Better Outcomes Compared to Standard-Dose Inactivated Influenza Vaccine in Canadian Seniors

Seasonal influenza infects approximately 10-20% of Canadians each year, causing an estimated 12,200 hospitalizations and 3,500 deaths annually, mostly occurring in adults ≥65 years old (seniors). A 32,000-participant, randomized controlled clinical trial (FIM12; Clinicaltrials.gov NCT01427309) showed that high-dose inactivated influenza vaccine (IIV-HD) is superior to standard-dose vaccine (SD) in preventing laboratory-confirmed influenza illness in seniors. In this study, we performed a cost-utility analysis (CUA) of IIV-HD versus SD in FIM12 participants from a Canadian perspective. Healthcare resource utilization data collected in FIM12 included: medications, non-routine/urgent care and emergency room visits, and hospitalizations. Unit costs were applied using standard Canadian cost sources to estimate the mean direct medical and societal costs associated with each vaccine (2014 CAD). Clinical illness data from the trial were mapped to quality-of-life data from the literature to estimate differences in effectiveness between vaccines. Time horizon was one influenza season, however, quality-adjusted life-years (QALYs) lost due to death during the study were captured over a lifetime. A probabilistic sensitivity analysis (PSA) was also performed. Average per-participant medical costs were $47 lower and societal costs$60 lower in the IIV-HD arm. Hospitalizations contributed 91% of the total cost and were less frequent in the IIV-HD arm. IIV-HD provided a gain in QALYs and, due to cost savings, dominated SD in the CUA. The PSA indicated that IIV-HD is 89% likely to be cost saving. In Canada, IIV-HD is expected to be a less costly and more effective alternative to SD, driven by a reduction in hospitalizations

Time to review the role of surrogate endpoints in health policy: state of the art and the way forward

The efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. However, market access and coverage decisions are often based on surrogate endpoints, biomarkers, or intermediate endpoints, which aim to substitute and predict patient-relevant outcomes that are unavailable due to methodological, financial, or practical constraints. We provide a summary of the current use of surrogate endpoints in healthcare policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policy makers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and healthcare systems

Should Health Technology Assessment be more patient-centric? If so, how?

Health technology assessment (HTA) methods and processes have been criticized for not being sufficiently ‘patient centric’. For example, Perfetto [1] argued that a proposed approach for assessing the value of health care interventions had not sufficiently incorporated a patient perspective and suggested that it represented a ‘missed opportunity’. A similar point was made about the other ‘value assessment frameworks’ developed recently in the United States [2]. In addition, Slejko et al. [3] proposed some key elements of a ‘patient informed’ reference case for conducting economic evaluations, which would supplement reference cases outlined by groups such as the second Panel on Cost-Effectiveness in Health and Medicine [4], by including consideration of elements such as convenience in receiving care, effects on the patient’s family, examination of whether quality of life instruments include the most relevant domains and a model structure for the economic evaluation that adequately reflects the patient’s journey through the various treatment options. While the case to consider the patient perspective is strong, the way in which it should be incorporated in HTA is not obvious. Most HTA analysts would argue that HTAs, with the possible exception of some that are undertaken to support the development of clinical guidelines, or initiatives such as shared (clinical) decision-making, are conducted for those making decisions about the allocation of health care resources for a given population. This population may be the enrollees of a given health plan or, in the case of national health services or national insurance schemes, the whole population of a given country. The population would include patients who currently have the disease of interest, their families, those who have been patients in the past and those who may contract the disease in the future, as well as those past, present and future sufferers of other diseases. Of course, there may be considerable similarity between the perspective of patients currently suffering from a disease and the population at large, but this is not necessarily the case [5, 6, 7]. Therefore, making HTA more patient centric may not be as simple as it appears. The case for considering the patient perspective may differ by type of health care system [8]. For example, in a private insurance-based system, where a substantial proportion of the payments may be made directly by the patients, one might expect more consideration of the patient perspective than in a publicly funded national health service. The empirical evidence generated in the recent years shows that there is greater awareness about the importance of patients’ views in HTA, but there is no common understanding of what “patient-centric HTA” actually means [9]. Here, we attempt to shed further light on the issue by conceptualizing “patient centricity” in two ways: (a) encouraging patients’ engagement in HTA process and (b) enlarging the scope of evidence in HTA to include patients’ outcomes and preferences (HTA methods). We discuss the opportunities and challenges of each, by providing some recent examples from different countries. Finally, we discuss some additional ways to make HTA more patient centric

Approaches to Aggregation and Decision Making - A Health Economics Approach : An ISPOR Special Task Force Report [5]

The fifth section of our Special Task Force report identifies and discusses two aggregation issues: 1) aggregation of cost and benefit information across individuals to a population level for benefit plan decision making and 2) combining multiple elements of value into a single value metric for individuals. First, we argue that additional elements could be included in measures of value, but such elements have not generally been included in measures of quality-adjusted lifeyears. For example, we describe a recently developed extended costeffectiveness analysis (ECEA) that provides a good example of how to use a broader concept of utility. ECEA adds two features—measures of financial risk protection and income distributional consequences. We then discuss a further option for expanding this approach—augmented CEA, which can introduce many value measures. Neither of these approaches, however, provide a comprehensive measure of value. To resolve this issue, we review a technique called multicriteria decision analysis that can provide a comprehensive measure of value. We then discuss budget-setting and prioritization using multicriteria decision analysis, issues not yet fully resolved. Next, we discuss deliberative processes, which represent another important approach for population- or plan-level decisions used by many health technology assessment bodies. These use quantitative information on CEA and other elements, but the group decisions are reached by a deliberative voting process. Finally, we briefly discuss the use of stated preference methods for developing “hedonic” value frameworks, and conclude with some recommendations in this area