Table 4.

Key considerations among stakeholder groups to optimize the managed entry of new drugs (Garattini et al., 2008; Godman et al., 2008, 2009c, 2012a,b,d; Wettermark et al., 2008, 2010a,c; Coma et al., 2009; Adamski et al., 2010; Sermet et al., 2010; Gustafsson et al., 2011; Kolasa et al., 2011; Vončina et al., 2011; Cheema et al., 2012; Siviero et al., 2012; Godman and Gustafsson, 2013).

Stakeholder	Key considerations among stakeholder groups to optimize the managed entry of new drugs
Health authorities/health insurance companies/physician associations	Pre-launch
	• Plan early for the launch of new drugs especially those that could have an appreciable budget impact and/or safety considerations. This can be through working with countries/regions already engaged in such activities • Work alongside key multi-professional groups including independent pharmacotherapeutic experts such as general practitioners, pharmacists, and clinical pharmacology groups. This will help with critically appraising the potential role and value of new treatments ahead of their launch, as well as with developing robust budget impact models for future forecasts. Where possible, Drug and Therapeutic Committees (DTCs) and expert groups should have a major role to ensure consistent priorities for recommendations across divergent pharmacotherapeutic groups •Work with regulators to: °Review potential areas of concern with new treatments, especially around safety issues and potential ways to address this ° Check information provided by commercial organizations is comprehensive, addressing any potential publication bias (Melander et al., 2003; Kirsch et al., 2008; Martin, 2012). The need for this should reduce with ongoing activities among pharmaceutical companies to fully disclose trial data (Kmietowicz, 2013) •Plan early for the: ° Incorporation of any pharmacogenetic tests that should to be available when a new “valued” drug is launched to enhance its appropriate use ° Development of any patient registries to assess the effectiveness/safety of new drugs in practice (pharmacovigilance) as well as monitor prescribing against agreed guidance (Table 3) ° Any necessary re-designing of services, e.g., anticoagulation services with the launch of new anticoagulants • Regularly assess which products will lose their patent in the coming 1–2 years to help fund new premium priced drugs in the disease area/related disease area – especially with growing resource pressures. These activities will assist financial planning generally • Work with pertinent patient groups especially regarding new treatments that could have serious patient issues to help instigate appropriate educational campaigns for physicians and patients pre- to post-launch. Similarly also with key physicians, including those within DTCs, to develop suitable educational and communication materials including guidelines for physicians
	Peri-launch
	• Consider the development of any potential new quality or prescribing indicators together with key stakeholder groups within and across European countries. This includes their assessment in practice, acknowledging that any indicators developed must have content validity, face validity, concurrent validity, construct validity and predictive validity • Include any indicators developed in new guidance/guidelines and, if appropriate, within ongoing financial incentive schemes for physicians to optimize the use of new premium priced drugs at launch • Be critical of any proposed risk sharing arrangements using the criteria summarized in Table 2 – mindful that such arrangements post-launch could facilitate reimbursement and funding of new premium priced drugs (Table A1 in the Appendix – e.g., Netherlands and Slovenia) • Continually check likely launch dates for new treatments with pertinent pharmaceutical companies to improve financial planning
	Post-launch
	• Use administrative and/or medical databases to compare “real world” patients with those included in Phase III RCTs in terms of their clinical features, treatments, and potential outcomes to further refine prescribing guidance and/or reimbursed prices especially if greater co-morbidity in “real world” patients (Joppi et al., 2013) • Build in regular reviews of any reimbursement/funding/guidance especially as more data becomes available, e.g., more recent data challenging “no patient monitoring” with dabigatran especially if “no patient monitoring” was built into submitted economic analyses • Monitor physician adherence to any agreed guidance/reimbursement restrictions and potentially instigate academic detailing and other activities where continued concerns with prescribing
Physicians	Peri-launch
	• Work with health authorities and health insurance companies pre-launch to critically review new treatments, especially where there are concerns with patient safety, to help enhance their appropriate use at launch and their retention on the market • Provide guidance to health authorities and health insurance companies regarding optimal patient populations that maximize the value of new drugs, as well as potential quality/prescribing indicators • Provide input into discussions on the potential value of pertinent pharmacogenetic tests that may help optimize the use of new drugs post-launch • Help with the development of educational materials for physicians and patients peri- and post-launch including the development of any clinical guidelines based on agreed guidance • Assist with the design of any patient registries prior to launch, and follow this up after launch (Table 3). This can also include programs that measure drug sequencing against any agreed guidance • Help authorities critically assess proposed risk sharing arrangements, especially regarding the administrative burden and other key issues (Table 2) • Assist hospital and ambulatory care DTCs with critically evaluating new treatments, as well as with the planning of any interface arrangements to improve the co-ordination of care between primary and secondary care physicians post launch
	Post-launch
	• Provide input into any patient registries (Table 3) to help assess the true value of the new drug especially where there are concerns with safety in a wider co-morbid population post launch than those enrolled into Phase II and III trials • Provide input when clinical guidelines are revised as more data becomes available
Patient organizations	Pre-launch
	• Provide input to health authorities and health insurance companies pre-launch regarding any safety and effectiveness issues for new drugs from the patients’ perspectives • This includes any pertinent pharmacogenetic tests that help optimize the use of new drugs to patient populations where the benefit:risk ratio (and hence “value”) is maximized
	Pre- and peri-launch
	• Provide input into the design and distribution of any patient information regarding new drugs, especially where potential safety issues, pre- and peri-launch • Provide input into the design of any quality/prescribing indicators for new drugs especially where there are issues of safety and sequencing as well as where compliance is likely to be a concern
	Post-launch
	• Help further refine information for patients as more knowledge becomes available about the new drug, especially regarding key side-effects and their implications • Help disseminate factual information to patients if pertinent, especially where there are exaggerated claims unduly raising expectations among patients or where issues of side-effects have not been adequately disseminated
Commercial organizations	Pre-launch
	• Interact early with pertinent health authorities and health insurance companies, especially for new premium priced drugs, to review key comparator and outcome data to include in Phase II/III clinical trials. Comparator and outcome data will depend on the disease area and target prices. Included in this should be discussions regarding resource issues and budget impact at launch to aid planning, acknowledging the particular characteristics of each market • This may include discussions on study design with increasing knowledge of pharmacogenomics and the implications for subsequent trial designs with potentially smaller populations (this will be explored further in future papers) • Provide health authorities and health insurance companies with all relevant data in a timely fashion pre-launch, rather than selective data, to aid decision making and reduce scepticism. This is important to address current concerns that manufacturers are still hiding/not providing data that potentially reduces the value of their product (Martin, 2012); although some companies are now addressing this (Kmietowicz, 2013) • Relevant data includes key adverse event data or pharmacokinetic data - especially if there are concerns about potential claims in practice as seen with concerns with the “no requirement for patient monitoring” with dabigatran • Be pragmatic when planning target prices taking into account key decision making criteria for the pertinent country or region, including either cost/QALY considerations or clinical data requirements for new drugs to be seen as innovative or adding clinical value. This includes any discounts or rebates as part of any risk sharing arrangements (Table 2), acknowledging that the majority of new drugs are seen as similar by payers, with only a minority seen after critical evaluation to have added patient benefits compared with existing standards. These considerations have grown in importance with ongoing resource pressures, i.e., mindful of opportunity cost considerations within health authorities and health insurance companies
	Peri- and post-launch
	• Resist the urge to over promote new drugs especially to the public where there are safety issues, thereby reducing the potential for further restrictions/early withdrawal • Potentially monitor and refine risk sharing arrangements as more data becomes available