A proposed analytical framework for qualitative evaluation of access to medicines from a health systems perspective.

OBJECTIVE: Despite global recognition that access to medicines is shaped by various interacting processes within a health system, a suitable analytical framework for identifying barriers and facilitators from a system's perspective was needed. We propose a framework specifically designed to find drivers to access to medicines from a country's health system perspective. This framework could enable the systematic evaluation of access across countries, disease areas and populations and facilitate targeted policy development. This framework is the byproduct of a larger study on the barriers and facilitators to childhood oncology medicines in South Africa. RESULTS: Eight core (pharmaceutical) functional processes were identified from existing frameworks: (I) medicine regulation, (II) public financing and pricing, (III) selection, (IV) reimbursement, (V) procurement and supply, (VI) healthcare delivery, (VII) dispensing and (VIII) use. National contextual components included policy and legislation and health information systems. To emphasize the interlinkage of processes, the proposed framework was structured as a pharmaceutical value chain. This framework focusses on national processes that are within a country's control as opposed to global factors, and functional mechanisms versus a country's performance or policy objectives. Further refinement and validation of the framework following application in other contexts is encouraged.

The caregiver's experience of childhood cancer treatment in South Africa.

Background: This study explored the treatment-related, financial and psychological experiences of caregivers during cancer treatment of their children in South Africa's (SA) public and private sectors. Methods: In this exploratory study, three focus groups were conducted with caregivers of children undergoing cancer treatment in SA's public healthcare sector. A fourth small focus group with two parents in the private sector was conducted online. A mixed-methods approach was employed using a combination of thematic analysis and grounded theory. Results: Of the 20 public sector caregivers, many expressed frustration at the number of visits to primary healthcare clinics before being referred. Caregivers had difficulties coping with and accepting the diagnosis, alongside managing continued care for the child and other children at home. Support received by family and community members was varied. Financial strain was an important concern. The two private sector parents indicated greater levels of support and no financial hardship, but expressed similar levels of emotional stress. Conclusion: These caregiver experiences indicate that improvements are urgently needed in the recognition of childhood cancer symptoms at primary healthcare level in SA. They also highlight a need for increased financial support from government through social grants, travel allowances and nutritional support.

Evaluation of alignment of the reimbursement medicines list for children in Albania with the WHO essential medicines list for children.

Background: The WHO Essential Medicine List for Children was released on the 30th anniversary of the general Essential Medicine List in 2007, to recognise special needs for medicines in children, and to promote the inclusion of paediatric medicines in national procurement programmes. This study aimed to investigate the alignment of the medicines included in the Albanian reimbursement medicines list of the Mandatory Healthcare Insurance Fund (AMHIF) and the Essential Medicine List for Children. Methods: A quantitative evaluation was performed to compare the paediatric medicines included in the 2022 list of the AMHIF and the 2021 WHO Essential Medicine List for Children. In addition, vaccines in the Albanian vaccination programmes for children were compared to the ones listed on the WHO Essential Medicine List for Children. Results: Both lists had a total of 284 active ingredients in common, whereas 14 of 24 vaccines were found to be in common in the Essential Medicine List for Children list and the Albanian vaccination programmes. Conclusions: This is the first study in Albania to investigate the alignment of the WHO EMLc and AMHIF list. In case of the same active ingredient there were many deviations in terms of dosage form, strength and indication.

Outer packaging labelling of medicines in Southern African Development Community (SADC) countries: comparative analysis of requirements and transition terms for harmonisation.

INTRODUCTION: The COVID-19 pandemic highlighted an urgent need for harmonised requirements for the regulation of medicines. To fully implement harmonised medicines regulations across Africa, common technical standards of medicine regulations are needed. One such technical standard is the labelling of medicines on outer packaging. In this study, we compared outer packaging labelling requirements and transition terms for harmonization for countries in the Southern African Development Community (SADC) region. METHODS: Data on legislation and/or regulatory guidelines for medicine outer packaging labelling from National Medicines Regulatory Authorities (NMRAs) were obtained for countries in the SADC region (n = 16) by February 2023. A detailed comparative content analysis was conducted to determine alignment with the requirements of the Southern African Development Community (SADC) harmonised labelling guidelines to assess readiness levels of each country to transition to the SADC harmonised labelling guideline for outer packaging of medicines. RESULTS: Content analysis showed at least 11 out of 16 countries require national legal reform to transition to the SADC harmonised labelling guideline. In all cases where countries specified labelling requirements for outer packaging of medicines, these were stipulated in national medicines legislation. CONCLUSION: Even though there is a high level of alignment across the countries in terms of national labelling requirements, most countries in the SADC region would still require national legislative reform to transition to regional harmonised labelling requirements and then ultimately to continental requirements of the African Medicines Agency (AMA).

SDG indicator 3.b.3 - an analysis of its robustness and challenges for measuring access to medicines for children.

BACKGROUND: Sustainable Development Goal (SDG) indicator 3.b.3 monitors progress in medicines' accessibility for adults and has significant limitations when applying to medicines for children. An adapted indicator methodology was developed to fill this gap, but no proof of its robustness exists. We provide this evidence through sensitivity analyses. METHODS: Data on availability and prices of child medicines from ten historical datasets were combined to create datasets for analysis: Dataset 1 (medicines selected at random) and Dataset 2 (preference given to available medicines, to better capture affordability of medicines). A base case scenario and univariate sensitivity analyses were performed to test critical components of the methodology, including the new variable of number of units needed for treatment (NUNT), disease burden (DB) weighting, and the National Poverty Line (NPL) limits. Additional analyses were run on a continuously smaller basket of medicines to explore the minimum number of medicines required. Mean facility scores for access were calculated and compared. RESULTS: The mean facility score for Dataset 1 and Dataset 2 within the base case scenario was 35.5% (range 8.0-58.8%) and 76.3% (range 57.2-90.6%). Different NUNT scenarios led to limited variations in mean facility scores of + 0.1% and -0.2%, or differences of + 4.4% and -2.1% at the more critical NPL of $5.50 (Dataset 1). For Dataset 2, variations to the NUNT generated differences of + 0.0% and -0.6%, at an NPL of $5.50 the differences were + 5.0 and -2.0%. Different approaches for weighting for DB induced considerable fluctuations of 9.0% and 11.2% respectively. Stable outcomes with less than 5% change in mean facility score were observed for a medicine basket down to 12 medicines. For smaller baskets, scores increased more rapidly with a widening range. CONCLUSION: This study has confirmed that the proposed adaptations to make SDG indicator 3.b.3 appropriate for children are robust, indicating that they could be an important addition to the official Global Indicator Framework. At least 12 child-appropriate medicines should be surveyed to obtain meaningful outcomes. General concerns that remain about the weighting of medicines for DB and the NPL should be considered at the 2025 planned review of this framework.

Pharmaceutical Scientists' Perspectives on Capacity Building in Pharmaceutical Sciences.

With the anticipated health challenges brought by demographic and technological changes, ensuring capacity in underlying workforce in place is essential for addressing patients' needs. Therefore, a timely identification of important drivers facilitating capacity building is important for strategic decisions and workforce planning. In 2020, internationally renowned pharmaceutical scientists (N = 92), largely from the academia and pharmaceutical industry, with mostly pharmacy and pharmaceutical sciences educational background were approached (through a questionnaire) for their considerations on influencing drivers to facilitate meeting current capacity in pharmaceutical sciences research. From a global view, based on the results of the questionnaire, the top drivers were better alignment with patient needs as well as strengthening education - both through continuous learning and deeper specialisation. The study also showed that capacity building is more than simply increasing the influx of graduates. Pharmaceutical sciences are being influenced by other disciplines, and we can expect more diversity in scientific background and training. Capacity building of pharmaceutical scientists should allow flexibility for rapid change driven by the clinic and need for specialised science and it should be underpinned by lifelong learning.

Non-adherence to guideline recommendations for insulins: a qualitative study amongst primary care practitioners.

BACKGROUND: Guideline adherence is generally high in Dutch general practices. However, the prescription of insulins to type 2 diabetes mellitus patients is often not in line with the guideline, which recommends NPH insulin as first choice and discourages newer insulins. This qualitative study aimed to identify the reasons why primary care healthcare professionals prescribe insulins that are not recommended in guidelines. METHODS: Digital focus groups with primary care practitioners were organised. A topic list was developed, based on reasons for preferred insulins obtained from literature and a priori expert discussions. The discussions were video and audio-recorded, transcribed verbatim and coded with a combination of inductive and deductive codes. Codes were categorized into an existing knowledge, attitudes and behaviour model for guideline non-adherence. RESULTS: Four focus groups with eleven general practitioners, twelve practice nurses, six pharmacists, four diabetes nurses and two nurse practitioners were organised. The prescription of non-recommended insulins was largely driven by argumentation in the domain of attitudes. Lack of agreement with the guideline was the most prominent category. Most of those perspectives did not reflect disagreement with the guideline recommendations in general, but were about advantages of non-recommended insulins, which led, according to the healthcare professionals, to better applicability of those insulins to specific patients. The belief that guideline-recommended insulins were less effective, positive experience with other insulins and marketing from pharmaceutical companies were also identified as attitude-related barriers to prescribe guideline-recommended insulins. One additional category in the domain of attitudes was identified, namely the lack of uniformity in policy between healthcare professionals in the same practice. Only a small number of external barriers were identified, focusing on patient characteristics that prevented the use of recommended insulins, the availability of contradictory guidelines and other, mostly secondary care, healthcare providers initiating non-recommended insulins. No knowledge-related barriers were identified. CONCLUSIONS: The prescription of non-recommended insulins in primary care is mostly driven by lack of agreement with the guideline recommendations and different interpretation of evidence. These insights can be used for the development of interventions to stimulate primary care practitioners to prescribe guideline-recommended insulins.

Unmet Medical Need as a Driver for Pharmaceutical Sciences - A Survey Among Scientists.

Historical antecedents of pharmaceutical sciences are sound on product orientation based on (analytical) chemistry, drug delivery and basic pharmacology. Over the last decades we have seen a transition towards a stronger disease orientation. This raises questions on whether, how and to what extent unmet medical need (UMN) is important in priority setting, funding and impact in pharmaceutical sciences. An online survey in 2020 collected perspectives of internationally recognised pharmaceutical scientists (N = 92), mainly from academia and industry, on drivers and influencing factors in pharmaceutical sciences. The study offers a unique global perspective, demonstrating a solid command of the global needs in pharmaceutical sciences. The survey revealed that UMN is currently seen as one of the three most important drivers, also in addition to emerging trends in science and opportunities driven by collaboration. There are expectations that UMN's impact becomes more influential. This was consistent for both industry and academic respondents. The majority of respondents also indicated that anticipated lessons learned from COVID-19 will strengthen the impact of UMN on science and leadership. This is important as prioritisation of research towards UMN can address the clinical needs where needed the most.

Linking market authorizations of medicines with disease burden in South Africa.

BACKGROUND: Sub-Saharan Africa is going through an epidemiological transition, including an impressive increase in non-communicable diseases. The introduction of medicines has not kept pace with the needs in developing countries. The objectives of this study were to (i) examine the correlation between the number of medicine approvals and disease burden and (ii) compare approval timelines of medicines with disease burden in South Africa in the period 2012-2017. METHODS: The dataset was compiled from publicly available data on medicines registered in South Africa between 2012 and 2017. A correlation analysis was conducted to determine the level of alignment between the number and nature of medicines registered, as determined by the WHO ATC Classification and the Lancet Global Burden of Disease data. Median registration timelines were determined to assess whether medicines for diseases of higher burden were registered faster. RESULTS: A total of 3059 registered medicines were included in the study, including 2779 generic medicines, 267 new chemical entities and 13 vaccines. There was a high level of alignment between the number of medicines registered to treat diseases with higher disease burden levels more effectively, except for lower respiratory tract infections and HIV/AIDS which showed less medicines registered as compared to expectations based on disease burden, respectively. HIV/AIDS showed a lower level of correlation with a much higher disease burden compared to number of medicines registered, but simultaneously also a much shorter median registration timeline (32 months) compared to the other disease areas. CONCLUSIONS: There was generally a high level of alignment between disease burden and number of medicines authorised, except for HIV/AIDS and lower respiratory tract infections. Regulatory authorities should continue to consider burden of disease data to ensure that public health needs are met.

Selection of essential medicines for the prevention and treatment of cardiovascular diseases in low and middle income countries.

BACKGROUND: The incidence and mortality of cardiovascular diseases (CVDs) in low and middle income countries (LMICs) have been increasing, while access to CVDs medicines is suboptimal. We assessed selection of essential medicines for the prevention and treatment of CVDs on national essential medicines lists (NEMLs) of LMICs and potential determinants for selection. METHODS: Only operational NEMLs were considered eligible for this study. A selection of medicines listed under "cardiovascular medicines" or "blood products and plasma substitutes" in the NEMLs were included if they were present on international guidelines for the prevention and treatment of CVDs (hyperlipidemia, hypertension, platelet inhibition, ischemic stroke, stable ischemic heart disease, acute coronary syndromes, heart failure, atrial fibrillation, peripheral arterial disease and acute limb ischemia). The number and diversity of essential medicines selected for CVDs were studied. Moreover, determinants of selection of essential medicines for CVDs at a national level were explored. Data analysis was done using univariate linear regression and non-parametric tests. RESULTS: All medicine groups listed by the international guidelines were selected by the majority of the 34 countries studied with the exception of adenosine diphosphate receptor inhibitors which appeared on less than half of the NEMLs studied (41% of countries). The total number of essential medicines for the prevention and treatment of cardiovascular diseases (median 24 (range 16-50)) differed significantly across income levels (median range: 19.5-25, p = 0.014) and across regions (median range: 20-32, p = 0.049). When recommendations of the international guidelines were considered, over 75% of the NEMLs contained essential medicines for the majority of CVDs. CONCLUSION: The main medicine classes for the management of CVDs were represented on NEMLs. Consequently, for the majority of CVDs, evidence-based guideline-recommended treatment is possible as far as selection of essential medicines is concerned. Selection will therefore not be the limiting step in access to medicines for cardiovascular diseases.

NOACs replace VKA as preferred oral anticoagulant among new patients: a drug utilization study in 560 pharmacies in The Netherlands.

BACKGROUND: In 2012, around 400.000 patients in the Netherlands were treated with Vitamin K Antagonists (VKA) for thromboembolic diseases. Since 2011, non-VKA oral anticoagulants (NOACs) are available. NOACs do not require frequent INR monitoring which benefits patients, but also imposes a risk of reduced therapy adherence. The objective of this study is to describe uptake and patient adherence of NOACs in The Netherlands until October 2016. METHODS: Prescription data for 247.927 patients across 560 pharmacies were used to describe patient profiles, uptake of NOACs among new naive patients and switch between VKA and NOACs, and calculate therapy adherence as the Proportion of Days Covered (PDC). RESULTS: During the studied period the share of NOACs in oral anticoagulants has grown to 57% of prescriptions to new patients. More than 70% of new NOAC users were new naive patients and around 26% switched from VKA. The overall share of NOACs among starters is largest in the group of patients of 50-80 years. Calculated compliance rate for NOAC patients shows that 88% of all users are adherent with a PDC higher than 80%. CONCLUSIONS: NOAC have overtaken VKA as the major treatment prescribed to new oral anticoagulant patients, and the number of starters on VKA is decreasing. Patients are generally adherent to NOACs during the implementation phase, the period that the medication is used. Fear for inadherence by itself does not need to be a reason for not prescribing NOACs instead of VKA.

Variability in market uptake of psychotropic medications in Europe reflects cultural diversity.

BACKGROUND: In the last 20-30 years, many international studies have found substantial differences in the use of (older) psychotropic medication between European countries. The majority mentioned an important role for attitudes and beliefs towards psychotropic medication. So far, no studies have looked into the effects of cultural diversity on the use of new medications entering the market. As national cultures relate deeply to held values regarding, for example, what is seen as effective versus ineffective or safe versus dangerous, (cultural) diversity in decision making around the role of new medications in clinical practice may already be expected from the first day after market authorization. METHODS: This study examined the relation between cultural diversity, described in Hofstede's model of cultural dimensions (Power Distance, Individualism, Masculinity, Uncertainty Avoidance, Indulgence and Long-Term Orientation) and utilization of three new psychotropic medications, namely aripiprazole, duloxetine and pregabalin in Europe. Country level sales data of the case study medications were correlated to country-specific scores of Hofstede's cultural dimensions. IMS Health's MIDAS database has been used for sales data (converted to Defined Daily Doses/1000 inhabitants/day) for the case study medications from the market authorization date in 2004 until December 2009 for 23 EU member states. RESULTS: Consumption of the case study medications was seen in all countries. In general, pregabalin was used more often than aripiprazole and duloxetine. In 2 years after market authorization, approximately 80% of all countries have reported use of all three molecules. Correlations between Hofstede dimensions individualism, long-term orientation and indulgence and total use of the case study medications tended to become stronger over time, but they were only statistically significant for indulgence at two years after market authorization (rho = 0.51, p = 0.014) and three years after market authorization (rho = 0.54, p = 0.008). A more detailed analysis showed (slight) variation by molecule. CONCLUSIONS: This study is a first step in including cultural dimensions when explaining cross-national variation in the use of new medications. The results indicate that indulgence, however marginally, is a cultural aspect that relates to the utilization of new psychotropic medications, suggesting that within the cultural context, less regulation of social norms is a main factor in explaining cross-national variation in uptake of these medications.

Renal function of MDR-TB patients treated with kanamycin regimens or concomitantly with antiretroviral agents.

SETTING: To compare renal insufficiency among multidrug-resistant tuberculosis (MDR-TB) patients treated with kanamycin (KM) based regimens and those treated concomitantly with tenofovir disoproxil fumarate (TDF) or other antiretroviral therapy (ART) regimens in Namibia. DESIGN: Retrospective review of the treatment records and laboratory tests of patients initiated on MDR-TB treatment (January-December 2014). The glomerular filtration rates (eGFR) estimated pre- and post-treatment were compared using the analysis of variance test. Renal insufficiency was defined as an eGFR of <60 ml/min/1.73 m2. Use of KM or TDF and association with renal insufficiency was assessed using Kaplan-Meier plots and Cox proportional hazards analysis. RESULTS: The baseline mean eGFR for the three groups was similar (P = 0.24): 139.3 ± 25.6 ml/min for the KM group (n = 68), 131.1 ± 25.7 ml/min for the KM+TDF group (n = 44) and 134.2±34.4 ml/min for the KM+Other group (n = 23). After 8 months, the values had declined significantly to respectively 104.8 ± 37.5 ml/min (P < 0.001), 101.5 ± 38.3 ml/min (P < 0.001) and 111.5 ± 41.7 ml/min (P = 0.01). Co-treatment with KM+ART was associated with an increased risk of renal insufficiency (hazard ratio [HR] 1.8, 95%CI 0.7-4.1, P = 0.20 for KM+TDF, and HR 3.5, 95%CI 1.4-8.2, P = 0.005 for KM+Other ART). CONCLUSION: Renal function declined at a similar rate in MDR-TB patients treated with KM-based regimens compared with patients treated concomitantly with TDF-based or other ART. The risk of renal insufficiency was greater for patients on ART.

Drug-induced progressive multifocal leukoencephalopathy: Lessons learned from contrasting natalizumab and rituximab.

Progressive multifocal leukoencephalopathy (PML) has been identified as a serious adverse drug reaction (ADR) of several immunomodulatory biologicals. In this study, we contrasted the reporting patterns of PML for two biologicals for which the risk was identified at different points in their lifecycle: natalizumab (before reapproval) and rituximab (nine years postapproval). We found that, apart from the differences in clinical characteristics (age, gender, indication, time to event, fatality), which reflect the diversity in context of use, PML reports for natalizumab were more complete and were received sooner after occurrence. This study serves as an important reminder that spontaneous reports should only be used with great caution to quantify and compare safety profiles across products over time. The observed variability in reporting patterns and heterogeneity of PML cases presents challenges to such comparisons. Lumping uncharacterized PML reports together without taking these differences into account may result in biased comparisons and flawed conclusions about differential safety.

Long term trends in oral antidiabetic drug use among children and adolescents in the Netherlands.

AIM: The aim of the study was to document long term trends in oral antidiabetic drug (OAD) use among children and adolescents in the Netherlands. METHODS: A population-based cohort study was conducted using the Dutch PHARMO Database Network. All patients younger than 20 years old with at least one OAD dispensing were identified. Age-adjusted and age-specific incidence (1999-2011) and prevalence (1998-2011) rates of OAD use were calculated. Trends over time were assessed using joinpoint regression software. A subset of PHARMO Database Network (including community pharmacy dispensing records linked to general practitioner data (OPD-GP database)) was used to assess indications for OADs. RESULTS: In 2011, the overall age-adjusted incidence and prevalence rates of OAD use were 20.7/100 000 (95% CI 19.2, 22.1) person-years (PY) and 53.8/100 000 (95% CI 51.5, 56.1) persons, respectively. The average annual percentage change (AAPC) in the overall age-adjusted incidence rates from 1999 to 2011 was 18.9% (95% CI 4.5, 35.2). The incidence and prevalence rates of OAD use were higher among females and older age categories. The increases in rates of OAD use were mainly driven by metformin. For only 50% of the 98 patients in the OPD-GP database, indications for OAD prescriptions were reported with type 1 diabetes (n = 20), type 2 diabetes (n = 16), and overweight/obesity (n = 10). CONCLUSIONS: Incidence and prevalence rates of OAD use in children and adolescents substantially increased in the Netherlands, especially among older age categories (10-14 and 15-19 years) and females. The main indications for use of OADs were type 1 and 2 diabetes and overweight/obesity.

Risk management plans as a tool for proactive pharmacovigilance: a cohort study of newly approved drugs in Europe.

Risk Management Plans (RMPs) have become a cornerstone in the pharmacovigilance of new drugs in Europe. The RMP was introduced in 2005 to support a proactive approach in gaining knowledge on safety concerns through early planning of pharmacovigilance activities. However, the rate at which uncertainties in the safety profile are resolved through this proactive approach is unknown. We therefore examined the evolution of safety concerns in the RMP after initial approval for a selected cohort of 48 drugs, to provide insight into the knowledge gain over time. We found that 20.7% of the uncertainties existing at approval had been resolved 5 years after approval. Because new uncertainties were included in the RMP at a similar rate, the overall number of uncertainties remained approximately equal. The relatively modest accrual of knowledge, as demonstrated in this study through resolution of uncertainties, suggests that opportunities for optimization exist while ensuring feasible and risk-proportionate pharmacovigilance planning.

Selection of oncology medicines in low- and middle-income countries.

BACKGROUND: High cancer mortality rates in low- and middle-income countries (LMICs) have raised concerns regarding access to oncology medicines. Essential medicines are those which satisfy the primary health care needs and provide a basis for public procurement or reimbursement decisions in LMICs. We explored selection of oncology medicines in LMICs through investigating national essential medicines lists (NEMLs) for cancer treatments. METHODS: Recently updated NEMLs were retrieved for 76 countries. Oncology medicines were classified based on therapeutic categories. Countries were clustered based on geographic regions, income levels and burden of cancer (mortality and morbidity). Indicators of frequency (number of medicines), diversity (number of therapeutic (sub)categories) and more importantly absence were measured and compared across countries using parametric and nonparametric tests. RESULTS: The overall median number of oncology medicines on NEMLs was 16 (interquartile range = 23) chosen predominantly from subcategories of 'antineoplastic agents', with substantial variation across regions and income groups. Five countries did not select any oncology medicine and 68% did not have any 'hormones and related agents' on their NEMLs. Newer technologies like targeted therapies were infrequently incorporated. The cluster of countries suffering most from the burden of cancer selected more essential oncology medicines and diversified further. CONCLUSION: The observed selection of oncology essential medicines can reflect insufficiencies and inequalities in access to cancer treatments at least in the public sector of LMICs. Further resources need to be allocated from governments and international organizations to tackle the problem of access to oncology medicines in these countries.

EU marketing authorization review of orphan and non-orphan drugs does not differ.

Marketing authorization application dossiers of 17 orphan drugs (ODs) and 51 non-ODs evaluated by the European Medicines Agency (EMA) in the period 2009-2010 were compared. We aimed to identify whether any differences existed between ODs and non-ODs in number and type of deficits brought forward during the EMA review, regarding the clinical development plan, clinical outcome and medical need and studied whether these deficits were similarly associated with marketing approval in the EU. In 71% of the ODs dossiers and 65% of the non-ODs dossiers marketing approval was granted. Differences in deficits were found, but similarities in the way ODs and non-ODs were reviewed and marketing approval decisions were taken, underline that regulatory standards are equally high.

Personalised medicine as a challenge for public pricing and reimbursement authorities ­ A survey among 27 European countries on the example of trastuzumab.

OBJECTIVES: To survey possible funding models and pricing practices as well as prices for the treatment package of trastuzumab and its accompanying diagnostic test in European countries, as an example of personalised medicines. METHODS: Qualitative descriptive data on national pharmaceutical pricing and funding policies applied to trastuzumab and its accompanying diagnostic test were obtained from a survey among competent authorities from 27 European countries as of August 2011. Further, price data (for the years 2005-2013) of trastuzumab in the respective European countries were surveyed and analysed. RESULTS: In 2011, testing and treatment mainly took place in hospitals or in specific day-care ambulatory clinics. In the European countries either both trastuzumab and the accompanying diagnostic test were funded from hospital budgets (n = 13) or only medicines were funded from the third party payers such social insurances and the test from hospital budgets (n = 14). Neither combined funding of both medicine and diagnostic test by third party payers was identified in the surveyed countries nor did the respondents from the competent authorities identify any managed entry agreements. National pricing procedures are different for trastuzumab versus its diagnostic test, as most countries apply price control policies for trastuzumab but have free pricing for the diagnostic test. The ex-factory price is, on average, €609 per 150 mg vial with powder in 2013; in nine countries the price of trastuzumab went down from 2005 till 2013. CONCLUSION: The example of trastuzumab and its accompanying diagnostic test highlights some problems of the interface between different funding streams (out-patient and hospital) but also with regard to the interface between the medicine applied in combination with a medical device. The findings suggest a need for further developing and refining policy options to address the identified interface issues.

Differences in external price referencing in Europe: a descriptive overview.

OBJECTIVE: This study aimed to provide an up-to-date description as well as comparative analysis of the national characteristics of pharmaceutical external price referencing (EPR) in Europe. METHODS: Review of the country-specific PPRI (Pharmaceutical Pricing and Reimbursement Information) Pharma Profiles written by representatives of the PPRI Network. The Profiles were analysed according to predefined criteria. RESULTS: Of 28 analysed European countries 24 applied EPR in 2010. The majority of countries have statutory rules to implement EPR. Most countries had less than 10 countries in their reference baskets. Higher income countries tend to include higher income countries in their basket, whereas lower income countries refer to lower income countries. Taking the average price of all countries in the basket as the basis to calculate the national price was the most common strategy (n=8). The methodology of EPR has changed in most European countries over the past 10 years (n=19). CONCLUSIONS: EPR is a widely used pricing policy in Europe and is still actively used as well as adjusted by national authorities. However, we still see room for improvement by implementing more detailed legislations in terms of the revision of prices and by identifying alternative countries in case a product is not on the market. We also see the need for formal information sharing (e.g. congresses dedicated to pricing strategies and systems) with other public pricing authorities to learn about the different EPR methodologies as well as the national experiences. These congresses might also give room to better understand national pricing methods including discussions on possible limitations of these pricing methods.