Surrogate endpoints in assessment of clinical efficacy and safety of oncology drugs — analysis of AHTAPol recommendations

Terapie stosowane w onkologii oceniane są pod względem skuteczności i bezpieczeństwa zarówno na etapie decyzji terapeutycznych podejmowanych przez lekarzy, jak i na etapie procesów refundacyjnych (m.in. przez Agencję Oceny Technologii Medycznych). Oceny te polegają głównie na analizie korzyści mierzonych za pomocą punktów końcowych dotyczących progresji (progression free survival — PFS, time to progression — TTP) oraz przeżywalności (overall survival — OS). Decyzje kliniczne w onkologii w codziennej praktyce podejmuje się najczęściej na podstawie zastępczych punktów końcowych, tzw. surogatów (PFS, TTP, odpowiedź na leczenie, częściowa odpowiedź na leczenie itp.), w odróżnieniu od istotnych dla pacjenta punktów końcowych (OS). Wynika to z faktu, iż ocena przeżywalności często wiąże się z koniecznością przeprowadzenia wieloletnich badań w relatywnie dużych grupach pacjentów, co nie zawsze jest praktycznie możliwe. Wobec powyższego pojawia się pytanie, czy i jak bardzo surogaty są skorelowane z punktami takimi jak przeżywalność. Rozważane punkty końcowe mają różne znaczenie kliniczne, różną istotność dla pacjentów, a także w różnym stopniu przyczyniają się do decyzji o finansowaniu terapii ze środków publicznych. Celem niniejszej pracy było przedstawienie podstawowych definicji związanych z najczęściej stosowanymi punktami końcowymi w onkologii, wskazanie podobieństw i różnic między nimi, które mogą potencjalnie wpływać na wnioskowanie, a także przeanalizowanie wpływu tych punktów końcowych na rekomendacje dotyczące finansowania terapii onkologicznych ze środków publicznych.Treatments in oncology are assessed in terms of clinical efficacy and safety at the stage of therapeutic decisions made by oncologists, but also during reimbursement processes (by Health Technology Assessment bodies). Those assessments are based on analysis of clinical benefits measured by progression-related endpoints (progression free survival — PFS, time to progression — TTP) or by survival (overall survival — OS). Therapeutic decisions in clinical practice are usually based on so called surrogate endpoints (PFS, TTP, response rate, partial response rate), as opposed to „hard” endpoints like survival (OS). This results from a fact that it is much harder to prove survival benefits in clinical trials, because it usually requires long-term follow-up studies and large numer of enrolled patients. This raises a question of whether surrogates are correlated with hard clinical enpoints, and how strong the correlation is. All those endpoints have different clinical meaning, different significance for patients and also different impact on reimbursement decisions. The aim of this paper was to present definitions of the most commonly used oncology endpoints, show differences and similarities between them and to analyze what is their impact on reimbursement recommendations made by Polish Agency for Health Technology Assessment

Economic and social cost of epilepsy in Poland : 5-year analysis

Introduction: Epilepsy affects nearly 50 million people around the world. As a common and chronic disease generates a high cost burden for healthcare system and patients. Aim: We aimed to determine the most current direct and indirect costs of epilepsy in Poland from the social perspective for the years 2014–2018, to analyze the changes of expenditures over time, indicate trends and to determine key cost-drivers. Material and Methods: Direct and indirect costs using a top-down approach were estimated based on the public institutions' data for the ICD-10 codes G40 and G41. Direct costs included pharmacotherapy, hospitalizations, outpatient specialist care and rehabilitation. A human capital approach was used to estimate loss of productivity due to sick leaves and long-term inability to work. Results: Annual total direct and indirect costs related to epilepsy accounted for EUR 410 million in 2014 and decreased in subsequent years to EUR 361 million in 2018. The indirect costs were dominant (76–83% of total costs) and in the majority related to the long-term absenteeism (87–92% of total indirect costs). In 2014–2018, patients with epilepsy generated EUR 341 million to EUR 282 million of indirect costs. Annual direct costs for patients with epilepsy were EUR 69 million in 2014 and increased to EUR 80 million in 2018. The biggest expenses were the costs of drugs (> 50%) and hospitalizations (~ 40%). Conclusions: Epilepsy is an expensive disorder in terms of consumption of resources and social costs. Decision-makers should take it under special consideration

Policies for biosimilar uptake in Europe: an overview

Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe.status: publishe

Policies for biosimilar uptake in Europe: An overview

markdownabstract__Background__ Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. __Objectives__ The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. __Methods__ An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. __Results__ In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. __Conclusions__ Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market

Policies for biosimilars in different countries in Europe (April 2017).

<p>Policies for biosimilars in different countries in Europe (April 2017).</p

The current situation regarding long-acting insulin analogues including biosimilars among african, Asian, European, and South American countries : findings and implications for the future

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities