Improving the managed introduction of new medicines: sharing experiences to aid authorities across Europe

The Managed Introduction of New Medicines, Warsaw, Poland, 11–13 May, 2015

The 3-day course on the managed introduction of new drugs was organized by the Piperska group, together with the Polish Agency for Health Technology Assessment and Tariff System and WHO Europe, to share experiences and case histories among health authority and health insurance company personnel, academics and those from commercial organizations from across Europe on potential ways to optimize the managed entry of new medicines. This starts pre-launch with horizon scanning and budgeting, then peri-launch including critical drug evaluation, and finally post-launch including monitoring prescribing of new medicines against agreed guidance and indicators. There were also discussions on issues regarding managed entry schemes and procurement strategies including biosimilars.

Pharmaceutical expenditure is a concern driven by factors including new high-priced medicines [1–4], resulting in new models, starting pre-launch, through peri-launch to post-launch [1,2]. These three pillars formed the basis of the 3-day course organized by the Piperska group [5], the Agency for Health Technology Assessment and Tariff System [6] and WHO Europe.

Course proceedings (key highlights)

Beata Małecka-Libera, the Secretary of State in the Polish Ministry of Health, discussed the need for data on efficacy and cost–effectiveness and the role of Agency for Health Technology Assessment and Tariff System when assessing the value of new medicines. As a government plenipotentiary for the draft Act on public health, she emphasized that access to new medicines is important, but underlined that there are numerous non-drug interventions carried out by authorities that can improve the health of the population.

Hanne Bak-Pedersen discussed the principles for the appropriate use of medicines and current challenges with over 16,000 medicines in development [7], as well as the importance of making transparent, evidence-informed choices when expanding benefit packages. Access to essential, quality and affordable medicines is central to achieving universal health coverage. Proposals include developing new models [4] and using health technology assessment to support reimbursement negotiations as well as formulating demand-side strategies.

Poland is also developing strategies to enhance the rational use of medicines, which were outlined by the president of the Polish National Health Fund, Tadeusz Jędrzejczyk. The introduction of limit groups and limits that promote cheaper generics helps control expenditures, with pharmacies obligated to inform customers about cheaper generics. Pharmaceutical manufacturers also partly cover over-budget expenditure through pay-back systems. Monitoring prescribing and influencing prescribers reduces inappropriate medicine use and costs, including measures to limit physicians’ from prohibiting the substitution of medicines. Future measures include additional education of physicians and patients about medicines and potential alternatives.

Rickard Malmström discussed the experiences in the Stockholm Region based on the ‘Wise List’, encompassing approximately 200 medicines [8]. High adherence is achieved by involving 20 expert groups, comprehensive communication programs and regular feedback [9]. A step-wise model for new medicines has been in operation since 2006 [10]. Critical drug evaluation reports for new medicines are available up to 6 months before launch, with joint guidelines produced before launch. The comprehensive pre-launch campaign with dabigatran limited bleeding episodes in practice [11], and the agreed guidance limited the prescribing of ipilimumab for malignant melanoma in practice given the potential costs of approximately 40 million SEK (€4.3 million).

Horizon scanning is operated by the four-county collaboration in Sweden, including identification and filtering, prioritization, early assessment, dissemination and monitoring. The annual forecasting report is published in Stockholm every year by March [10]. Roberta Joppi discussed the activities of EuroScan as well as the Italian Horizon Scanning project [12]. The latter has four specific aims: producing periodical lists of emerging medicines for which marketing authorization is expected within 12–36 months, evaluating the clinical impact and cost–effectiveness/budget impact of new medicines, giving well-timed information to authorities and identifying further research fields.

Richard Torbett (European Federation of Pharmaceutical Industries and Association) stressed that investment is needed for new medicines to support aging populations [3,7]. This provides a solid framework for subsequent ‘value’ discussions, entailing a four-stage process including agreeing outcome metrics as well as measuring and making the results transparent, and as a result, aligning ‘traditional’ and ‘Big Data’ approaches to support outcome-focused patient care.

Małgorzata Bała discussed the key aspects regarding critical evaluation of new medicines including: systematic error, systematic disposition of trial designs to produce results consistently better or worse than others, tendency to deviate in one direction from a true value and threats to internal validity of studies. Biases include selection bias, performance bias, detection bias, attrition bias and reporting bias [13].

Anna Zawada discussed critical evaluation of new medicines by the Agency for Health Technology Assessment and Tariff System in Poland. The current threshold for economic effectiveness (incremental cost effectiveness ratio [ICER]) is ≤3× gross domestic product per capita (currently PLN 119,600; €29,200) for all medicines including orphan medicines, helped by narrow indications and risk-sharing schemes. In 2015, there were 20 submissions. Added clinical value was proved in only six cases. In six cases, the budget impact estimation was criticized – in two cases, the estimations were much higher than in the submission and in two cases, the agency’s estimations were lower.

Key reimbursement criteria for new medicines in Slovenia include: public health priority; clinical criteria; economic criteria including an economic analysis (current ICER is 1.5× gross domestic product at €25,000/quality-adjusted life-year) and a budget impact analysis (first 3 years); ethical criteria, for example, orphan diseases; and reference sources. Discounts, rebates, price-volume agreements/pay-back schemes or performance-based agreements are also taken into consideration. The latter is considered only for the most expensive medicines.

Reimbursement criteria for new medicines in Lithuania include: the therapeutic value including the level of innovation 2–5 points (5 for a new active substance where there is no previous treatment) and therapeutic benefit 3–10 points (with 10 points for a new medicine with considerable value, and with 1 point deducted for concerns with efficacy, safety or quality of life); the economic value – based on the pharmacoeconomic value (score 1.5, 3, 4.5) and price (0, 1, 2 or 3, where 3 is the lowest price in Europe, based on 15 countries); and the budget impact. For positive listing, new medicines must have a therapeutic value >9; pharmacoeconomic value >4 and negative (neutral) impact on the National Health Insurance Fund (NHIF) budget. If the therapeutic value is >11, pharmacoeconomic value is >4 and there is positive impact on NHIF budget, the medicine is subsequently placed on a waiting list. In 2014, there were 59 decisions of which 22 were positive, 24 negative and 13 medicines were placed on the waiting list. The waiting list is revised every 6 months, and if the budget permits, medicines from the waiting list are included in the positive list.

The Scottish Medicines Consortium deals with uncertainty by the following: giving pre-submission guidance to manufacturers stressing the need to test uncertainty; validation of assumptions and requests for additional analysis during the New Drugs Committee review; and discussions regarding orphan medicines and other modifiers during Scottish Medicines Consortium discussions. Patient access schemes can enhance the value of new medicines, with these issues encompassed in the Scottish Medicines Consortium’s guidance to manufacturers [14]. Angela Timoney also discussed formularies in Scotland including the Lothian Region to improve medicine use, based on their 2013–2016 Pharmacy Strategy [15] and their Strategic Workplan. NHS Lothian has a strong record of governance in medicines management, including the Lothian Joint Formulary giving first- and second-line choices. Key elements to enhance formulary use include making them easy to follow and clinically attractive, being flexible and responsive with regular updates, and thinking locally while acting nationally.

Germany also formally assesses the level of innovation of new medicines based on a six-point scale and links this to prices [16]. One hundred and thirty-two substances have been assessed (as of early March 2015). Of these, 37 have additional benefit, 26 are with partial additional benefit, 55 are without additional benefit, 6 are exempt and 8 are cancelled/withdrawn. Factors influencing contracted prices include innovation levels and prices after deducting discounts among 15 European countries, purchasing power adjusted. Estimated savings of €630 million were generated from these negotiations between 2012 and 2014.

Björn Wettermark discussed monitoring the utilization and outcome of new medicines and experience of registries [17]. Key elements included relevant and valid data on exposure and outcomes, classification systems, quality indicators (QIs), robust and valid methods. Study designs can be descriptive, analytical or interventional.

Key messages for developing QIs, building on suggestions for new medicines [18], include: using only valid and reliable indicators to assess quality use of medicines; QIs are not a magic bullet, but are important tools; prescribing QIs should be developed using systematic methods; and QIs must take implementation issues into account. Dimensions include the perspective; structure–process–outcome; and drug-, disease- or patient-oriented indicators. Indicators in Germany to improve prescribing include monitoring drug costs among physicians, their share of generic scripts and share of ‘me-to scripts’, especially with high potential savings. QIs include share of prescriptions causing adverse reactions and share of elderly patients receiving potentially inadequate medication, especially as 44% of the elderly are exposed to at least one potential interaction of moderate degree and 14% are exposed to a severe degree of interaction. There is now a 2015 framework for economic prescribing including enalapril, lisinopril and ramipril as 75% of defined daily doses of all renin–angiotensin inhibitors including aliskiren.

Successful multifaceted approaches instigated in Slovenia to reduce antibiotic utilization involved extensive educational programs, QIs and prescribing restrictions [19]. There are also ongoing programs to reduce polypharmacy [16] involving QIs and pharmacotherapy groups. Measures in Poland to reduce antibiotic utilization include making prescriptions valid for 7 days, specifying the antibiotic spectrum and ideally using sensitivity analysis. However, this is not necessary if physicians are cognizant of the likely causes of the infection. This initiative reduced antibiotic prescribing and costs, for example, from 31,549 million packages in 2011 to 23,941 in 2013, and reimbursed costs, from PLN 361,849 million in 2011 to PLN 275,121 million in 2013.

WHO recently updated its Essential Medicines List including oncology medicines [20]. Key issues included defining clinically relevant benefits alongside the high cost of new cancer medicines [1,4,21].

Finally, the goal of the Norwegian Drug procurement cooperation (LIS) is to achieve good prices for pharmaceuticals and reduce costs. In 2015, Orion offered a 69% discount for biosimilar infliximab compared to the originator tender price (REMICADE) and a 72% discount compared to its list price [18]. Concerns with potential side effects are being countered by the Ministry of Health funding NOR-SWITCH to compare originators and biosimilars [22]. Other successes with LIS included procuring paclitaxel at NOK 149 for 50 ml in 2012 versus NOK 13,474 for the originator in 2000.

The course was well received (maximum score of 5) with speakers being knowledgeable in their area and clarifying the content (4.8–4.9), the content being appropriate for the audience with appropriate teaching methods (4.5–4.8), which could be applied in practice to achieve personal aims (4.6), and could enhance people’s expertise somewhat (44%) and substantially (56%). Everyone recommended the course to others.

Financial disclosures & competing interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.