Reimbursement Approval Research Articles

The Effects of Removing the Requirement for Prior Reimbursement Approval on Anticoagulant Use in Ireland: A Cross-Sectional Study.

Prior approval for reimbursement is a policy of cost containment while ensuring oversight and governance of medicines. It has been employed in Ireland to address financial challenges due to the shift from warfarin to direct oral anticoagulants (DOACs). Studies assessing the effectiveness of this policy are limited. Thus, we aimed to examine the effectiveness of prior approval for reimbursement of DOACs (apixaban, rivaroxaban) as a cost containment policy in Ireland. The Irish Health Service Executive-Primary Care Reimbursement Service database was used in this cross-sectional study. We examined the prescribing frequencies and associated costs of the oral anticoagulants; [(OACs) apixaban, rivaroxaban and warfarin] listed in the top 100 most frequently prescribed drugs, between 2018 and 2021. Time series negative binomial regression was used to assess the impact of removing the approval requirement of apixaban in September 2019 followed by the other DOACs in November 2020. The prescribing frequency of OACs increased by almost 20% from 2018 to 2021. This study showed there were significant differences in the proportion of OACs prescribed among the Community Drug Schemes. A statistically significant decreased use of apixaban (< 1%, p < 0.05) occurred when prior approval was removed for all DOACs. The removal of prior approval for reimbursement of DOACs in Ireland had a minimal impact on the prescribing frequency trends of the OACs. Future use of these potentially useful policies by healthcare systems requires careful consideration of drug type, approval criteria and length of time the policy remains in place to minimise any negative effects associated with their use.

The use of telehealth in a large community oncology practice prior to and during the COVID-19 pandemic.

1631 Background:The COVID-19 pandemic prompted implementation of telehealth services in oncology following CMS approval for reimbursement. Using data from a single large US-based community oncology practice, we characterized the adoption of telehealth, evaluated telehealth’s impact on patient transit to the site of care, and the frequency of ER visits and hospitalizations. Methods: A retrospective cohort analysis was conducted using data from January 2019 through June 2022 from the FCS EMR database, IQSS’s RefineIQ database, which captures and standardizes patient treatments for consistent analysis, InfoDive, a reimbursement platform with data on clinic visits, and Oncology Care Model data. The target population included all patients with cancer aged 18 or older under active management at FCS during the study window with at least 60 days of follow-up. Patient disease and demographic characteristics and ER/hospital care visits were compared between telehealth groups, as well as impact of telehealth use on transit time and distance traveled for patients was summarized using descriptive statistics. Results:178,531 patients were analyzed. Median age was 68, with 64% female and 47% white. 97% of patients lived in a metropolitan area, 97% in Florida, and 77% in areas with less than $78,000 median income. Median duration of disease was 41 months, 24% of patients were stage IV and 93% ECOG 0-1. 20% of patients used telehealth, with 81% having only one telehealth use per year. Patients using telehealth, compared to those that did not, were more likely to be white (50% vs 46%), have commercial insurance (30% vs 27%), live in areas where annual median income was &gt; $78,000 (25% vs 22%) and ≥95% of the population graduated high school (31% vs 26%). Telehealth saved a median of 5 miles driven per user annually. Users tended to have more advanced disease than non-users, with a higher proportion of metastatic disease (27% vs 23%), high CMS risk score (16% vs 15%), and line of therapy 2 or greater (10% vs 7%). Users had higher median annual oncology clinic visits both pre- (5 vs 3) and post-telehealth approval (6 vs 5). Hospital admissions after ER visits were more frequent among users both pre- (14% vs 13%) and post-telehealth approval (29% vs 25%). Conclusions: Telehealth was somewhat more likely to be used by patients with cancer in more affluent communities, white patients, patients who had more advanced disease and more frequent clinic and hospital visits. Most patients who used telehealth used it only once, and the low utilization of telehealth had limited impact on patient transit effort to the clinic. This study is limited by its concentration at a single large practice in Florida, the relatively low use of telehealth, retrospective design, and selection bias, as the telehealth population had more advanced disease and likely needed more frequent intervention.

Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland

ObjectivesCalcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. MethodsData were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. ResultsBetween September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. ConclusionsThis study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest.

Pediatric Market Access: A Qualitative Study.

This qualitative study aims to analyze current PM regulation and market access requirements and proposes potential solutions to mitigate current challenges. Twenty-two semi-structured interviews were conducted with experts from pharmaceutical industry, regulatory authorities, national health technology assessment (HTA) bodies, pediatricians, and academia from the Netherlands (NL), Germany (DE), the United Kingdom (UK), and France (FR) to get insight into the pediatric research, the regulatory and reimbursement processes, challenges, and solutions. Themes for further testing were developed on how to facilitate pediatric market access. Atlas.ti 9 was used to analyze the findings. Heterogeneity in requirements for the European Medicines Agency (EMA) and HTA approvals are noted. By example, DE grants direct reimbursement after regulatory approval, the other countries require additional reimbursement which generate delays and challenges in patient access after marketing authorization. Key components in facilitating PM market access include multi-stakeholder collaboration, transparency, patient representatives, informed consent guidance, real-world evidence, and appropriate clinical trial designs. Pricing models based on the economic capabilities of individual countries could further reduce delays and challenges in market access. The additional specific pediatric incentives should be taken as best practice to encourage innovation in pediatric conditions. This study highlights differences in requirements for regulatory and reimbursement approval, along with international differences in pricing and reimbursement procedures for pediatric market access.

PP152 Evaluation Of Reimbursement Periods In The Turkish Biosimilar Product Market (1995-2022)

IntroductionBiosimilar products that would enhance the patient’s access to treatments have emerged as a product group that is becoming more widespread globally. Since Turkiye is an emerging market in the pharmaceutical area in the Middle East and North Africa region, and being a reference country in pricing processes for some countries, the number of products in the market and reimbursement decisions are important. The aim of this study is to evaluate duration of inclusion of biosimilars into reimbursement lists after registration in Turkiye.MethodsThis study used website-based information (Turkish Medicine and Medical Devices Agency Registered Products List and Detailed Pharmaceutical Price List, Social Security Institution Reimbursed Product List) to analyze the reimbursement approval duration for registered biosimilars in Turkiye after receiving registration approval. A study has been conducted on the launch period of biosimilar products to patients access with reimbursement and the evaluation period of reimbursement applications after registration approval. Even though they might not be active on the reimbursement list right now, products that have previously been approved for payment have been included.ResultsBetween 1995-2022, biosimilars of 13 active substances in total were registered by the Ministry of Health in Turkiye. Thirty-three different brands and 105 biosimilars with all pharmaceutical forms are registered. As of November 2022, 72 biosimilars were in the reimbursement list. Twenty-two of reimbursed biosimilars were deactivated or excluded from reimbursement. It is calculated that the average evaluation and approval timeline for reimbursement of biosimilars between 2009 and 2022 is 9 months. When biosimilars in the European Medicines Agency (EMA) and Turkiye are compared, 13 biosimilar active substances are licensed in Turkiye compared to 19 for the EMA. When the total number of brands is compared, it has been observed that while 33 brands are registered in Turkiye, this number is 73 for the EMA.ConclusionsThis study, in which reimbursement approval dates for registered biosimilars in Turkiye have been compared based on years and access timelines of biotechnological products, shows that biosimilars have been launched to patients access with reimbursement much faster than biotechnological products.

Réducteur de sinus coronaire : revue de littérature et enjeux autour du registre France Reducer

Coronary sinus Reducer implantation is a percutaneous technique used to treat patients suffering from refractory angina pectoris. The device narrows the coronary sinus, increases the back pressure in the myocardial venous system and forces redistribution of coronary blood flow from less ischemic subepicardium to the more ischemic subendocardium. Multiple clinical studies had proven its efficacy to alleviate myocardial ischemia and related symptoms, and to improve the quality of life of patients with refractory symptomatic chronic coronary artery disease for whom coronary revascularization is deemed unsuitable. This literature review aims to expose the device design, its mechanisms of action, and the clinical data supporting its use.Since November 2021 Reducer's reimbursement has been granted in France by the national health authority. It is the first device to be approved under a newly established reimbursement approval process. A transitional coverage is provided with opportunities for renewal before applying for full-time reimbursement. To fulfill the requirements of the National Commission for Evaluation of Medical Devices and Health Technologies, the French Society of Cardiology has been creating the France Reducer registry. This clinical registry has been collecting data from patients undergoing coronary sinus Reducer implantation regarding their clinical situation, periprocedural information, and one-year follow-up. It is crucial for the future of this emerging therapeutic option in France. To date, 215 patients from 28 centers have been included between June 2022 and September 2023.

Analysing criteria for price and reimbursement of orphan drugs in Spain

ObjectiveThere are differences between countries regarding data requirements for orphan drug evaluation and it is also unknown which criteria might determine the price and reimbursement decision. This study aimed to identify the key criteria for price and reimbursement of orphan drugs in Spain, approved by the European Commission, between January 2012 and June 2018. MethodA descriptive analysis of the orphan drugs and its characteristics was performed. Outcomes criteria assessed were: therapeutic area, existence of alternative treatment, rarity of the disease, clinical trial outcomes and therapeutic positioning report assessment. Hypotheses for each variable regarding Spanish pricing and reimbursement were made and tested with two regression analyses. ResultsOut of 78 orphan drugs approved by the European Commission, 82.1% asked pricing and reimbursement in Spain. From this, 43.8% had pricing and reimbursement approved and 20.3% rejected. Mean time from Spanish marketing authorisation approval to pricing and reimbursement approval was 12.1 ± 5.1 months. Having a positive therapeutic positioning report and no therapeutic alternatives would be associated with a positive pricing and reimbursement in Spain. ConclusionsIt remains challenging to establish which are the driving criteria for pricing and reimbursement approval of orphan drugs in Spain. Further research should be done including other variables that might influence the pricing and reimbursement final decision in Spain.

Two-Year Results on Real-World Fenestrated or Branched Endovascular Repair for Complex Aortic Abdominal Aneurysm in France.

To describe and compare mid-term outcomes from 2 real-world data collection efforts on fenestrated and branched endovascular aortic repair (fbEVAR) for complex abdominal aortic aneurysms (AAAs) in France and to evaluate the potential of health care databases for long-term post-market surveillance (PMS) and continued reimbursement approval. Two real-world studies were conducted in France: a retrospective health care database study (SNDS) and a prospective clinical study. In the SNDS study, data from implantation and/or hospital stays occurring during follow-up were extracted for all patients treated with the study devices from April 2012 to December 2018. In the clinical study, high-risk patients undergoing fbEVAR with the study devices were enrolled consecutively at 15 sites in France from December 2016 to November 2018. Data from 1073 patients were extracted from SNDS and compared with analogous variables from 186 patients in the clinical study. Most demographic details were similar between studies (SNDS vs clinical: mean age, 71.9 vs 71.8 years; men, 91.0% vs 89.8%), as was 30-day mortality (SNDS: 5.5%, clinical: 4.3%). Patients received custom-made fenestrated or branched devices (SNDS: 80.7%, clinical: 96.2%) or CE-marked Zenith Fenestrated devices (SNDS: 19.3%, clinical: 3.8%). Initial or technical success was above 94% for both studies. Two-year freedom from all-cause mortality was 80.0% (SNDS) and 85.1% (clinical study). Two-year freedom from aneurysm-related mortality was 93.8% (SNDS) and 94.6% (clinical study). Detailed imaging outcomes were not captured within SNDS; however, information on secondary procedures to restore patency was available and used as a surrogate measure for secondary interventions. Two-year freedom from secondary interventions was 73% for the SNDS study. In the clinical study, at 2 years, aneurysm stability or shrinkage was observed in 92.3% of patients, freedom from target vessel primary patency loss was above 95% for all visceral target vessels, and freedom from secondary interventions was 79.1%. Real-world outcomes from the SNDS and clinical study suggest positive mid-term outcomes in high-risk populations following fbEVAR for complex AAAs. The similarities between these studies suggest that the use of health care databases may be an alternative to prospective clinical studies for long-term follow-up and PMS. Positive results following endovascular repair of complex abdominal aortic aneurysms are observed from data extracted from both the French health care database and a post-market clinical study despite initial high-risk patient status and diverse center experience. These outcomes parallel more rigorously designed studies and suggest that with careful study design, real-world data collections have high translatable value to add to the clinical understanding of fenestrated and branched endovascular aortic repair (fbEVAR).

Self-reports by persons with multiple sclerosis are an adequate surrogate for healthcare provider data on disease-modifying therapy and multiple sclerosis type

IntroductionSelf-reports are a valuable and cost-effective method of data collection, though they can be influenced by bias. Limited evidence exists on the quality of self-reports by persons with multiple sclerosis (pwMS), particularly since more potent disease-modifying therapies (DMTs) have been introduced. This study aimed to assess the reliability and validity of self-reported DMT use and multiple sclerosis (MS) type in the Swiss Multiple Sclerosis Registry (SMSR) by comparing self-reports with reimbursement approval requests from the Swiss Association for Joint Tasks of Health Insurers. MethodsThe self-reported and reimbursement approval data were linked using privacy-preserving methods based on information available in both databases, i.e., date of birth, canton of residence, sex, and year of MS diagnosis. The SMSR baseline questionnaire data was utilized for the main analysis, while the SMSR follow-up survey data was utilized for the sensitivity analysis. For both analyses, we compared self-reported data with reimbursement approval data that corresponded to the respective periods of the SMSR data collection. Thus, the main analysis included the entirety of the data over the six-year period, while the sensitivity analysis captured a more recent snapshot of the data. To assess reliability, we estimated agreement using Cohen's kappa, and for validity, we estimated accuracy parameters using reimbursement approvals as the reference standard. Univariable and multivariable logistic regression models were employed to investigate factors associated with discordance between self-reports and reimbursement approvals in the main analysis. ResultsThe main analysis included 446 participants, and the sensitivity analysis included 193 participants. The agreement between self-reported and reimbursement approval data for medication use was near-perfect in both analyses (κ = 0.87, 95% confidence interval (CI) 0.85, 0.90 and κ = 0.82, 95% CI 0.76, 0.88). However, the agreement between self-reported and reimbursement approval-documented MS types ranged from fair to moderate (κ = 0.37, 95% CI 0.25, 0.48 to κ = 0.61, 95% CI 0.46, 0.77). The accuracy estimates for self-reported DMT use were generally high (≥ 0.80) with narrow CIs, except for less frequently reported drugs. While the sensitivity and specificity for RRMS were high, there was a notable possibility of false-negative self-reports for RRMS (NPV = 0.33, 95% CI 0.22, 0.45), and false-positive reports for SPMS (PPV = 0.36, 95% CI 0.21, 0.54). Multivariable logistic regression models showed that age (OR = 1.07, 95% CI 1.04, 1.10 per year) and education level (OR = 0.27, 95% CI 0.11, 0.65) were associated with discordance in reported and documented MS types, whereas possession of Swiss citizenship (OR = 0.32, 95% CI 0.14, 0.72) was associated with discordance in DMT use. ConclusionSelf-reported DMT use in pwMS is a reliable and valid information source, with near-perfect agreement and high accuracy. Self-reported MS types showed fair to moderate agreement and varying accuracy, likely reflecting the complexity of diagnosing progressive forms of MS and access to DMTs. In population-based MS research, self-reports of MS types, and particularly DMT use, can serve as a suitable surrogate for healthcare provider data.

Cancer Drugs Reimbursed with Limited Evidence on Overall Survival and Quality of Life: Do Follow-Up Studies Confirm Patient Benefits?

Cancer drug costs have increased considerably within healthcare systems, but many drugs lack quality-of-life (QoL) and overall survival (OS) data at the time of reimbursement approval. This study aimed to review the extent of subsequent literature documenting improvements in OS and QoL for cancer drug indications where no such evidence existed at the time of reimbursement approval. Drug indications with claims of added therapeutical value but a lack of evidence on OS and QoL that were reimbursed between 2010 and 2020 in Sweden were included for review. Searches were conducted in PubMed and ClinicalTrial.gov for randomized controlled trials examining OS and QoL. Of the 22 included drug indications, seven were found to have at least one trial with conclusive evidence of improvements in OS or QoL after a mean follow-up of 6.6 years. The remaining 15 drug indications either lacked subsequent randomized controlled trial data on OS or QoL (n = 6) or showed no statistically significant improvements (n = 9). Only one drug demonstrated evidence of improvement in both OS and QoL for its indication. A considerable share of reimbursed cancer drug indications continue to lack evidence of improvement in both OS and QoL. With limited healthcare resources and an increasing cancer burden, third-party payers have strong incentives to require additional post-reimbursement data to confirm any improvements in OS and QoL.

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

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). 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). 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). 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.

HPR55 Market Access Trends of Pharmaceutical Products in US, EU4 and UK (2016-2021)

To examine trends in the time between regulatory approval and launch/pricing and reimbursement approval in the EU4, UK and US

Is access to adjuvant treatments prioritized over therapies for metastatic cancer? The Israeli experience.

e18599 Background: The Israeli National Insurance Law determines a uniform benefits package ('the Health Basket') for all residents. A public committee advises each year on which new medications should be added to the Health Basket, subject to the fixed annum budget allocated by the government for this purpose. The clinical benefit of the proposed health technologies is the committee's prime consideration; however, the committee also considers the professional medical societies' prioritizations, the expected budget impact, and other social and ethical aspects. Towards the annual discussions for 2023, 63 new indications for 41 cancer drugs were proposed for the annual update. Of those, 8 were for novel neo-adjuvant/ adjuvant indications, all given high priority ranks by the Israeli Oncologists Society based on the significant disease-free survival (DFS) figures from the phase III clinical trials. Varying the adjuvant treatment practice patterns based solely on DFS figures without available overall survival (OS) data has been in much debate recently between global key opinion leaders. We, therefore, aimed to evaluate whether the Israeli decision-makers have de-facto accepted the attitude of prioritizing budgets for adjuvant/neo-adjuvant therapies as the Israeli Oncologists Society recommended. Methods: We collected data on all cancer therapies proposed for inclusion in the 2023 Health Basket update; drug name, indication, treatment setting (curative intent vs. metastatic disease therapy), ESMO-MCBS grade, and whether or not accepted for reimbursement. All data were extracted from the official Israeli Ministry of Health website publications and press releases. Results: 20% of the allocated budget for updating the National Health basket for 2023 was provided to treat solid tumor cancers. 7 out of the 8 candidate therapies in the neo-adjuvant/adjuvant settings received reimbursement approval (88%) vs. 11 out of 55 therapies for advanced/ metastatic stages of disease (20%). 13 of the 16 candidate metastatic disease therapies that had a high ESMO-MCBS score (4 or 5) were not approved for reimbursement in the 2023 annual committee discussions. Conclusions: Our retrospective evaluation of the Israeli reimbursement prioritization process reveals that decision-makers have accepted the approach of prioritizing potentially curative adjuvant therapies over treatments for patients with incurable cancer. In an era of prosperity of adjuvant therapies in a range of tumor types, concerns might arise regarding restrictions on access to novel therapies for metastatic cancer, even those with proven benefits of significantly improving patients' OS and quality of life. Future analysis should determine the impact of this trend adopted by decision-makers in Israel on disease progression and overall survival in the real-world setting.

EE495 Cost-Effectiveness of Pembrolizumab + Axitinib Versus Nivolumab + Ipilimumab As First-Line Treatment of Advanced Renal Cell Carcinoma in the Private Healthcare System in Brazil

In Brazil's Private Healthcare System, intravenous (IV) oncological drugs approved by the regulatory agency are automatically reimbursed. However, when the treatment involves an oral drug, it must go through the health technology assessment (HTA) process for reimbursement approval. In this context, we conducted a study to evaluate the cost-effectiveness of pembrolizumab (IV) + axitinib (oral) versus nivolumab (IV) + ipilimumab (IV) as first-line treatments in patients with advanced renal cell carcinoma (aRCC) at intermediate/poor IMDC (International Metastatic RCC Database Consortium) risk.

Early access programs for medicines: comparative analysis among France, Italy, Spain, and UK and focus on the Italian case

Early access programs (EAPs) generally refer to patient access to medicines/indications before marketing authorization, possibly extended to price and reimbursement approval. These programs include compassionate use, which is usually covered by pharmaceutical companies, and EAPs reimbursed by third-party payers. This paper aims at comparing EAPs in four European countries (France, Italy, Spain, UK) and providing empirical evidence on EAPs in Italy. The comparative analysis was conducted through a literature review (including scientific and grey literature), complemented by 30-min semi-structured interviews with local experts. The Italian empirical analysis employed data available on the National Medicines Agency website. Although EAPs are very different across countries, they exhibit some common features: (i) eligibility criteria refer to the absence of valid therapeutic alternatives and a presumed favourable risk–benefit profile; (ii) payers do not allocate a pre-determined budget to these programs; (iii) total spending on EAPs is unknown. The French EAPs seem to be the most structured, financed through social insurance, covering pre-marketing, post-marketing and pre-reimbursement phases and providing for data collection. Italy’s approach to EAPs has been varied, with several programs covered by different payers, including the cohort-based 648 List (for both early access and off-label use), the nominal-based 5% Fund, and Compassionate Use. Most applications to EAPs are from the Antineoplastic and immunomodulating drug class (ATC L). Some 62% of indications in the 648 List are either not under clinical development or have never been approved (pure off-label use). For those subsequently approved, most approved indications coincide with those covered through EAPs. Only the 5% Fund provides data on economic impact (€ 81.2 million in 2021; average cost per patient € 61.5K). Diverse EAPs are a possible source of inequalities in access to medicines across Europe. A harmonization of these programs, though difficult to achieve, could be modelled on the French EAPs and provide key advantages, not least of which a common effort to collect real-world data in parallel with clinical trials and clear separation between EAPs and off-label use programs.

502 The effects of removing the requirement for prior reimbursement approval on anticoagulant use in Ireland: A cross sectional study

Abstract Introduction Prior approval for reimbursement is a cost containment policy, aimed at reducing demand (1). It has been used temporarily in the Irish Healthcare system to deal with the initial financial challenges posed by the shift in use towards the Direct Oral Anticoagulants (DOACs) (apixaban, rivaroxaban, edoxaban and dabigatran) from warfarin. Improved safety of DOACs use was a secondary aim of this policy. The use of prior approval policies is increasing in Ireland but studies assessing their effectiveness are limited. Aim To examine the effect of removing the cost containment policy of prior approval for reimbursement of apixaban and rivaroxaban using a national pharmacy claims database. Methods The Health Service Executive-Primary Care Reimbursement Service database in Ireland was used in this cross-sectional study. The prescribing frequencies and associated costs of the oral anticoagulants; ((OACs) apixaban, rivaroxaban, and warfarin) listed in the top 100 most frequently prescribed drugs on the Community Drug Schemes (CDS), between 2018 and 2021 were examined. Levothyroxine was used as a negative control to detect any external deviances in the prescribing data records. Interrupted time series Poisson regression was used to assess the impact of removing the approval requirement of apixaban in September 2019 followed by the other DOACs in November 2020. Results The prescribing frequency of OACs increased by almost 20% during the study period. Figure1 shows the prescribing frequencies of apixaban , rivaroxaban , warfarin and levothyroxine on each of the three community drug schemes – General medical scheme (GMS), Drug payments scheme (DPS) and Long term illness scheme (LTI) during the study period.Timelines at September 2019 and November 2020 show the removal of prior approval for apixaban and all DOACs respectively. This study showed there were significant differences in the proportion of OACs prescribed among the CDS. A statistically significant decreased use of apixaban (&amp;lt;1%, p&amp;lt;0.05) occurred when prior approval was removed for all DOACs. Conclusion The removal of prior approval for reimbursement of DOACs in Ireland had a minimal impact on the prescribing frequency trends of the OACs. Future use of these potentially useful policies by healthcare systems requires careful consideration of drug type, approval criteria and length of time the policy remains in place.

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

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. 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. 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. 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.

Is het chinolonengebruik in België gedaald door de gewijzigde terugbetalingsvoorwaarden van 2018?

Has the use of quinolones in Belgium decreased due to the introduction of reimbursement conditions in 2018? The substantial adverse drug reactions and contribution to antimicrobial resistance of quinolones implore public health initiatives to restrict the usage of these antibiotics. One such initiative in Belgium was to only reimburse quinolones under stringent conditions from May 2018 onwards. In this article, the authors aim to assess the effectiveness of this policy by charting the evolution of quinolone use. This study is based on reimbursement data of quinolones delivered to members of the Christian health insurance fund (CM) in public pharmacies from May 1, 2016 to April 30, 2021. The variables of interest are the number of users and the volume in defined daily dose (DDD). Diagnostic data about members with approval for reimbursement were obtained from the database of the CM, containing authorisations of reimbursement. 19% to 28% of the authorisations were justified as ‘exceptional’ situations without any specific diagnosis. The number of users of reimbursed quinolones decreased by 75% immediately after the implementation of the policy, although a decrease of only 36% was observed in the overall use of quinolones (reconstructed by means of statistics provided by the Belgian society of public pharmacists (APB)). The reimbursement policy in 2018 induced a substantial decrease (75%) in the use of reimbursed quinolones, but also a considerable increase in the use of non-reimbursed quinolones. Although the overall use still has decreased remarkably (36%) since the policy, the decrease was insufficient to reduce the use of quinolones to the objective of 5% of all prescribed antibiotics. In order to keep the quinolone use within reasonable bounds, the authors encourage education of health practitioners, dialogue between medical actors and sensibilisation of users. In addition, this study draws attention to the need for publicly available data on both reimbursed and non-reimbursed medication.

Leveraging ambulatory care pharmacist expertise in medication appeals to overcome access barriers: A descriptive report

AbstractIntroductionPrescription prior authorization (PA) and prohibitive out‐of‐pocket costs are encountered across all specialties of care. These barriers are burdensome for prescribers and patients due to the multiple steps required to gain approval for payer reimbursement for medications.ObjectivesThe primary objective was to characterize clinical pharmacist impact on medication appeals and high cost resolution.MethodsThis was a retrospective review of medication access intervention data collected from January 1, 2021, through July 31, 2021, at an academic medical center where five clinical pharmacists are embedded across 11 specialty and family medicine clinics. Intervention data was documented for both specialty and nonspecialty prescriptions. The primary end point quantified and characterized interventions based on access issues, defined as insurance denial or high out‐of‐pocket cost. Additional end points included time to appeal determination, total time spent on appeal activities, the incidence of denials, duration of the interruption, and assistance dollars secured for cost‐related barriers.ResultsOver the 7‐mo period, there were 531 prescriptions identified for clinical pharmacist access intervention. Of the total interventions collected, 42% (n = 221) were appeals for insurance denials and 58% (n = 310) addressed high out‐of‐pocket cost. The approval rate of appeals was 94% (n = 208). The majority of appeals (89%) were submitted within 3 d. The median time to appeal determination was five calendar days. The estimated time spent on appeal activities by the clinical pharmacists was 6.8 work wk. There were 51 patients of therapy interruption. The total assistance dollars secured for high out‐of‐pocket costs reached an estimated $1 953 200 over the report period.ConclusionThis report characterizes an approach to effectively manage medication appeals and cost resolution through embedded clinical pharmacists. Leveraging embedded pharmacists' clinical knowledge and familiarity with payer processes in medication appeals achieved a 94% approval rate. The current payer process places a burden disproportionately on prescribers and patients, delaying or preventing medication access.

Abstract 5963: A framework for extrapolating evidence for molecularly targeted therapies from common to rare cancers - bridging the gap

Abstract BACKGROUND: Advances in understanding of potentially targetable molecular pathways driving carcinogenesis coupled with rapid development of tumor profiling technologies are partitioning cancers into rare biomarker-defined diseases. Assessing biomarker-targeted therapies within these small populations in adequately powered randomized trials is becoming unfeasible, leading to reliance on lower quality evidence from uncontrolled studies using unvalidated surrogate outcomes. When robust evidence for a targeted therapy being considered already exists in common cancers, this evidence may potentially be extrapolated to support the use of this therapy in rare cancers sharing the same biomarker and reduce additional evidence requirements for regulatory or reimbursement approval. However, extrapolation may not be appropriate in some settings due to biological differences between cancer types. METHODS: Building on recommendations for core components of extrapolation identified from a scoping review of methodological guidance, we constructed a framework proposing criteria for extrapolating evidence for targeted therapies from common to rare cancers. RESULTS: Criteria reflect key assumptions of disease similarity when defined by the biomarker and similarity of treatment response. Criteria are judged under five extrapolation components: (1) Analytical validity of the test used to identify the biomarker and criteria used to define biomarker status in the rare cancer, (2) Strength of evidence supporting biomarker actionability in the rare cancer and evidence that actionability may differ from the common cancer, (3) Quantitative estimation of the natural history of the biomarker-defined rare cancer as control group, (4) Validity of surrogate endpoints used to extrapolate treatment effect from the common cancer and predictions of clinical benefit in the rare cancer, and (5) Similarity of the safety profile between cancers and methods to augment safety data in the rare cancer. Using these criteria, decision-makers can judge whether sufficient evidence exists to support extrapolation or identify specific knowledge gaps to better target further research to be able to judge whether extrapolation is appropriate or not. Residual uncertainties for fulfilling criteria can also define post-approval commitments. CONCLUSIONS: We outline a pragmatic and systematic approach for selecting and evaluating existing evidence to judge when extrapolation is appropriate. This framework can be used to promote standardized, comprehensive, and transparent decision-making and facilitate discussion between stakeholders in drug development and clinical guideline and health technology assessment groups. Citation Format: Doah Cho, Sarah J. Lord, John R. Simes, Wendy Cooper, Saskia Cheyne, Chee Khoon Lee. A framework for extrapolating evidence for molecularly targeted therapies from common to rare cancers - bridging the gap [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5963.