Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens.

BACKGROUND: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies. OBJECTIVES: This study describes challenges in assessing PO and TA medicines, explores possible solutions, and provides actionable recommendations to facilitate an iterative life-cycle assessment of these medicines. METHODS: After reviewing the published literature, we obtained insights from key stakeholders and European experts across a range of disciplines, through individual interviews and an industry workshop. The research was guided and refined by an international expert committee through 2 sounding board meetings. RESULTS: The current challenges faced by PO and TA medicines are multiple and can be demonstrated through real-world examples of the current barriers and opportunities. A life-cycle approach to assessment should be taken, including key actions at the early stages of evidence generation, regulatory and reimbursement stage, as well as payment and adoption solutions that make use of the evolving evidence base. Working toward these solutions to maximize PO medicine value is a shared responsibility and stands to benefit all stakeholders. CONCLUSIONS: Our call to action is to expand access to comprehensive genomic testing, foster a learning health care system, enable fast and equitable access to cost-effective treatments, and ultimately improve health outcomes.

People get ready! A new generation of Alzheimer's therapies may require new ways to deliver and pay for healthcare.

The development of disease-modifying therapies (DMTs) for Alzheimer's disease (AD) has progressed over the last decade, and the first-ever therapies with potential to slow the progression of disease are approved in the United States. AD DMTs could provide life-changing opportunities for people living with this disease, as well as for their caregivers. They could also ease some of the immense societal and economic burden of dementia. However, AD DMTs also come with major challenges due to the large unmet medical need, high prevalence of AD, new costs related to diagnosis, treatment and monitoring, and uncertainty in the therapies' actual clinical value. This perspective article discusses, from the broad perspective of various health systems and stakeholders, how we can overcome these challenges and improve society's readiness for AD DMTs. We propose that innovative payment models such as performance-based payments, in combination with learning healthcare systems, could be the way forward to enable timely patient access to treatments, improve accuracy of cost-effectiveness evaluations and overcome budgetary barriers. Other important considerations include the need for identification of key drivers of patient value, the relevance of different economic perspectives (i.e. healthcare vs. societal) and ethical questions in terms of treatment eligibility criteria.

Digital cognitive behavioural therapy for insomnia and primary care costs in England: an interrupted time series analysis.

BACKGROUND: Sleepio is an automated digital program that delivers digital cognitive behavioural therapy for insomnia (dCBT-I). Sleepio has been proven effective in improving sleep difficulties; however, evidence for the possible impact of Sleepio use on healthcare costs in the UK has not, to the authors' knowledge, previously been developed. AIM: To identify the effect of a population-wide rollout of Sleepio in terms of primary care costs in the NHS in England. DESIGN & SETTING: The study was conducted in the Thames Valley region of England, where access to Sleepio was made freely available to all residents between October 2018 and January 2020. The study relies on a quasi-experimental design, using an interrupted time series (ITS) to compare the trend in primary care costs before and after the rollout of Sleepio. METHOD: Primary care data for people with relevant characteristics from nine general practices in Buckinghamshire was used. Primary care costs include general practice contacts and prescriptions. Segmented regression analysis was used to estimate primary and secondary outcomes. RESULTS: For the 10 705 patients included in the sample, the total saving over the 65-week follow-up period was £71 027. This corresponds to £6.64 per person in the sample or around £70.44 per Sleepio user. Secondary analyses suggest that savings may be driven primarily by reductions in prescribing. CONCLUSION: Sleepio rollout reduced primary care costs. National adoption of Sleepio may reduce primary care costs by £20 million in the first year. The expected impact on primary care costs in any particular setting will depend on the uptake of Sleepio.

Outcome-Based Payment Schemes: What Outcomes Do Patients with Cancer Value?

BACKGROUND: Uncertainty about the benefits new cancer medicines will deliver in clinical practice risks delaying patient access to new treatment options in countries such as England, where the cost effectiveness of new medicines affects reimbursement decisions. Outcome-based payment (OBP) schemes, whereby the price paid for the drug is linked to patients' real-world treatment outcome(s) has been put forward as a mechanism to accelerate access. Although OBP schemes have generally focused on clinical outcomes to determine reimbursement, the degree to which these represent the outcomes that are important to patients is unclear. OBJECTIVE: To advance the application of OBP we ask, what outcomes do patients with cancer value (most) that might form a practical basis for OBP? METHODS: A review of the literature on outcomes in cancer produced a long list of candidates. These were evaluated in a focus group with patients with cancer and were then, in a second focus group, distilled to a shortlist of ten outcomes using a card sort method. The ten outcomes were included in an online survey of patients with cancer and carers, who were asked to rank the importance of each outcome. RESULTS: The focus groups identified a range of both clinical and functional outcomes that are important to patients. Analyses of the 164 survey responses suggested that the four most important outcomes to patients and carers are survival; progression, relapse or recurrence; post-treatment side effects; and return to normal activities of daily life. CONCLUSION: Commissioners of cancer services wishing to instigate an OBP scheme should prioritise collecting data on these outcomes as they are important to patients. Of these, only mortality data are routinely collected within the national health service (NHS). Progression and some morbidity data exist but are not currently linked, creating a challenge for OBP.

Training in Neurology: Adoption of resident teleneurology training in the wake of COVID-19: Telemedicine crash course.

The coronavirus disease 2019 pandemic has changed the way we engage patient care, with a move toward telemedicine-based health care encounters. Teleneurology is now being rapidly embraced by neurologists in clinics and hospitals nationwide but for many, this paradigm of care is unfamiliar. Exposure to telemedicine in neurology training programs is scarce despite previous calls to expand teleneurology education. Programs that provide a teleneurology curriculum have demonstrated increased proficiency, accuracy, and post-training utilization among their trainees. With the current changes in health care, broad incorporation of teleneurology education in resident and fellow training after this pandemic dissipates will only serve to improve trainee preparedness for independent practice.

Policy perspectives on alternative models for pharmaceutical rebates: a report from the Institute for Clinical and Economic Review Policy Summit.

Alternative approaches to the current rebate system are being considered by policymakers and stakeholders in the private insurance market. This paper presents an analysis of three alternative options to the current rebate model: retaining retroactive rebates but requiring 100% pass-through of rebates and fees to plan sponsors; retaining retroactive rebates but requiring that patients share in rebates at the point of sale; and eliminating retroactive rebates and replacing the current structure with upfront discounts. Each alternative approach presents a balance of potential advantages and disadvantages. Policymakers should not assume that switching to an alternative rebate model will deliver unalloyed benefits for patients and the health system.

Benchmarking Telestroke Proficiency: Page-to-Needle Time Among Neurovascular Fellows and Attendings.

BACKGROUND AND PURPOSE: Formal telestroke training for neurovascular fellows (NVFs) is necessary because of growing use of telestroke technologies in the management of acute ischemic stroke; yet, educational approaches and training benchmarks are not formalized. Time between telestroke consultant page and tissue-type plasminogen activator administration (page-to-needle time, PTNT) can provide an objective measure of proficiency. We compared PTNT between NVFs and neurovascular attendings (NVAs) and evaluated changes in PTNT with experience. METHODS: We identified suspected acute ischemic stroke patients in our telestroke registry from July 2013 to December 2015 who received tissue-type plasminogen activator. Using multivariable quantile regression, we estimated the difference and 95% confidence interval in median PTNT between NVFs and NVAs. We also report the coefficient of change in PTNT over increasing number of telestroke consults. RESULTS: NVFs evaluated 53.7% of 618 tissue-type plasminogen activator cases over telestroke. NVAs had significantly shorter PTNT compared with NVFs, with a difference in median PTNT of -9 minutes (95% confidence interval, -12.3 to -5.7). This difference persisted when adjusted for relative tissue-type plasminogen activator contraindications. For each additional telestroke consult, PTNT decreased by 0.07 minutes for NVFs or NVAs (P=0.02 and <0.01, respectively). CONCLUSIONS: PTNT improves by ≈1 minute for every 14 consults for both NVFs and NVAs. Our findings support the importance of integrating telestroke training into supervised neurovascular fellowships to increase proficiency prior to independent practice and suggest that PTNT can be a benchmark for tracking proficiency.

A Review of NICE Methods and Processes Across Health Technology Assessment Programmes: Why the Differences and What is the Impact?

BACKGROUND: Decisions made by the National Institute for Health and Care Excellence (NICE) exert an influence on the allocation of resources within 'fixed' National Health Service budgets. Yet guidance for different types of health interventions is handled via different 'programmes' within NICE, which follow different methods and processes. OBJECTIVE: The objective of this research was to identify differences in the processes and methods of NICE health technology assessment programmes and to explore how these could impact on allocative efficiency within the National Health Service. METHODS: Data were extracted from the NICE technology appraisal programme, medical technologies guidance, diagnostic assessment programme, highly specialised technologies programme, and clinical guidelines process and methods manuals to undertake a systematic comparison. Five qualitative interviews were carried out with NICE members of staff and committee members to explore the reasons for the differences found. RESULTS: The main differences identified were in the required evidence review period, or lack thereof, mandatory funding status, the provision of a reference case for economic evaluation, the requirement for and the type of economic analysis undertaken, and the decision making criteria used for appraisal. CONCLUSION: Many of the differences found can be justified on grounds of practicality and relevance to the health technologies under assessment. Nevertheless, from a strict utilitarian view, there are several potential areas of inefficiency that could lead to the misallocation of resources within the National Health Service, although some of these might be eliminated or reduced if an egalitarian view is taken. The challenge is determining where society is willing to trade health gains between different people.

Sources and Characteristics of Utility Weights for Economic Evaluation of Pediatric Vaccines: A Systematic Review.

BACKGROUND: Cost-effectiveness analysis of pediatric vaccines for infectious diseases often requires quality-of-life (utility) weights. OBJECTIVE: To investigate how utility weights have been elicited and used in this context. METHODS: A systematic review was conducted of studies published between January 1990 and July 2013 that elicited or used utility weights in cost-effectiveness analyses of vaccines for pediatric populations. The review focused on vaccines for 17 infectious diseases and is presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. RESULTS: A total of 6410 titles and abstracts and 225 full-text articles were reviewed. Of those selected for inclusion (n = 101), 15 articles described the elicitation of utility weights and 86 described economic modeling studies using utilities. Various methods were used to generate utilities, including time trade-off, contingent valuation, and willingness to pay, as well as a preference-based measure with associated value sets, such as the EuroQol five-dimensional questionnaire or the Health Utilities Index. In modeling studies, the source of utilities used was often unclear, poorly reported, or based on weak underlying evidence. We found no articles that reported on the elicitation or use of utilities in diphtheria, polio, or tetanus. CONCLUSIONS: The scarcity of appropriate utility weights for vaccine-preventable infectious diseases in children and a lack of standardization in their use in economic assessments limit the ability to accurately assess the benefits associated with interventions to prevent infectious diseases. This is an issue that should be of concern to those making decisions regarding the prevention and treatment of infectious childhood illnesses.

HEADROOM APPROACH TO DEVICE DEVELOPMENT: CURRENT AND FUTURE DIRECTIONS.

OBJECTIVES: The headroom approach to medical device development relies on the estimation of a value-based price ceiling at different stages of the development cycle. Such price-ceilings delineate the commercial opportunities for new products in many healthcare systems. We apply a simple model to obtain critical business information as the product proceeds along a development pathway, and indicate some future directions for the development of the approach. METHODS: Health economic modelling in the supply-side development cycle for new products. RESULTS: The headroom can be used: initially as a 'reality check' on the viability of the device in the healthcare market; to support product development decisions using a real options approach; and to contribute to a pricing policy which respects uncertainties in the reimbursement outlook. CONCLUSIONS: The headroom provides a unifying thread for business decisions along the development cycle for a new product. Over the course of the cycle attitudes to uncertainty will evolve, based on the timing and manner in which new information accrues. Within this framework the developmental value of new information can justify the costs of clinical trials and other evidence-gathering activities. Headroom can function as a simple shared tool to parties in commercial negotiations around individual products or groups of products. The development of similar approaches in other contexts holds promise for more rational planning of service provision.