Unlocking the full potential of rare disease drug development: exploring the not-for-profit sector's contributions to drug development and access.

This commentary provides a comprehensive overview of the challenges and opportunities in the field of drug development for rare diseases and especially of gene therapy products for ultra-rare diseases. It discusses the limited market size, reimbursement and scientific complexities that deter pharmaceutical investment in this field. Highlighting the pivotal role of charitable organizations like Fondazione Telethon, it showcases their efforts in funding research and ensuring access to innovative therapies. This commentary also addresses the challenges in therapy distribution, particularly regarding sustainability and global access. It outlines Fondazione Telethon's operational model to try to address these challenges. Finally, it appeals to governments and regulatory bodies to implement policies and incentives aimed at further fostering innovation and accessibility in rare disease drug development and access.

Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Thrombopoietin Receptor Agonists and Other Second-Line Therapies for Immune Thrombocytopenia: A Narrative Review With a Focus on Drug Access in Canada.

INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. After corticosteroids with or without intravenous immune globulin (first-line treatment), second-line treatment options include rituximab, splenectomy, thrombopoietin receptor agonists (TPO-RAs), and fostamatinib. In Canada, the choice of second-line therapy is influenced by access to medications. The goals of this narrative review are to 1) summarize the evidence for the use of TPO-RAs and other second-line therapies in ITP and 2) highlight differences in public funding criteria for TPO-RAs across provinces and territories in Canada. METHODS: We conducted a literature review of second-line therapies for ITP. We solicited information on public funding programs for TPO-RAs in Canada from health care providers, pharmacists, and provincial ministries of health. RESULTS: Head-to-head trials involving TPO-RAs, rituximab, splenectomy, and fostamatinib are lacking. There is substantial evidence of effect for TPO-RAs in improving platelet count levels, health-related quality of life, bleeding, and fatigue from placebo-controlled trials and observational studies; however, access to TPO-RAs through provincial funding programs in Canada is variable. Splenectomy failure is a prerequisite for the funding of TPO-RAs in Ontario, Manitoba, and Saskatchewan, but not in Alberta or Quebec. Other provinces either do not have access to public funding or funding is provided on a case-by-case basis. DISCUSSION: TPO-RAs are effective second-line therapies for the treatment of ITP; however, access is variable across Canada, which results in health disparities and poor uptake of international treatment guidelines.

Delayed and unmet prescription drug access linked to elevated anxiety symptoms during COVID-19: Retrospective findings from the NLSY79 child and young adult cohort.

Background: The COVID-19 pandemic produced substantial challenges to pharmacy systems worldwide and provoked concerns about a wider influence on mental health. While various studies have investigated the relationship between disruptions in access to healthcare and mental health, the effects of delayed and unmet access to prescription drugs on anxiety-related outcomes have been underexamined. Objective: This study analyzed the impact of delayed and unmet access to prescription drugs on anxiety-related outcomes, including anxiety, inability to stop or control worrying, worrying too much, trouble relaxing, trouble sitting still, being annoyed or irritable, and fear of future events, before and during the COVID-19 pandemic. Methods: A retrospective observational study was performed using the National Longitudinal Survey of Youth 79 Child and Young Adult dataset, encompassing 2193 individuals. One-way multivariate analysis of covariance (MANCOVA) analyses were conducted to examine the relationship between access to prescription drugs and anxiety-related symptoms. Results: The findings show that, before the pandemic, instances of delayed/unable to access prescription drugs were either not linked to anxiety symptoms or, in some cases, were linked to anxiety symptoms but no different than during the pandemic. Delayed access to prescription drugs amid the pandemic was significantly linked with increases in anxiety symptoms not found pre-pandemic, including worrying too much (F = 18.433, p < .001, η2p = 0.017), trouble relaxing (F = 11.423, p < .001, η2p = 0.010), and being easily annoyed or irritable (F = 3.881, p = .021, η2p = 0.004). Similarly, unmet access to prescription drugs amid the pandemic was significantly linked with increases in anxiety-related symptoms not found pre-pandemic, including an inability to stop or control worrying (F = 14.666, p < .001, η2p = 0.013) and worrying too much (F = 18.433, p < .001, η2p = 0.017). Conclusions: These results have implications for pharmacy administrators and policymakers seeking to understand and limit adverse mental health outcomes within pharmacy during times of crisis.

Insights from Japan’s cost-effectiveness analysis policy on pricing for China’s NRDL access / 中国药房

The cost-effectiveness analysis policy for drugs was institutionalized in Japan since 2019， realizing quantitative adjustment of price across varieties. A hierarchical categorization approach was adopted to select medicines with high expected annual sales. For selected medicines， adjustments were made to the premium and profit components within the existing price structure based on a pre-defined incremental cost-effectiveness ratio （ICER） threshold， effectively resolving the issue of inconsistent criteria and magnitudes caused by subjective judgment. Meanwhile， incentive measures like evaluation exemption or threshold enhancement were granted for specific medicines. Besides， a price adjustment mechanism， which was allowed for upward and downward adjustments， involving tiered ICER threshold and quantified formulas， had been established for the premium and profit components of drug price. In China’s National Reimbursement Drug List （NRDL） access， certain issues remained to be addressed： insufficient clarity in the quantitative mechanism of price formation， incomplete price adjustment measures， and lagging in the communication channels. It is recommended that the following measures could be referred to when further improving the scientificity and fairness of drug pricing during China’s NRDL access， such as enhancing the ICER threshold for medicines catering to special populations， quantifying criteria and extents for price adjustment， granting preferential pricing policies to pharmaceutical companies that present high-quality evidence of effectiveness， preceding communication channels with pharmaceutical companies， as well as exploring a price floor mechanism for the drugs with excessive price reduction.

The reimbursement decision speed for oncology new drugs in China and its determinant factors.

Introduction: China has initiated national price negotiations to improve access to innovative drugs. Learning the factors that contributed to the time gap from marketing authorization to reimbursement leads to more clarity to decision-making, which remains under-researched in China. Methods: We collected new oncology drug approvals that were marketed before 30 Jun 2022, using the Listed Drug Database of the Chinese drug agency. Major information of each approval was obtained from the published review report, including the first approval region (China or the US) and the receipt of expedited review pathways (priority review and conditional approval). The reimbursement lists issued by China National Healthcare Security Administration from 2015 to 2023 were used to determine the reimbursement status of drugs. The duration from marketing authorization to reimbursement was defined as the reimbursement decision speed, and the Cox regression was performed to explore the underlying factors. Results: A total of 186 oncology approvals were included. More than half of the approvals qualified for reimbursement (110[59.14%]), and the median reimbursement decision speed was accelerated from 540.5 days in the third-round negotiation to 448 days in the seventh-round. Domestic new drugs had a higher probability of being adopted by the Chinese payer than drugs developed by foreign companies (adjusted HR = 3.73, 95% CI 2.42 to 5.75; P < 0.001). Furthermore, new drug applications receiving the regular review pathway were more likely to be reimbursed (adjusted HR = 2.15, 95% CI 1.13 to 4.08; P = 0.020) compared to those approved under the conditional approval pathway. Discussion: These findings indicate that the Chinese government is actively working toward improving access to new oncology drugs. The faster reimbursement decision speed for domestic drugs might be attributed to their pricing advantages and the regulator's efforts to stimulate innovation in the domestic pharmaceutical industry. However, concerns about the uncertainty in drug benefits can affect the reimbursement decision-making, which suggests the delicate tradeoff between drug accessibility and risk involved in the reimbursement process.

Challenges and Strategies for Improving Access to Cancer Drugs in Malaysia: Summary of Opinions Expressed at the 2nd MACR International Scientific Conference 2022.

Considerable progress has been made in cancer drug development in recent decades. However, for people in low- and middle-income countries, including Malaysia, many of these drugs are not readily available. During the 2nd Malaysian Association for Cancer Research (MACR) International Scientific Conference, a forum discussion was held to address these challenges and explore strategies to improve access to cancer medicines in the country. This paper presents the results of the said forum discussion. A few challenges to cancer drug access were highlighted, including lengthy approval and regulatory practices, cost of medicines, and manufacturing barriers. Besides, a few strategies for mitigating some of these challenges were proposed, such as mechanisms for cost reduction, uptake of biosimilars and generics, local manufacturing, public-private partnerships, strengthening the role of insurance companies, funding and regulation, and advocacy for fair pricing, by drawing examples from cancer medicines access initiatives in Malaysia and initiatives for different disease groups. Overall, this paper provides a comprehensive overview of the challenges and strategies for improving access to cancer medicines in Malaysia and provides valuable insights for policymakers, healthcare providers, the pharmaceutical industry, cancer patients, cancer support groups, and other stakeholders working on this important issue.

Access to novel cancer medicines in four countries in Central and Eastern Europe in relation to clinical benefit.

BACKGROUND: Almost 100 novel cancer medicines have been approved in Europe over the last decade. Limited public health care resources in countries in Central and Eastern Europe (CEE) call for a prioritization of access to effective medicines. We investigated how both reimbursement status and waiting time to reimbursement correlate with the magnitude of clinical benefit provided by novel medicines in four selected countries (Czechia, Hungary, Poland, and Slovakia). MATERIALS AND METHODS: A total of 124 indications of 51 cancer medicines with marketing authorization by the European Medicines Agency in 2011-2020 were included and followed up until 2022. Data on reimbursement status and waiting time to reimbursement (i.e. time from marketing authorization to national reimbursement approval) were collected for each country. Data were analyzed in relation to clinical benefit status (i.e. substantial versus nonsubstantial clinical benefit) of indications according to the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). RESULTS: The degree of reimbursement differed between countries with 64% of indications with reimbursement in Czechia, 40% in Hungary, 51% in Poland, and 19% in Slovakia. In all countries, a significantly greater proportion of indications with a substantial clinical benefit was reimbursed (P < 0.05). The median waiting time to reimbursement ranged from 27 months in Poland to 37 months in Hungary. No significant differences in waiting time in relation to clinical benefit were observed in any country (P = 0.25-0.84). CONCLUSIONS: Cancer medicines with a substantial clinical benefit are more likely to be reimbursed in all four CEE countries. Waiting times to reimbursement are equally long for medicines with or without a substantial clinical benefit, indicating a lack of prioritization of fast access to medicines delivering a substantial benefit. Incorporation of the ESMO-MCBS in reimbursement assessments and decisions could aid in better utilization of limited resources to deliver more effective cancer care.

Access to innovative drugs and the National Reimbursement Drug List in China: Changing dynamics and future trends in pricing and reimbursement.

BACKGROUND AND OBJECTIVES: Multiple reforms aimed at improving the Chinese population's health have been introduced in recent years, including several designed to improve access to innovative drugs. We sought to review current factors affecting access to innovative drugs in China and to anticipate future trends. METHODS: Targeted reviews of published literature and statistics on the Chinese healthcare system, medical insurance and reimbursement processes were conducted, as well as interviews with five Chinese experts involved in the reimbursement of innovative drugs. RESULTS: Drug reimbursement in China is becoming increasingly centralized due to the removal of provincial pathways, the establishment of the National Healthcare Security Administration and the implementation of the National Reimbursement Drug List (NRDL), which is now the main route for drug reimbursement in China. There is also an increasing number of other channels via which patients may access innovative treatments, including various types of commercial insurance and special access. Health technology assessment (HTA) and health economic evidence are becoming pivotal elements of the NRDL decision-making process. Alongside the optimization of HTA decision making, innovative risk-sharing agreements are anticipated to be increasingly leveraged in the future to optimize access to highly specialized technologies and encourage innovation while safeguarding limited healthcare funds. CONCLUSIONS: Drug public reimbursement in China continues to align more closely with approaches widely used in Europe in terms of HTA, health economics and pricing. Centralization of decision-making processes for public reimbursement of innovative drugs allows consistency in assessment and access, which optimizes the improvement of the Chinese population's health.

Time to reimbursement of novel anticancer drugs in Europe: a case study of seven European countries.

BACKGROUND: Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer medicines and explore factors influencing the reimbursement process in seven high-income European countries. MATERIALS AND METHODS: We carried out a retrospective case study of anticancer medicines with European Union Market Access (EU-MA) and a positive Committee for Medicinal Products for Human Use opinion from 2016 until 2021 with subsequent national reimbursement approval (NRA). The National Health Technology Assessment (HTA) and reimbursement websites of Germany, France, UK, the Netherlands, Belgium, Norway and Switzerland were used to identify TTR, defined as time from EU-MA to NRA. Additionally, we investigated medication-, country-, indication- and pharma-related factors potentially influencing TTR. RESULTS: Thirty-five medicines were identified for which TTR ranged from -81 days to 2320 days (median 407 days). At data cut-off, 16 (46%) were reimbursed in all seven countries. Overall, the shortest TTR was in Germany (median 3 days, all medicines reimbursed <5 days). The time limit for reimbursement of 180 days stated by the Council of European Communities after the EU-MA (EU Transparency Directive) was met for 100% of included medicines in Germany, 51% in France, 29% in the UK and the Netherlands, 14% in Switzerland, 6% in Norway and 3% in Belgium. The TTR was significantly different between countries (P < 0.001). In multivariate analysis, factors associated with shorter TTR were higher gross domestic product (GDP), absence of a pre-assessment procedure and submission by a big pharmaceutical company. CONCLUSIONS: TTR of anticancer medicines varies significantly between seven high-income European countries and leads to inequality in access. Among explored medication-, country-, indication- and pharma-related factors we found that a high GDP, the absence of a pre-assessment procedure and submission by big pharmaceutical companies were associated with shorter TTR.

Factors Associated With Adherence to First-line Antiviral Therapy Among Commercially Insured Patients With Chronic Hepatitis B.

Background: Nonadherence to antiviral therapy can lead to poor clinical outcomes among patients with chronic hepatitis B (CHB). We used a claims database to evaluate risk factors for nonadherence to antiviral therapy among commercially insured patients with CHB in the United States. Methods: We obtained data for commercially insured adult patients with CHB prescribed entecavir or tenofovir disoproxil fumarate (TDF) in 2019. Primary outcomes were adherence to entecavir and adherence to TDF. Enrollees with a proportion of days covered (PDC) ≥80% were considered adherent. We presented adjusted odds ratios (AORs) from multivariate logistic regressions. Results: Eighty-three percent (n = 640) of entecavir patients were adherent, and 81% (n = 687) of TDF patients were adherent. Ninety-day supply (vs 30-day supply; AOR, 2.21; P < .01), mixed supply (vs 30-day supply; AOR, 2.19; P = .04), and ever using a mail order pharmacy (AOR, 1.92, P = .03) were associated with adherence to entecavir. Ninety-day supply (vs 30-day supply; AOR, 2.51; P < .01), mixed supply (vs 30-day supply; AOR, 1.82; P = .04), and use of a high-deductible health plan (vs no high-deductible health plan; AOR, 2.29; P = .01) were associated with adherence to TDF. Out-of-pocket spending of >$25 per 30-day supply of TDF was associated with reduced odds of adherence to TDF (vs <$5 per 30-day supply of TDF; AOR, 0.34; P < .01). Conclusions: Ninety-day and mixed-duration supplies of entecavir and TDF were associated with higher fill rates as compared with 30-day supplies among commercially insured patients with CHB.

Lenalidomide Maintenance and Measurable Residual Disease in a Real-World Multiple Myeloma Transplanted Population Receiving Different Treatment Strategies Guided by Access to Novel Drugs in Brazil.

Despite recent advances in multiple myeloma (MM), the incorporation of novel agents and measurable residual disease (MRD) monitoring in low-income countries remains a challenge. Although lenalidomide maintenance (M-Len) after autologous stem cell transplantation (ASCT) has been associated with improved outcomes and MRD has refined the prognosis of complete response (CR) cases, until now, there have been no data on the benefits of these approaches in Latin America. Here, we evaluate the benefits of M-Len and MRD using next-generation flow cytometry (NGF-MRD) at Day + 100 post-ASCT (n = 53). After ASCT, responses were evaluated based on the International Myeloma Working Group criteria and NGF-MRD. MRD was positive in 60% of patients with a median progression-free survival (PFS) of 31 months vs. not reached (NR) for MRD-negative cases (p = 0.05). The patients who received M-Len continuously had a significantly better PFS and overall survival (OS) than those without M-Len (median PFS: NR vs. 29 months, p = 0.007), with progression in 11% vs. 54% of cases after a median follow-up of 34 months, respectively. In a multivariate analysis, MRD status and M-Len therapy emerged as independent predictors of PFS (median PFS of M-Len/MRD- vs. no M-Len/MRD+ of NR vs. 35 months, respectively; p = 0.01). In summary, M-Len was associated with improved survival outcomes in our real-world MM cohort in Brazil, with MRD emerging as a useful reproducible tool to identify patients at an earlier risk of relapse. The inequity in drug access remains a hurdle in countries with financial constraints, with a negative impact on MM survival.

Hypertension Control Cascade and Regional Performance in India: A Repeated Cross-Sectional Analysis (2015-2021).

Background The weak control cascade of hypertension from the time of screening till the attainment of optimal blood pressure (BP) control is a public health challenge, particularly in resource-limited settings. The study objectives were to (1) estimate the change in the rate of prevalence of hypertension, the yield of newly diagnosed cases, initiation of treatment, and attainment of BP control in the age group 15 to 49 years; (2) ascertain the magnitude and predictors of undiagnosed hypertension, lack of initiation of treatment, and poor control of those on antihypertensive therapy; and (3) estimate the regional variation and state-level performance of the hypertension control cascade in India. Methodology We analyzed demographic and health surveillance (DHS) data from India's National Family Health Survey Fifth Series (NFHS-5), 2019-2021, and NFHS-4 (2015-2016). The NFHS-5 sample comprised 695,707 women and 93,267 men in the age group of 15 to 49 years. Multiple logistic regressions were performed to find the associated predictors, and respective adjusted odds ratios (aORs) were reported. Results The prevalence of hypertension (cumulative previously diagnosed and new cases) among individuals aged 15 to 49 years was 22.8% (22.6%, 23.1%; n = 172,532), out of which 52.06% were newly diagnosed cases. In contrast, in NFHS-4, the prevalence of hypertension among individuals aged 15 to 49 years was 20.4% (20.2%, 20.6%; n = 153,384), of which 41.65% were newly diagnosed cases. In NFHS-5, 40.7% (39.8% and 41.6%) of the previously diagnosed cases were on BP-lowering medications compared to 32.6% (31.8%, 33.6%) in NFHS-4. Furthermore, in NFHS-5, controlled BP was observed in 73.7% (72.7% and 74.7%) of the patients on BP-lowering medication compared to 80.8% (80.0%, 81.6%) in NFHS-4. Females compared to males (aOR = 0·72 and 0·007), residents of rural areas (aOR = 0·82 and 0·004), and those belonging to the socially disadvantaged groups were not initiated on treatment despite awareness of their hypertension status indicative of poor treatment-seeking behavior. Furthermore, increasing age (aOR = 0·49, P < 0·001), higher body mass index (aOR = 0·51, P < 0·001), and greater waist-to-hip ratio (aOR = 0·78, P = 0·047) were associated with uncontrolled hypertension in patients on antihypertensive drug therapy. Conclusions Hypertension control cascade in India is largely ineffectual although screening yield and initiation of antihypertensive treatment have improved in NFHS-5 compared to NFHS-4. Identification of high-risk groups for opportunistic screening, implementing community-based screening, strengthening primary care, and sensitizing associated practitioners are urgently warranted.

Developing Prioritization Criteria to Identify Target Drugs for CalRx, the California Generic Drugs Initiative.

OBJECTIVES: This study aimed to establish criteria to identify priority drugs for CalRx, a California-sponsored initiative to support the manufacture and distribution of affordable generic drugs. METHODS: A web-based ranking exercise was implemented with key stakeholders in August 2020, using pricing, spending, and public health criteria identified through a review of academic literature and public health agency reports. A total of 39 of 40 invited stakeholders in 4 different categories-patient advocates, healthcare providers, health insurers, and health policy and economic experts-participated in this study (98% response rate). RESULTS: Drugs that treat large populations, drugs that represent high cost to payors, and drugs that represent high cost to consumers were ranked a priority, receiving > 10% of ranking weights. Drugs that treat conditions with high morbidity or mortality, drugs without therapeutic alternatives, and drugs treating vulnerable populations represented criteria of further interest (9%-10% of weights). Shortage risk and curative effect (8%-9% of the weights), high price increases, communicable disease treatments, and high unit prices (< 8% of the weights) represented the bottom of the priority distribution. CONCLUSIONS: This study suggests that drugs that treat large populations, drugs that represent large costs to payors, and drugs that represent large costs to consumers should be the priority for California's CalRx generic drug initiative. A prioritizing algorithm will assist California in determining top drugs to target from a public health and spending perspective as it plans the rollout of the CalRx initiative and negotiates with drug manufacturers.

[Prospective observational study of the impact of problems accessing treatment such as risk factors for adherence and persistence. Pilot study]. / Estudio observacional prospectivo del impacto de los problemas de acceso al tratamiento como factores de riesgo de la adherencia y persistencia. Estudio piloto.

Introduction: Some preliminary studies that reveal the onset of risk factors not investigated previously in regard to the health system were performed. They can reduce adherence and/or persistence of pharmacological treatments. Knowledge about them can lead to possible solutions. Aim: To estimate the incidence of risk factors in regard to the health system that can reduce adherence/persistence with treatments associated with problems accessing these in the community pharmacy. Method: Transversal, randomized, prospective study in community pharmacies in Asturias and Aragón regions. The primary endpoint was the incidence of new risk factors that means that the prescription is inadequate for its dispensing. Different subgroups were analyzed according to type of risk factor, population and prescription. Results: The typical patient is a vulnerable person according to his age (65.4 years), multipathology and polypharmacy (6.8 drugs). After the evaluation of 138,697 cases of dispensing in 98 community pharmacies a total of 2009 patients were detected with 2221 cases of dispensing with risk factors in terms of adherence and/or persistence (1.6% of the total dispensing). The type of incidence most commonly observed was expiry of the prescription (54.7%; 95%CI=52.6-56.8), followed by no prescription record (18.7%; 95%CI: 17.1-20.3). For its part supply problems stood at 10.2% (95%CI= 10.6%-10.9%). The most compromised therapeutic groups were groups N Nervous System (27.6%), C Cardiovascular System (20.3%) and A Gastrointestinal System (15.3%). Conclusions: The results obtained suggest that the current incidence of risk factors in regard to the health system in terms of adherence and/or persistence may comprise a health problem with a clinical, quality of life and financial impact. As these risk factors are modifiable, a greater capacity for community pharmaceutical action by means of exceptional dispensing to authorize the treatment's continuity would be an acceptable solution.

Barriers in precision medicine implementation among Advanced Nonsquamous Cell Lung Cancer-patients: A Real-World Evidence Scenario.

Background: Precision oncology has a prominent role in nonsquamous non-small cell lung cancer (nsNSCLC) treatment progress; however, its access in a real-world scenario might be limited. Objective: To investigate the time spent in nsNSCLC molecular profile evaluation and its influence on clinical decisions. Methods: nsNSCLC patients who underwent molecular testing in a private referral Brazilian center between November 2015 and February 2020 were identified. The interval from nsNSCLC diagnosis to the characterization of the molecular profile was determined. Other outcomes, focusing on the biomarker tissue journey, were also assessed. Results: In this cohort (n = 78), the median time between the advanced nsNSCLC diagnosis and biomarker characterization was 40.5 days (range, 29.5-68.5). The median interval between the diagnosis and the test request was longer than the interval between the request and the results (respectively 29.0 versus 12.0 days; p < 0.001). At the treatment initiation, 51% (36/71) of the patients who received any systemic therapy did not have their driver mutations panel results available. But on these, 42% (15/36) had a targetable alteration identified later on. Among patients harboring a targetable alteration, only 46% (n = 13/28) received a tyrosine kinase inhibitor (TKI) as first-line therapy. The median time to the TKI initiation was even longer than the median time to all treatment initiation (92.0 versus 40.0 days). Conclusions: Our data show a long median time from advanced nsNSCLC diagnosis and the availability of the biomarker testing in medical practice, which impacted the choice of a non-personalized therapy as the first-line.

Adherence during COVID-19: The role of aging and socio-economics status in shaping drug utilization.

Our study investigates the potential impact that COVID-19 and lockdown restrictions may have had on drug utilization and the role of patient age and education in reshaping it. We focused on patients affected by diabetes mellitus, who are likely to suffer a higher degree of morbidity and mortality due to COVID-19. We used a bi-monthly administrative panel dataset from January 2019 to December 2020 from Liguria (Italy), one of the regions with the highest number of individuals over the age of 65 in Europe. The results demonstrated that, after the initial shock, when patients tried to increase their personal stock of drugs to overcome the risk of possible additional barriers generated by the coronavirus, the hoarding effect almost disappeared. Adherence has drastically reduced during the COVID-19 pandemic and has never reached pre-COVID levels again. Older and poorly educated patients seem to have suffered more from the restrictions imposed by the lockdown and fear of contagion and they may be the ideal target group when considering possible policy interventions to improve adherence.

Emerging Systemic Therapies in Advanced Unresectable Biliary Tract Cancer: Review and Canadian Perspective.

Biliary tract cancer (BTC) is a group of rare and aggressive malignancies with a dismal prognosis. There is currently a significant lack in effective treatment options for BTC, with gemcitabine-cisplatin remaining the first-line standard of care treatment for over a decade. A wave of investigational therapies, including new chemotherapy combinations, immunotherapy, and biomarker-driven targeted therapy have demonstrated promising results in BTC, and there is hope for many of these therapies to be incorporated into the Canadian treatment landscape in the near future. This review discusses the emerging therapies under investigation for BTC and provides a perspective on how they may fit into Canadian practice, with a focus on the barriers to treatment access.

Drug Lag and Associated Factors for Approved Drugs in Korea Compared with the United States.

(1) Background: Drug lag, the delay between the first global regulatory approval and approval by the national health authorities in other countries, impacts the accessibility of drugs. Although the Korean pharmaceutical market has grown significantly, most of its innovative drugs for public health depend on imports from foreign pharmaceutical markets. (2) Methods: We extracted data from the official websites of the Korean Ministry of Food and Drug Safety (MFDS) and the US Food and Drug Administration. Information on new molecule entity drugs, approved as imported drugs by MFDS from 2000 to 2019, was extracted. Multivariate Cox proportional hazard models on drug approval were estimated. (3) Results: In total, 424 drugs were analyzed. Orphan drugs designated by MFDS were less likely to receive approval (HR = 0.731, 95% CI: 0.572-0.934). The drugs with Korean MAHs were less likely to obtain drug approval than those with MAHs of subsidiaries of multinational pharmaceutical companies (HR = 0.524, 95% CI: 0.371-0.738). In the analyses for non-orphan drugs (n = 37), oncology drugs that need local clinical study (HR = 0.247, 95% CI: 0.093-0.657) and drugs that need more patients in a local clinical study (HR = 0.993, 95% CI: 0.988-0.999) were less likely to receive approval, with longer drug lag. The higher number of clinical studies in Korea was associated with a shorter drug lag (HR = 2.133, 95% CI: 1.196-3.805). (4) Conclusions: Our findings imply that Korean pharmaceutical companies should augment their research capabilities for new drug development. Furthermore, consideration of orphan drugs used in rare diseases is needed for drug approval to ensure the availability of these drugs in the market without approval delays.

Health Technology Assessment Process for Oncology Drugs: Impact of CADTH Changes on Public Payer Reimbursement Recommendations.

Public reimbursement systems face the challenge of balancing provision of needed treatments and the reality of limited resources. Canada has a complex system for drug approval and public reimbursement, with jurisdiction divided between the federal government and the provinces/territories. A pivotal role is that of health technology assessment (HTA), which relies primarily on health economic principles to analyze the value of drugs on a population health basis and make recommendations about public reimbursement. The Canadian Agency for Drugs and Technologies in Health (CADTH) provides recommendations to all provinces but Quebec. This article provides an overview of Canada's approval and public reimbursement pathway, including the role of HTA and the economic principles on which it relies. Starting in late 2020, CADTH reduced the cost per quality-adjusted life year (QALY) threshold, the metric relied upon in making recommendations to public payers. An analysis of all 56 oncology drug final recommendations issued from January 2020 to January 2022 was conducted and confirms this reduction in the cost per QALY threshold. As a result of this threshold reduction, recommendations to the provinces include, in a number of cases, substantially greater price reductions. The potential implications for successful price negotiation with the pan-Canadian Pharmaceutical Alliance (pCPA), the public negotiating body for the provinces, are discussed.