Protecting Medicare's Discretion to Say No to Unproven Therapies.

In this Viewpoint, Kesselheim and coauthors discuss 2 bills in Congress that would curtail Medicare's ability to decline, limit, or conditionally cover medical products that lack robust evidence and argue that officials should distinguish between better and worse therapies when determining reimbursement.

Key Considerations in the Health Technology Assessment of Advanced Therapy Medicinal Products in Scotland, The Netherlands, and England.

OBJECTIVES: Advanced therapy medicinal products (ATMPs) are highly innovative therapies. Their costs and uncertain value claims have raised concerns among health technology assessment (HTA) bodies and payers. Little is known about how underlying considerations in HTA of ATMPs shape assessment and reimbursement recommendations. We aim to identify and assess key considerations that played a role in HTA of ATMPs underlying reimbursement recommendations. METHODS: A review of HTA reports was conducted of all authorized ATMPs in Scotland, The Netherlands, and England. Considerations were extracted and categorized into EUnetHTA Core Model domains. Per jurisdiction, considerations were aggregated and key considerations identified (defined as occurring in >1/assessment per jurisdiction). A narrative analysis was conducted comparing key considerations between jurisdictions and different reimbursement recommendations. RESULTS: We identified 15 ATMPs and 18 HTA reports. In The Netherlands and England most key considerations were identified in clinical effectiveness (EFF) and cost- and economic effectiveness (ECO) domains. In Scotland, the social aspects domain yielded most key considerations, followed by ECO and EFF. More uncertainty in evidence and assessment outcomes was accepted when orphan or end-of-life criteria were applied. A higher percentage of considerations supporting recommendations were identified for products with positive recommendations compared with restricted and negative recommendations. CONCLUSIONS: This is the first empirical review of HTA's using the EUnetHTA Core Model to identify and structure key considerations retrospectively. It provides insights in supporting and opposing considerations for reimbursement of individual products and differences between jurisdictions. Besides the EFF and ECO domain, the social, ethical, and legal domains seem to bear considerable weight in assessment of ATMPs.

Cost-effectiveness analysis of using innovative therapies for the management of moderate-to-severe ulcerative colitis in Spain.

BACKGROUND: To evaluate the cost-effectiveness of tofacitinib in comparison to vedolizumab for the treatment of moderate-to-severe ulcerative colitis (UC) after failure or intolerance to conventional therapy (bio-naive) or first-line biologic treatment (bio-experienced), from the Spanish National Health System (NHS) perspective. METHODS: A lifetime Markov model with eight-week cycles was developed including five health states: remission, response, active UC, remission after surgery, and death. Response and remission probabilities (for induction and maintenance periods) were obtained from a multinomial network meta-analysis. Drug acquisition - biosimilar prices included - (ex-factory price with mandatory deductions), administration, surgery, patient management, and adverse event management costs (€, year 2019) were considered. A 3% discount rate (cost/outcomes) was applied. Probabilistic and deterministic sensitivity analyses (PSA) were conducted. RESULTS: Tofacitinib was dominant versus vedolizumab (both in bio-naive and bio-experienced patients) entailing total cost savings of €23,816 (bio-naïve) and €11,438 (bio-experienced). Differences in quality-adjusted life-year (QALY) were smaller than 0.1 for both populations. PSA results showed that tofacitinib has a high probability of being cost-effective (bio-naïve: 82.5%; bio-experienced: 90.6%) versus vedolizumab. CONCLUSIONS: From the Spanish NHS perspective, tofacitinib could be a dominant treatment (less costly and more effective) in comparison to vedolizumab, with relevant cost savings and similar QALY gains.

Current Attitudes toward Unfunded Cancer Therapies among Canadian Medical Oncologists.

BACKGROUND: Despite successes in the development of innovative anticancer therapies, the fiscal and capacity restraints of the Canadian public healthcare system result in challenges with drug access. A meaningful proportion of systemic therapies ultimately do not receive public funding despite supporting clinical evidence. In this study, we assessed Canadian medical oncologists' current attitudes toward discussing publicly unfunded cancer treatments with patients and predictors of different practices. METHODS: A web-based survey consisting of multiple choice and case-based scenarios was distributed to medical oncologists identified through the Royal College of Physicians and Surgeons of Canada directory. RESULTS: A total of 116 responses were received. Almost all respondents reported discussing publicly unfunded treatments, including those who did so for Health Canada (HC) approved treatments (50%) and those who discussed off-label treatments (i.e., not HC approved) as guided by national guidelines (48%). Respondents in practice for over 15 years versus less than 5 years (OR 0.14, 95% CI 0.04-0.50, p = 0.002) and those who worked in a community practice versus comprehensive cancer center (OR 0.17, 95% CI 0.03-0.91, p = 0.04) were significantly less likely to discuss off-label treatment options with their patients. Almost half of respondents (47%) indicated that their institution did not permit the administration of unfunded treatments. CONCLUSIONS: There is variability in medical oncologists' practices when it comes to discussing unfunded therapies. Given the limitations within Canada's publicly funded healthcare system, physicians are faced with the challenge of navigating an increasingly complex balance between patient care and available resources. Engagement of relevant stakeholders and policy makers is crucial in the continued evaluation of Canada's drug funding process.

Information Opacity in Biopharmaceutical Innovation Through the Lens of COVID-19.

The COVID-19 pandemic has revealed myriad and complex challenges for our national health care system spanning preparedness, response, access, costs, infrastructure, coordination, and medical innovation. These challenges implicate federal, state, and local agencies and actors, as well as international collaborative bodies. One constant throughout the pandemic has been the pressing need for safe and effective diagnostics, prophylactic vaccines, and drug treatments to counter the virus.1 Inarguably, significant problems with the multi-faceted system of drug and vaccine innovation and regulation manifested long before the COVID-19 pandemic.2 The pandemic, however, has laid bare the inextricable connections among federal funding, patents, product review and approval mechanisms, and the eventual medical products and resulting costs.

Adaptive innovations to provide services to children with developmental disabilities during the COVID-19 pandemic.

Children with developmental disabilities are experiencing significant challenges to service access due to suspension of in-person assessments during the current COVID-19 pandemic. Telehealth is rapidly becoming the new service delivery model, which presents a unique opportunity for innovation in care that could be beneficial in the post-pandemic period. For example, using a combination of in-home video and telehealth options could form the first step in developmental assessment, allowing children to receive the necessary supports without delay. Recent telehealth funding is welcome but additional Medicare items for joint consultations including general practitioners (GPs), and paediatric, mental health and allied health professionals is critical.

Establishment and implementation of Cancer Genomic Medicine in Japan.

Approximately 1 in 2 Japanese people are estimated to be diagnosed with cancer during their lifetime. Cancer still remains the leading cause of death in Japan, therefore the government of Japan has decided to develop a better cancer control policy and launched the Cancer Genomic Medicine (CGM) program. The Ministry of Health, Labour, and Welfare (MHLW) held a consortium at their headquarters with leading academic authorities and the representatives of related organizations to discuss ways to advance CGM in Japan. Based on the report of the consortium, the CGM system under the national health insurance system has gradually been realized. Eleven hospitals were designated in February 2018 as core hospitals for CGM; subsequently, the MHLW built the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) as an institution to aggregate and manage genomic and clinical information on cancer patients, and support appropriate secondary use of the aggregated information to develop research aimed at medical innovation. As the first step in Japan's CGM in routine practice, in June 2019 the MHLW started reimbursement of 2 types of tumor profiling tests for advanced solid cancer patients using the national insurance system. Japan's CGM has swiftly been spreading nationwide with the collaboration of 167 hospitals and patients. The health and research authorities are expected to embody personalized cancer medicine and promote CGM utilizing state-of-the-art technologies.

Work-Sampling Study of an Innovative Care Coordination Program Aimed at Children With Chronic Health Conditions.

PURPOSE OF STUDY: To estimate time allocation and labor cost for care coordinators (CCs), community health workers (CHWs), and mental health workers (MHWs) to conduct care coordination tasks in a pediatric care coordination program. PRIMARY PRACTICE SETTING: A public tertiary academic medical center in Chicago, IL. METHODOLOGY AND SAMPLE: A work-sampling study was conducted using a text message-based survey on 5 CCs, 20 CHWs, and 4 MHWs who volunteered to participate. Workers were randomly sampled within working hours to collect information on who was the subject of interaction and what service was being delivered over a 6-month period. Time allocation of workers to different subjects and services was summarized using descriptive statistics. RESULTS: Care coordinators allocated 41% of their time to managing CHW teams. Community health workers allocated 37% of time providing services directly to children and 26% to the parent/caregiver. Mental health workers allocated 16% of time providing services to children and 29% to the parent/caregiver. The care coordination program serviced 5,965 patients, with a total annual labor cost of $1,455,353. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Community health workers spent the majority of time working with patients and their families to conduct assessments. Mental health workers primarily addressed children's needs through their caregivers. Care coordinators primarily supported CHWs in coordinating care. Results may be used to inform development of such programs by determining services most often utilized, and labor cost may be used to inform program implementation and reimbursement.

Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial.

CONTEXT: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied. OBJECTIVE: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly. DESIGN AND SETTING: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center. PATIENTS: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment. INTERVENTION: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day). MAIN OUTCOME MEASURE: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy. RESULTS: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ±â€…1375 per month), arm C was most expensive (mean, $22543 ±â€…11158 per month), and arm A had an intermediate cost (mean, $14261 ±â€…1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%. CONCLUSIONS: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.

[What is the fair price of innovative therapy?] / L'innovation thérapeutique, à quel prix ?

TITLE: L'innovation thérapeutique, à quel prix ? ABSTRACT: Comment préserver l'accessibilité aux nouveaux médicaments pour tous les patients qui en ont besoin ? La question se pose à la lumière des prix exorbitants auxquels les thérapies géniques, mais aussi les biothérapies et de nouvelles molécules chimiques, sont commercialisées. L'analyse montre qu'à court/moyen terme, l'arrivée sur le marché d'un nombre croissant de nouveaux traitements à haute valeur ajoutée mais à des prix très élevés deviendra insoutenable pour les organismes payeurs qui sous-tendent notre système de santé. Les arguments de rentabilité invoqués par les sociétés pharmaceutiques pour justifier les prix proposés sont à tout le moins contestables, d'autant plus qu'ils ne sont pas documentés de façon transparente et que cette industrie jouit déjà de marges bénéficiaires considérables, en comparaison de celles d'autres secteurs du monde économique. Quant aux promesses de guérison définitive assurée par certains traitements, il faudra encore attendre quelques années pour en vérifier le fondement. À l'aube d'une réforme qui apparaît incontournable, nous formulons plusieurs propositions pour faire avancer le débat, en particulier : (1) mettre en œuvre la résolution avancée par plusieurs états membres de l'Organisation mondiale de la santé (OMS) pour assurer la transparence des coûts de développement des nouveaux médicaments ; (2) imposer une clause de prix raisonnable dans les accords qui régissent le transfert de technologies entre les institutions académiques soutenues par des fonds publics et les entreprises privées ; (3) instituer une instance européenne commune de négociation des prix des médicaments adaptée aux conditions socioéconomiques de chaque pays ; (4) conditionner le remboursement des traitements innovants à leur commercialisation par des entreprises - ou des filiales de celles-ci - répondant à des normes certifiant leur responsabilité sociétale et (5) développer en Europe des partenariats public-privé à but non lucratif, pour la création de quelques unités de production de biothérapies et thérapies géniques. L'objectif général de ces mesures serait de fixer un cadre qui permette de définir des prix qui garantissent un juste retour de l'investissement public vers le système de santé tout en assurant pour les entreprises un profit d'un niveau conforme au marché et une incitation suffisante à investir dans les domaines prioritaires pour la santé publique.

[Gene-based therapies of spinal muscular atrophy: a piece of history of medicine]. / Thérapies géniques de l'amyotrophie spinale infantile - Un morceau d'histoire de la médecine.

It is worth stating that a generation is needed to bring about a new family of drugs. After the deciphering of the genetic cause in 1995, two innovative classes of therapeutics are now available for spinal muscular atrophy (SMA): the repeated administration of antisens oligonucleotides and the one-shot administration of a scAAV9-SMN as a gene therapy. By addressing the genetic mechanisms of the disease, these drugs fundamentally change its course. These major advances in an extremely severe disease, often fatal before the age of 18 months in the type 1 form (50% of patients), pave the way for the treatment of other serious pathologies of the nervous or neuromuscular system, and provide unambiguous evidence of the effectiveness of these new classes of drugs called to address a number of genetic or acquired diseases. These breakthroughs raise also new scientific and technological questions (limited production yields of gene therapy drugs) but also ethical issues (access of patients to these innovative therapies) that resonate beyond this disease alone.

TITLE: Thérapies géniques de l'amyotrophie spinale infantile - Un morceau d'histoire de la médecine. ABSTRACT: On convient de dire qu'une génération est nécessaire pour faire émerger une nouvelle famille de médicaments. L'amyotrophie spinale infantile (SMA), après l'élucidation du gène causal en 1995, dispose depuis peu de deux classes innovantes de thérapeutiques : l'administration répétée d'oligonucléotides antisens et l'administration unique d'une thérapie génique par scAAV9-SMN. En s'adressant aux mécanismes génétiques de la maladie, elles en modifient fondamentalement le cours. Ces avancées majeures dans une maladie extrêmement sévère, mortelle souvent avant l'âge de 18 mois dans les formes de type 1 (50 % des malades), ouvrent la voie pour d'autres pathologies graves du système nerveux ou neuromusculaire, et apportent une preuve déterminante de l'efficacité de ces classes nouvelles de produits appelés à s'adresser à de nombreuses maladies génétiques ou acquises. Elles génèrent aussi de nouvelles questions d'ordre scientifique et technologique (capacités limitées de production des quantités nécessaires en thérapie génique) mais également d'ordre éthique (conditions d'accès des malades à ces thérapies innovantes), qui résonnent au-delà de cette seule maladie.

Use of Decision Analysis and Economic Evaluation in Upper Extremity Surgery: A Systematic Review.

BACKGROUND: Decision analysis allows clinicians to apply evidence-based medicine to guide objective decisions in uncertain scenarios. There is no comprehensive review summarizing the various decision analysis tools used. The authors aimed to appraise and review the decision analytic models used in hand surgery. METHODS: A search of English articles on the PubMed, Ovid, and Embase databases was performed. All articles, regardless of date of publishing, were considered. Two reviewers, based on strict inclusion criteria, independently assessed each article. RESULTS: The search resulted in 5525 abstracts, which yielded 30 studies that met inclusion criteria. Included studies were grouped according to medical indications, with scaphoid fractures (n = 6) and carpal tunnel syndrome (n = 5) being the most commonly reported. Included articles used decision analysis (n = 15) and/or economic analyses (n = 23) to discuss diagnostic strategies or compare treatments. The three most common outcomes reported were utility (n = 12), cost per quality-adjusted life-year (n = 16), and quality-adjusted life-years (n = 16). The decision analysis models compared diagnostic strategies, management options, and novel treatments. CONCLUSIONS: Decision analysis is increasingly popular in hand surgery. It is useful for comparing surgical strategies through evaluation of quality-of-life outcomes and costing data. The most common model was a simple decision tree. The quality of decision analysis models can be improved with the addition of sensitivity analysis. Surgeons should be familiar with the principles of decision analysis, so that complex decisions can be evaluated using rigorous probabilistic models that combine risks and benefits of multiple strategies.

Uncertainty and Cures: Discontinuation, Irreversibility, and Outcomes-Based Payments: What Is Different About a One-Off Treatment?

Payers are concerned that one-off "cures" bring great uncertainty with the consequential risk of incorrect adoption decisions, and significant budget impact from large one-off payments. Innovators worry about bias against "cures" in favor of repeat treatment, which is not in patients' interests. We find that even in the absence of a difference in uncertainty of outcomes, adverse pay-offs differ. The greater financial risk associated with a cure is related to the issue of treatment discontinuation, driven by irreversibility. This paper uses a stylized example to illustrate the need to separate three different elements of the issue: (i) one-off versus repeat or ongoing treatment, (ii) duration of treatment effect, and (iii) the potential role of financial arrangements or risk sharing to mitigate the financial risk to the payer. It concludes that: (i) prevalence and discontinuation issues mean that the impact on the payer of an incorrect decision is greater with a one-off treatment than a repeat therapy; (ii) with evidence collection this risk diminishes over time (a form of CED or OWR); and (iii) financial arrangements or risk sharing can eliminate differences for the payer as between one-off and repeat therapy. The impact of (iii) also addresses payer concerns about budget impact.

What Is the Value of Innovative Pharmaceutical Therapies in Oncology and Hematology? A Willingness-to-Pay Study in Bulgaria.

OBJECTIVES: To analyze the views of Bulgarian oncologists and hematologists regarding the value of innovative pharmaceutical treatments in their clinical area. METHODS: Physicians were invited to review a life-prolonging scenario and to indicate what minimum improvement in median survival a new treatment would have to generate for them to recommend it over the standard of care. Respondents were also asked to state the highest cost at which they would recommend a new therapy that would improve patient's health-related quality of life (HRQoL) but would have no impact on survival. In addition, physicians were asked whether they would consider different responses under certain circumstances. Responses were used to calculate incremental cost-effectiveness ratios (ICERs) for each scenario. RESULTS: In the life-prolonging scenario, participants required a median of 12-month improvement in the survival to reimburse a new therapy at an incremental cost of €50 000, implying a willingness-to-pay of €50 000 per QALY gained. In the HRQoL-enhancing scenario, respondents indicated a €100 000 median cost per QALY gained. We observed a significant variation in responses. Although the median ICER for better HRQoL was twice as high as the median ICER for longer survival, 5% trimmed mean values were almost equal. Physicians did not believe that a higher ICER should be used for the treatment of children or for rare diseases. CONCLUSIONS: We found a high willingness-to-pay for innovative drugs in oncology and hematology. The wide range of responses observed, however, indirectly implies a lack of consensus on the use of explicit ICER thresholds in Bulgaria.