payers may often desire head - to - head comparisons and distrust of pharmaceutical sponsored 
 registries , observational cohort studies , or modeling to generate relevant real - world 
 evidence for decision making ( 1719 ) . furthermore , the relative value and weight of 
 different evidence used by payers in decision making varies and is not always transparent . costs and evidence certainty can be  more likely than efficacy and safety data to influence 
 level of formulary access  ( 19 ) . manufacturers 
 must struggle with the inconsistent demands from different payers , as well as the widening 
 disconnect between regulatory and payer evidentiary requirements . evidence requirements of european regulators are often inconsistent with those of payers 
 and health technology assessment ( hta ) bodies . the european medicines agency ( ema ) may 
 accept placebo - controlled or non - inferiority trials to demonstrate the quality , safety and 
 clinical efficacy of their new medicines for marketing authorization applications ( 8;9 ) . payers , on the other hand , generally demand evidence that the medicine under evaluation is 
 more effective than alternative treatment options . regulatory agencies and payers can also 
 express differences in opinion about endpoints , with the former accepting surrogate 
 endpoints as valid markers and the latter preferring clinical outcomes and accepting 
 surrogate outcomes only if clinically relevant and/or validated ( 10;11;20 ) . evidence suggests that many hta bodies and payers in europe 
 prefer head - to - head randomized trials ( 20;21 ) . however , it also recognized that there is a place 
 for other , non - rct data sources ( 12 ) . in a recent survey regarding pragmatic clinical trials ( pcts ) , u.s . payers demonstrated 
 limited use and varying knowledge of pcts ; however , they were interested in the real - world 
 evidence benefits and anticipated increased acceptance of pcts in future ( 22 ) . given payer preferences to see trial data 
 validated in their broader , real - world patient populations , pcts ( which can be thought of as 
  real - world rcts ) may be appropriate to address questions relevant to payers while still 
 retaining high internal validity . the evolution of accountable care organizations ( acos ) may also have major implications for 
 cer evidence demands , with a variety of new care delivery models appearing that align 
 payments with benefits and introduce measures focused on quality of care and the reduction 
 of overall costs . many anticipate that payers will want to see evidence of economic value in 
 addition to clinical value , as compared to existing alternatives ( 13;23 ) . although costs are 
 excluded from the patient protection and affordable care act of 2010 , the establishment of 
 the center for medicare and medicaid innovation placed a clear focus on improving quality 
 and lowering costs by evaluating innovative payment and care delivery models . despite existing payer studies and advances in cer / re methods , the extent to which payers 
 anticipate how they will use cer / re for future access decisions remains unclear . our study 
 attempts to address this unknown by grounding our discussion in hypothetical cases and 
 examines specific methodologies often associated with cer / re ( e.g. , indirect comparisons , 
 cluster rcts ) to obtain perspectives about their usefulness . importantly , however , we look 
 to the near - future , anticipating how the environments in the united states and europe are 
 likely to change between now and 2020 , how changes will influence payer information needs , 
 and how cer / re evidence may be accepted to fulfill those information needs . key informants were identified from existing professional contacts and online 
 executive / organizational leadership rosters and recruited by means of email to participate 
 in the project . we sought senior officials representing large payers , pharmacy benefits 
 managers ( pbms ) , hta groups , and pricing and reimbursement bodies in the united states ( as 
 this represents a sizeable portion of current pharmaceutical company revenue ) and europe 
 ( in recognition of the global environment in which companies operate ) , who played a role 
 in coverage and/or pricing decisions or policies in their organizations . our initial set 
 of european countries included the five major markets ( france , italy , germany , spain , and 
 the united kingdom ) and two additional countries ( the netherlands and sweden ) where we 
 found evidence of systematic re - evaluations based on additional data collected while a 
 drug is used in practice ( 21 ) . in the united 
 kingdom , two hta bodies ( the national institute for health and care excellence and the 
 scottish medicines consortium ) operating in different jurisdictions were considered in the 
 study as both consider cost effectiveness data in their decision making . key informants for integrated health systems and acos . to guide the development of our survey and interview plan , we reviewed key literature in 
 cer / re methods ( table 1 ) . using the qualtrix 
 online survey platform , we developed a brief survey instrument for our interviewees to 
 complete before their interviews , assessing current use of cer / re evidence and potential 
 trends that might influence its use for decision making by 2020 . a glossary of key terms 
 accompanied the survey as a resource for key informants . we developed a semi - structured 
 interview guide that could be tailored to individuals ' survey responses . for both the 
 united states and europe , interviews were conducted by a pair of researchers ( one 
 interviewer and one note taker ) . table 1.literature reviewdescriptionwe conducted a non - systematic literature review by 
 searching medline ( pubmed ) and the grey literature ( pcori , iom , ahrq , pcast ) 
 for key papers in cer / re methods , focusing on innovative or less common study 
 designs , statistical methods and data sources . payer perspectives on cer evidence for decision making and 
 current re requirements from european hta and pricing bodies . we searched key 
 words associated with specific methods or designs ( e.g.  cluster randomized 
 trials ,   indirect comparisons  ) individually and in combination with key 
 words such as  payers ,   coverage decisions , ,  drugs ,   formulary ,  in 
 addition to broader searches for  comparative effectiveness research methods  
 ( or cer methods or relative effectiveness methods ) and  payers  or  pricing we searched google scholar to identify publications in the peer reviewed 
 and grey literature providing evidence of hta or pricing and reimbursement 
 requirements in 8 selected jurisdictions ( england and wales , france , germany , 
 italy , the netherlands , scotland , spain , and sweden ) . stakeholders on 
 choosing the appropriate study designs for specific cer questions , and a 
 review of hta requirements across several european systems . the survey was piloted for duration , ease of use , interpretability and appropriateness of 
 questions , among three professional contacts in the united states and canada and two in 
 europe who are experts in hta , cer / re and coverage decision making . pilot participants 
 then completed 60- to 90-minute cognitive interviews to share personal interpretations of 
 the survey and semi - structured interview questions and help identify contextual elements 
 of the hypothetical references cases ( table 2 ) 
 that might create conflict or challenges for payers . cases were revised and became the 
 center of the semi - structured interview based on this feedback . survey items were also 
 modified , separated out by study designs , methods and sources of information in a series 
 of matched  current  and  future  questions . table 2.description of hypothetical reference caseshypothetical reference casescase 1a new drug that is a breakthrough for treating 
 patients with a common chronic disease but has been studied only in a small 
 population that has a specific biomarker identified by a companion diagnostic 
 test.case 2a new drug that demonstrates no or marginal 
 difference in efficacy between alternative drugs in phase iii trials . however , 
 the new drug uses a more convenient route of administration than existing 
 competitors because it does not require visits to the doctor 's office . this 
 raises the possibility that patients will adhere to the new drug more than the 
 competitors.case 3a new drug in a crowded , competitive market for a 
 common chronic disease with a demonstrated efficacy similar to its 
 competitors . the manufacturer has identified several potential subgroups where 
 the drug may be more effective ; however , those subgroup analyses were 
 underpowered and not planned a priori . of the subgroups examined post hoc , one 
 group was patients who did not improve on their initial therapies.case 4a new drug for a disease where no alternative 
 pharmaceutical treatment exists . there is a surgical procedure considered a 
 treatment , that requires general anesthesia , and which is performed only with 
 poor to moderate success . description of hypothetical reference cases survey responses were tabulated , however individual - level changes in paired  current  and 
  future  questions were documented and incorporated into the semi - structured key informant 
 interviews . we conducted a systematic content review , similar to a directed content 
 analysis ( 24 ) . instead of in - depth coding of 
 interviews , we sought to extract explicit content in response to the questions raised 
 during the key informant interviews . a single reviewer extracted relevant information 
 specific to an existing framework which followed the construct of the semi - structured 
 interview guide . fourteen key informants from five countries participated ( table 3 ) ; of these , two completed only the interview , although their 
 perspectives on the survey questions were gathered in the interview itself . table 3.characteristics of payer key informants , united states and europeunited statesus1public payercms officialinvolved in medicare coverage determinationsus2public payerstate medicaid medical directorworks with pharmacy benefits manager but leads overall 
 coverage determination processus3large private payervp , hospitals , quality & care deliveryleads national quality and care delivery agenda , 
 co - chairs the medicare part d formularyus4large private payerdirector , health technology assessmentmakes recommendations to voters on what should be 
 considered medically necessaryus5large pharmacy benefits managerchief medical officerleads healthcare strategy , clinical & medical 
 affairsus6large private payer + accountable care organizationmedical policy , technology assessment , and 
 credentialingleads pharmacy & therapeutics process and 
 medical policy processus7large private payer + accountable care organizationclinical policy research and development , pharmacy and 
 therapeuticsoversees clinical policies and co - chairs pharmacy 
 & therapeutics committeeus8integrated health systemchief medical officerleads strategic direction of performance improvement 
 in quality and patient safetyeurope : united kingdom ( including 
 scotland and england and wales ) , spain and swedenidpayer perspectivedescription of organization or roleeu1hta bodyformer member of appraisal committee , 
 expert in health sciences methodologyeu2hta bodyleadership role , research and 
 developmenteu3regional pricing and reimbursementleadership role , pharmacyeu4government agency , pricing & reimbursementexpert in health economicseu5government agency , pricing & reimbursementstudy coordinatoreu6hta bodyappraisal committee member characteristics of payer key informants , united states and europe overall , rcts were payers ' preferred source of cer / re evidence , both generally and in 
 response to the hypothetical reference cases . when asked to define cer in their own words , 
 u.s . informants emphasized randomization and the use of appropriate comparators as essential 
 aspects of cer . efficacy rcts were considered a potential type of cer study , depending on 
 their usefulness , such as active - comparator trials with head - to - head comparisons of relevant 
 clinical alternatives , or placebo - controlled trials that could be combined with other data , 
 for example , in indirect comparisons . in general , a broad range of observational and 
 experimental study types fit under  cer . no one found cer and pcor to conflict , but 
 suggested cer could be conducted without being patient - centered ( e.g. , comparing the 
 effectiveness of treatment alternatives for glycemic control may be important to physicians 
 and payers , whereas diabetes patients may be more concerned with quality of life , vascular 
 conditions , or mortality ) . when asked to define re in their own words , european key 
 informants described similar meanings : in general , how a technology performs in practice 
 compared to an appropriate comparator . part of an hta . in the survey , payers favored direct head - to - head comparisons as  extremely relevant  to 
 their decision making ( supplementary table 1 ) . the inclusion of meaningful endpoints and 
 study populations representative of  real world  patients were  very  or  extremely informants , and all european informants indicated that a study population 
 being representative of real - world patients was  very  or table 4 summarizes high - level take - away points from 
 the key informant interviews in response to the open - ended questions regarding study 
 designs , methods and data sources which preceded the hypothetical reference cases . by 2020 , rcts will still be preferred for initial market access in the united states and europe , 
 despite improvements in observational research methods and a growing data - rich environment . 
 there may be a larger role for observational study designs following 
 initial approval , to support decisions about formulary placement and premium pricing in 
 competitive markets . european informants also anticipated the continuing growth of adaptive 
 trials and use of study data from registries , and considered patient reported outcomes 
 ( pros ) to be only one component of re . table 4.high level findings from non  case - specific interview questionsdomain : study designsu.s . respondents(n = 

 8 
 ) - observational evidence may inform future clinical 
 practice guidelines in u.s . by leveraging enriched databases and advanced 
 statistics to identify observable characteristics that inform personalized 
 medicine- more adaptive trials expected in 2020- u.s . payers 
 more familiar with delayed designs- integrated health records and 
 uniformity among plans will enable the conduct of these studies by payerseuropean respondents ( n = 

 6 
 ) - more use of national registry data in europe in the 
 future- more adaptive trials expected in 2020 , though infrastructure 
 issues in some countries may limit their potentialall ( n = 

 14 
 ) - rcts will remain preferred study design- 
 cluster rcts being used by some ( u.s . and eu ) but not familiar to all- 
 other potential uses of observational evidence:- long term safety , cost , 
 & effectiveness of multiple new drugs in a class compared to existing 
 standard of care- identifying meaningful subgroups for which differences 
 in treatment effect might later be confirmed by an rctdomain : methods / analyticsu.s . respondents- large modeling groups such as archimedes , inc , and 
 gns healthcare , may drive the sophistication and application of advanced 
 statistics to  big data ,  hypothesis - free association studies , and 
 trial simulations- by 2020 u.s . key population based decision makers may 
 use cost utility analyses more ofteneuropean respondents- methods of adjusting for bias in re might increase 
 in usability with gradual acceptance of methodological standards , but current 
 techniques still need to be improved- complexities in explaining these 
 methods to high level decision makers also a concernall- bayesian statistics and advanced modeling expected 
 to increase by 2020- indirect comparisons have  methodologically come of 
 age  in both europe and the u.s- still need to improve matching 
 methodology to account for comparisons of different study populations- 
 may get used less if the relevance and efficiency of clinical 
 trials improve.domain : data capacity & burden 
 of evidence generationu.s . payers and healthcare systems , between payers and independent research groups , 
 large practice consolidations , and integration of data within single large payer 
 systems will likely generate large amounts of clinically enriched 
 individual - level observational datasets.- costs of database maintenance , 
 proprietary , legal and oversight issues are potential barriers to sustainable 
 data sharing infrastructures for cer- fda mini - sentinel a potential 
 facilitator.- potential for misuse , such as data - mining and 
 underreporting of negative results were concerns- role of manufacturers 
 may evolve into helping develop standards and common language as other 
 stakeholders play a greater role in cer evidence generationeuropean respondents- increased use of national registries anticipated in 
 europe- potential shift to greater use of electronic health records data 
 in europe , extent to which is unclear- major concerns : information 
 technology capability issues , provision and storage of information , and some 
 dependencedomain : accountable careu.s . aco or integrated care respondents 
 ( n= 
 3 
 ) - more use of risk - adjusted per member per month 
 payments anticipated in the future , leading to more integrated understanding of 
 drug utilization and resource use- anticipated shift in performance 
 metrics toward more sophisticated measures encompassing cost and measures of 
 adherence and leading to more judicious decisions about use of medical 
 care- clinical autonomy a potential limiting factor : physicians will 
 continue to take individual patient preferences seriously- ability to 
 evaluate drug effectiveness within acos will likely depend on ability to remain 
 partnered with pbms , who typically house the drug claims data- acos may 
 have own care pathways for which uncovered products might be absorbed if overall 
 cost saving is achieved- smaller acos may remain focused on improving 
 their data and developing appropriate quality measuresfor purposes of the project , we defined  big data  as a repository of a 
 voluminous amount of unstructured or semi - structured data on diverse care settings 
 that can be speedily accessed and the use of predictive analytics and data mining to 
 undercover hidden patterns and unknown correlations . high level findings from non  case - specific interview questions for purposes of the project , we defined  big data  as a repository of a 
 voluminous amount of unstructured or semi - structured data on diverse care settings 
 that can be speedily accessed and the use of predictive analytics and data mining to 
 undercover hidden patterns and unknown correlations . key informants expected drugs resembling case 1 ( table 2 ) to be more common by 2020 . for this case , they most often 
 asked for an rct or pct in a broader population comparing outcomes of patients without a 
 biomarker to other alternatives . indirect comparisons , retrospective analyses of payer data , 
 registries , or rigorous prospective observational studies were also discussed . among u.s . key informants , the majority expressed concern about the potential for indication creep ( or 
 diffusion of the use of the new drug into broader , off - label populations ) and would attempt 
 to use available policy tools to control uptake and diffusion . european key informants 
 focused on appropriate outcomes , that is , the acceptance of surrogate outcomes may depend on 
 the drug 's place in therapy . consensus was that manufacturers should be responsible for 
 generating post - launch re evidence in europe , although there was recognition that in some 
 cases there are insufficient incentives to do so . key informants would expect strong evidence to come from 
 manufacturers , three would analyze their own data , and one would consider a partnership akin 
 to coverage with evidence development . regarding case 2 ( table 2 ) , 
 public and private u.s . 357 , 2002 and 
 section 1862(a)(1)(a ) of the social security act 
 ( the act ) , 42 u.s.c . 1395y(a ) : the secretary may only pay for items and services that are 
  reasonable and necessary for the diagnosis or treatment of illness or injury or to improve 
 the functioning of a malformed body member . ) conventional , less costly alternatives would 
 likely be preferred , without robust evidence that linked the new drug to improved clinical 
 outcomes or ( in some cases ) adherence as a surrogate . three u.s . and two european informants might accept registry data or other 
 prospective observational studies instead of randomized trials in therapeutic areas where 
 adherence was more clinically important for disease management , where disadvantages of 
 existing alternatives ( such as tolerability or patient burden ) were well documented , or 
 where the price differential between new and existing drugs was not as large . however , a key 
 concern was that important differences would exist between the patients on different 
 alternatives at the time of product launch , restricting the ability to compare in 
 observational data , because the data may reside with different entities . european key 
 informants may also ask for cost effectiveness analyses , stated preference studies , and rcts 
 that sought to capture adherence . key informants were familiar with products resembling case 3 ( table 2 ) and typically stated that underpowered 
 post hoc subgroup analyses were not convincing . key informants would prefer rct 
 data with prospectively identified subgroups that were sufficiently powered to consider 
 premium pricing . however , several key informants expressed a willingness to consider 
 peer - reviewed , prospective observational cohort studies , under certain circumstances . other 
 key informants expressed concerns about manufacturers providing the evidence , publication 
 bias and underpowered subgroup analyses . case 4 ( table 2 ) was considered 
 rare , and perspectives varied , due in part to the ethical and design challenges raised by a 
 standard of care ( surgery ) of questionable effectiveness . key informants  ideally  wanted to see a head - to - head trial , most informants recognized 
 that the availability of evidence on the surgical procedure would influence their demands 
 for randomization , and that an effectiveness study of the surgery might be needed first 
 ( which could be publicly funded in europe ) . informant suggested modeling or 
 meta - analyses , and one european informant suggested identifying patient subgroups where the 
 new treatment would be more appropriate than a surgical procedure . informants , 
 european informants expect to use more national registry data , more data collected 
 post - launch / hta decision ( to reduce uncertainty of pre - launch findings ) and potentially from 
 other jurisdictions . several barriers may influence the availability of re evidence , 
 including : lack of funding for re from healthcare providers , lack of incentives for industry 
 to collect re evidence ( in many countries the access decision is made at launch ) , and 
 comparators being inappropriate and different across countries . case 1 
 ( companion diagnostic ) and case 3 ( post hoc subgroup 
 analysis ) sparked several observations about the future of personalized medicine . payers in particular anticipate a broader 
 picture of personalized medicine enabled by the availability of clinically rich individual 
 level payer data , analyzed in prospective real - world studies to identify observable factors 
 that can guide decision making . we heard from payers that rcts will still be expected for establishing causality and 
 providing evidence of therapeutic effect for initial market access in both 
 the united states and europe , even with improved standards and data quality . payer 
 preferences for appropriate comparators and information on real - world patients support 
 greater use of pragmatic trials before market release in future drug development . however , 
 whether or not pcts can become an efficient design by leveraging existing data is somewhat 
 uncertain . many u.s . payers anticipate a significant growth in the availability of 
 electronic data for cer evidence generation , with implications for multi - stakeholder sharing 
 of the burden of cer / re evidence development . however , european payers expressed concerns 
 that poor health system infrastructure may be a barrier to electronic health records 
 reaching their full potential . on the other hand , investments by payers , health care systems 
 and countries in electronic health data and registries may facilitate delayed design studies 
 and retrospective claims analyses to examine use in covered populations and refine 
 formularies ( for example , delayed design studies might resemble randomized or staggered 
 implementation of policies within a covered population to compare drug usage and health 
 outcomes ) . we might also anticipate a growing role of observational study designs following 
 initial approval to support decisions about formulary placement and premium pricing in 
 competitive markets . as evidenced by reactions to the hypothetical reference cases , although 
 payers / hta bodies may remain circumspect about observational studies or data mining 
 conducted by the pharmaceutical industry , such studies may be acceptable for certain 
 products , under certain contexts . like wang et al . payers express comfort with their own claims data , 
 which are increasingly being enriched with clinical and laboratory data to provide good 
 quality data for observational research . the use of novel designs may also reduce concerns 
 about bias in peer - reviewed observational studies on newly marketed drugs ( 5 ) . for example , inception cohorts or new user designs 
 may help avoid biased comparisons of new users versus prevalent users of a drug , who may 
 differ in several important ways ( 25 ) . manufacturers may benefit from investing in infrastructure for post - market follow - up that 
 anticipates greater competition over time . payers 
 involved in formulary decision making preferred long term cost and outcome data and 
 acknowledged the appropriateness of well - designed observational studies to complement rct 
 findings in broader populations ( 3 ) . these same 
 payers also recommended that manufacturers validate trial findings in real world studies to 
 show payers that outcomes in their plans ' membership reflect rct findings ( 3 ) . epstein suggests more collaboration in analyzing 
 findings , and shared access to raw data including those from clinical studies ( 4 ) . ( 5 ) suggest a multifaceted approach given the lack of early 
 observational data and limitations of electronic health records ( ehrs ) , registries , and 
 claims data . they propose sequential cohort designs , the extension of phase iii and iv 
 trials ( i.e. , patients are followed for longer , perhaps using an observational design ) , 
 indirect comparisons of efficacy , and the use of modeling and trial simulation . like several 
 of our key informants , they see an accelerated trend toward third - party generation of cer / re 
 evidence that leverages longitudinal claims and ehr data from payers and healthcare systems . in a future healthcare environment most conducive to cer / re , where pct enrollment is 
 facilitated by ehr enriched environments , access to patient registries and manufacturer 
 partnerships with advocacy groups or healthcare systems , the drug development paradigm might 
 rely heavily on pcts with extended observational follow - up , including sequential cohort 
 studies and registries . however , a less integrated scenario where electronic data offer some 
 but not comprehensive benefits , may be more likely . still , new platforms for research offer 
 partnership opportunities for manufacturers seeking more efficient ways to conduct rcts . health systems investments and population - based registries offer a basis for efficiently 
 identifying trial populations and collecting clinical trial data using routine data sources . the implications for evidence collection during drug development may depend heavily on 
 whether a product is being marketed broadly in a crowded market but seeking special status , 
 versus being marketed to a targeted population , but with the potential to benefit other 
 groups who are not on label . a major challenge for companies in the competitive  me too scenario ( case 

 4 
 ) is the market competition that can not be predicted at start of a product portfolio : 
 companies often end up in a crowded market , but not by design . improving the efficiency of 
 evidence generation while maintaining validity is key , but a product portfolio may need to 
 allow a certain amount of flexibility to adapt to emerging competitors ( e.g. , add study arms 
 or other outcomes ) , whereas historically many manufacturers might have scrambled toward the 
 end of a product 's evidence development to deal with this competition . companies may also 
 want to consider the future of exploratory research and how the decision point regarding a 
 product 's continuance or discontinuance within a company 's development portfolio might 
 shift . the capabilities of european countries and the united states currently differ ; how each 
 healthcare environment evolves between now and 2020 has implications for healthcare systems 
 capabilities and data availability , which may in turn influence the ability to generate 
 cer / re evidence in different regions . for example , europeans healthcare systems have 
 longitudinal data on patients over the course of care , whereas the u.s . healthcare system is 
 disconnected , but a wealth of electronic data from ehrs and other databases exist . this may 
 explain the greater emphasis on registries among our european informants in contrast to the 
 demand for randomized studies from our u.s . surprisingly , there was little mention by key informants about an increased role of 
 coverage with evidence development , except in the pilot discussions . payers we interviewed that they will increasingly attempt to 
 restrict access through prior authorization , step - therapy , or other policy levers . as data 
 accumulate or classes become crowded , they will re - evaluate outcomes in their own data , a 
 re - iterative process aimed at refining formularies . some european informants thought the 
 evidence received at launch would depend on whether the ema changes its approval process . the studies payers accept may depend on additional evidence the ema is seeking post - launch 
 as part of an adaptive licensing process . should a product get early marketing 
 authorization , there may be a political pressure to provide the product within that 
 country 's health system ; this may require greater use of post - launch studies , perhaps linked 
 to some form of conditional reimbursement . perhaps the inclusion of more advisors to decision makers rather 
 than officials representing the selected decision - making bodies could have increased the 
 response rate . in addition , some european countries included in the final sample are 
 over - represented ( two experts from sweden and three from the united kingdom , although in 
 the latter informants were from different jurisdictions ) . those countries rely primarily 
 on cost effectiveness assessments to make coverage decisions which is not the case in 
 other countries ( i.e. , germany and italy , which not included in the study due to 
 non - response ) . further studies including broader spectrum of european countries might 
 provide additional insights on the future use of re . our study offers insights into the evidence demands manufacturers might anticipate for 
 market access in future healthcare environments . in the most likely future environment , 
 manufacturers will still need to go distinctly for regulatory approval . however , more 
 pragmatic phase iii trial designs may be increasingly feasible and affordable . next steps 
 could involve engaging payers , manufacturers and regulatory agencies in discussions 
 regarding key methodological tradeoffs . from a manufacturer perspective , greater emphasis on 
 post launch investments may first require more clarity on what returns on investment they 
 can expect . payers may contribute by communicating back to manufacturers clear ways in which 
 evidence will have implications for decisions . the authors would like to acknowledge funding support for this project from the following 
 sponsors : amgen , eli lilly & company , glaxosmithkline , novartis , and sanofi - aventis . the authors have no other 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 apart from those disclosed .
objectives : our objective was to gather perspectives from payers on how 
 comparative effectiveness research ( cer ) in the united states and relative effectiveness 
 ( re ) research in europe will impact evidentiary standards for access decisions of new 
 drugs by 2020.methods : we conducted semi - structured interviews with fourteen senior 
 officials representing public and private payers , health technology assessment groups , and 
 pricing and reimbursement bodies in the united states and europe . an online survey 
 assessed current use of cer / re evidence and potential trends that might influence its use 
 for decision making by 2020 . 
 a semi - structured interview elicited payers ' definitions of 
 cer / re and was structured around four hypothetical cases resembling drugs expected to be 
 more common or poised to create policy challenges by 2020 . 
 topics included acceptance of 
 study designs and analytic methods associated with cer / re . 
 a systematic content review was 
 done to extract relevant information.results : according to key informants , randomization will remain an essential 
 component for assessing comparative or relative effectiveness . 
 they anticipate greater use 
 of policy levers such as conditional reimbursement or prior authorization to manage 
 diffusion of new drugs . 
 case studies provided important insights into situations when 
 certain types of cer evidence may be acceptable ( e.g. , observational data when differences 
 between drugs are largely convenience).conclusions : industry perceptions that cer / re will change payers ' 
 evidentiary requirements in the future are consistent with our findings 
 . growing 
 investment in payers ' own data and increased reliance on policy tools to control diffusion 
 of new drugs may also influence the type of evidence industry will be required to produce 
 by 2020 .