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1、White PaperAttracting Investment in Clinical Development How pharmaceutical companies make clinical development location decisions,and what healthcare policy makers can do to attract commercial clinical investment.SARAH RICKWOOD,Vice President,EMEA Marketing and Thought Leadership,IQVIA FIONA PEREIR

2、A,Engagement Manager,Brand&Integrated Research Solutions,IQVIA CAMILA ABELLA GMEZ,Intern,EMEA Thought Leadership,IQVIA Table of contentsExecutive summary 1Clinical trials:A global overview 4 Economic and societal impact of investment in commercial clinical development 4 Global landscape and trends 5

3、Investment criteria framework:Main drivers 7Country archetypes and relative attractiveness 11 Country archetypes 11 Country relative attractiveness:Interviewees perceptions 13Implications and recommendations 16Methodology 18References 19About the authors 21Attracting Investment in Clinical Developme

4、nt |1Executive summaryDeciding where to locate clinical trials is a critical and multi-layered investment decision for pharmaceutical companies.Understanding the country selection criteria pharmaceutical companies use is essential for Government policy makers,Regulators and Health authorities to att

5、ract clinical inward investments which will generate economic,healthcare and societal value for their local population.This white paper is based on interviews with senior decision makers in pharmaceutical companies responsible for the choices that their companies make about where to locate clinical

6、development.From these interviews,we analyse industry trends and create an Investment Criteria Framework providing actionable recommendations for Regulators,Healthcare policy makers and providers and pharmaceutical companies.Despite growth in R&D investment,pharmaceutical companies increasingly face

7、 challenges to deliver successful and time-efficient drug developments.Success rates,as measured by IQVIAs Clinical development Productivity index,have fallen significantly since 20151,with a wide range of issues to blame.These include trialling increasingly complex therapeutics in increasingly defi

8、ned patient populations,and growing competition for investigator sites and patients in therapy areas,such as oncology,with high levels of innovative activity.They also can include,dependent on country,regulation which slows the set up and execution of trials,and absence of modern digital healthcare

9、infrastructure that can speed patient identification and recruitment.It is critical for a countrys healthcare system policy makers to understand the challenges that pharmaceutical companies face when conducting clinical trial to ensure their health system provides differentiated value and attracts m

10、ore clinical inward investment.This white paper provides an Investment Criteria Framework with the key factors that pharmaceutical companies assess to decide in which countries to locate their clinical trials,both early and late stage,and the relative attractiveness of different regions and countrie

11、s against those criteria.These results were derived from anonymous interviews to Heads of Global Clinical Operations and/or Regulatory Affairs of 60%of Large pharmaceutical companies(defined as those in the top 20 of global prescription medicine revenues)and complemented the study with interviews to

12、 European mid-sized pharma,and Emerging Biopharma companies(EBPs).This white paper makes strategic recommendations for policy makers and policy influencers by country archetype,with actionable initiatives to accelerate clinical trial activity and promote clinical inward investment.2|Attracting Inves

13、tment in Clinical DevelopmentMultiple reports conclude that clinical trials provide large economic,healthcare system and societal value for countries.In 2021,the top 15 largest pharmaceutical companies by revenue invested$133 billion in R&D expenditure(7.6%CAGR from 2016).2 44%of total R&D investmen

14、t was allocated for clinical trials,of which 27%were invested in Phase III.3 US,EU4,UK,Japan,and China hosted 60%of global clinical trials registered in Clinicaltrials.gov in March 20224 and accounted for 77%of global sales in FY2021(IQVIA MIDAS,List price,Rx Only).“Other European”countries conducte

15、d 13%of global clinical trials and“Other non-European”countries hosted 27%of global clinical trials,suggesting a clear attractiveness for clinical trials despite their smaller commercial opportunity (i.e.,23%of global sales in FY2021).In recent years,some pharmaceutical companies have narrowed the n

16、umber of sites and countries in clinical trials to minimise complexity and increase success rates which have declined to 5%across all therapy areas in 2021.5 The underlying drivers are multi-factorial,but pipeline focus on highly specialised treatments for rarer indications,bringing with it increase

17、s in trial complexity,is a common factor.It is critical for policy makers to understand the challenges that pharmaceutical companies face conducting clinical trial if they wish to attract more clinical inward investment.This white paper analyses industry trends and provides an Investment Criteria Fr

18、amework based on our interviews with Heads of Global Clinical Operations and/or Regulatory Affairs.Our research shows a complex combination of decision drivers for country selection,including Commercial return from the country,trial performance,clinical expertise network,regulatory framework,and dis

19、ease prevalence.Cost of trial drivers were discussed by interviewees but were not identified as a top priority in the individual country selection criteria(i.e.,“quality and speed over costs”or“cost is a consequence of other more relevant factors”).However,as the country set used for a trial will in

20、fluence overall trial cost,its sometimes possible that country adjustment will come into play at that point.In short,while some factors such as commercial market size and disease prevalence are largely not influenceable by country policy makers,many factors driving clinical investment decisions are,

21、and factors related to speed,quality and expertise prevail,at the individual country level,over cost.Pharmaceutical companies establish pre-defined lists of countries,or country archetypes,based on strategic objectives and internal policies:“Cornerstone”countries are defined by commercial and strate

22、gic priorities and always include US,EU4,UK,Japan,and China,“Growth”countries are over 150 countries which are considered as optional locations,and“Out-of-scope”countries,where no clinical trials are conducted by the companies we interviewed except in exceptional circumstances such as disease preval

23、ence in those countries constituting all or a Multiple reports conclude that clinical trials provide large economic,healthcare system and societal value for countries.In 2021,the top 15 largest pharmaceutical companies by revenue invested$133 billion in R&D expenditure(7.6%CAGR from 2016).2 44%of to

24、tal R&D investment was allocated for clinical trials,of which 27%were invested in Phase III.3 |3significant part of global prevalence.While Cornerstone countries will always be considered,policymakers in the very large“Growth”group of countries must understand how they can move up the list pf priori

25、ties,and countries currently“Out-of-scope”how they can move into the“Growth”category.Additionally,this white paper provides the interviewees perceptions about countries relative attractiveness at a global level(i.e.,US,EU4+UK,China,Japan,META,and Australia)and at a European level(i.e.,Germany,UK,Spa

26、in,CEE,and Nordics).Our white paper makes specific recommendations for healthcare policy makers in countries falling into the different country archetypes.For“Cornerstone”Countries,an“Accelerate and Collaborate”strategy will help these countries,most likely to be the site of clinical investment,to c

27、apture more share amongst core countries by providing agile and innovative research ecosystem,local regulation which enables rather than hinders clinical trial set up,digital investment to support novel clinical trials design and specialised capabilities,and cross-country agency collaboration to unl

28、ock optimization of global R&D.For“Growth”Countries,a“Differentiate and Attract”strategy is necessary,defining strategic positioning in global clinical trials versus other“Growth”countries based on internal capabilities assessments to identify main source of clinical value-add.Policy makers should a

29、lso design short-term(e.g.,experts network activation,patient awareness,etc.)and mid-term initiatives(e.g.,health systems,niche development,etc.)to build relationships and attract more clinical inward investment.Policy makers in“Out-of-scope”Countries:“Ticket-to-Play”countries need to identify addre

30、ssable causes for being out of scope and understand the minimum standards required to be considered by pharmaceutical companies and start designing and building the basic digital capabilities and infrastructure to advance towards better healthcare delivery.Pharmaceutical companies must also be activ

31、e collaborators in countries development of clinical trial infrastructure and capacity,through proactive collaboration with Agencies and Associations,feedback,advocacy and support during the development and implementation of new clinical regulatory framework,continuous internal optimisation and inve

32、stment in digital solutions(e.g.,DCT),“Patient voice”as active drivers of trials journeys and protocols designs,Diversity and Inclusion initiatives,etc.In recent years,some pharmaceutical companies have narrowed the number of sites and countries in clinical trials to minimise complexity and increase

33、 success rates which have declined to 5%across all therapy areas in 2021.5 4|Attracting Investment in Clinical DevelopmentClinical trials:A global overviewECONOMIC AND SOCIETAL IMPACT OF INVESTMENT IN COMMERCIAL CLINICAL DEVELOPMENTIQVIA Institutes R&D Report 2022 estimated that the top 15 largest p

34、harmaceutical companies by prescription medicine revenues invested$133 billion in 2021 in R&D expenditure,up by 44%from 2016(Figure 1).6 A separate Pharmaceutical Research and Manufacturers Association America(PhRMA)study showed that of the total surveyed company financed global R&D investment,44%is

35、 allocated for Phase IIII clinical trials,a total of$40bn for a single year,2020,7 with Phase III representing$25bn of investment alone(Figure 2).8 Clinical trials provide huge economic and societal value for countries:early access to new therapeutic treatments for local patients,investment in and n

36、ew approaches to clinical infrastructure,for example,diagnostic testing,increased direct revenue for hospitals,and world-class talent attraction.9EMEA EXAMPLES OF ECONOMIC AND SOCIETAL IMPACT In Barcelonas Hospital Vall dHebron,clinical trials represented 18.5%of their total revenue streams in 2020(

37、7.46 M),after national grants and industry agreements,as published in annual reports.10 In the UK,IQVIA estimated that its 20%share of all commercial clinical trials the UK delivered 1.2bn of economic impact in 2020,based on information available in the National Institute for Health and Care Researc

38、h(NIHR)annual report 2020.11 IQVIA META(Middle East,Turkey,and Africa)estimated that even a 1%increase in global clinical trials market share would generate nearly 4,000 local jobs and help over 10,000 patients participating in trials benefit from cutting edge therapies.12Figure 1:Top 15 large pharm

39、a R&D spending,20162021,US$BnFigure 2:R&D by Function in PhRMA member companies,2020,in%44%of R&D investment allocated in clinical trials in 2020(27%allocated for Phase III)PhRMA Annual Survey$133Bn in 2021 in R&D expenditure by top 15 large pharma(7.6%CAGR from 2016)IQVIA InstituteSource:Pharmaceut

40、ical Research and Manufacturers of America,PhRMA Annual Membership Survey,2021.Source:IQVIA Institute R&D Trends 2022929732001920202021CAGR+7.6%Pre-clinicalApprovalPhase IVUncategorizedPhase IPhase IIIPhase II25%12%4%27%9%8%15%R&D Investment AllocationClinicaltrials Phase I-III

41、 44%|5GLOBAL LANDSCAPE AND TRENDS An obvious possible decision-making factor in the siting of clinical trials might be where commercial return is greatest,and indeed interviewees confirmed that the commercial potential of a county market is a consideration,especially when siting late phase clinical

42、trials,but analysis shows theres no exact match.Comparing the number of clinical trials registered in clinicaltrials.gov13 versus the total global prescription medicine sales in 2021(from IQVIA MIDAS,list price,Rx Only),both trial activity and commercial opportunity are highly concentrated in a smal

43、l number of countries.While the comparison is not exact,as reporting bias on clinical trials likely favours more developed countries,its clear that commercial potential and clinical activity are not perfectly correlated.Eight“Cornerstone”countries by interviewee consensus,US,EU4,UK,Japan,and China h

44、osted 60%of global clinical trials but generated 77%of global sales in 2021.“Other European”countries conducted 13%of global clinical trials,and“Other non-European”countries hosted 27%of the total(including Canada with 6%,South Korea with 3%,and Australia with 2%),suggesting a clear attractiveness a

45、s location for clinical trials despite their smaller commercial opportunity.Eastern European countries also take a greater share of clinical development activity than their commercial potential alone would predict.Clearly,there are factors other than simple commercial potential at play in the decisi

46、on-making process.IQVIA Institute R&D Trends 2022 report evidenced that success rate(measured as likelihood of progressing successfully through all development phases)has declined across all therapy areas to 5%in 2021 due to a wide set of drivers,including growing appetite for(or necessity of)clinic

47、ally high-risk developments with the rise of more complex,often specialty products being developed,higher efficacy and safety requirements,and interruptions in product manufacturing.14 Pharmaceutical companies have also progressively reduced the number of sites and countries in clinical trials,a tre

48、nd which started prior to the Pandemic,and is most likely a response to the increasingly specialised nature of the products under trial.2020 figures should Sources:Clinicaltrials.gov,March 2022,IQVIA MIDAS quarterly sales 2021(List price,Rx only)EU4+UKChinaJapanOthers EUOthers non-EUUS27%14%13%8%6%6

49、%9%15%16%37%46%2%Number of CT,clinicaltrials.gov,March 2022 Sales share FY2021,IQVIA MIDAS(List price,Rx only)Cornerstonecountries77%Figure 3:Number of CT share vs sales share by regionEight“Cornerstone”countries by interviewee consensus,US,EU4,UK,Japan,and China hosted 60%of global clinical trials

50、but generated 77%of global sales in 2021.6|Attracting Investment in Clinical DevelopmentFigure 4:Clinical trials elements of complexity indexed to 2010 values,all phases,20000001920202021SubjectsEndpointsEligibility criteriaAll comple

51、xityCountries(-11%)Sites(-20%)Source:Citeline Trialtrove,IQVIA Institute,Jan 2022.Global Trends in R&D:Overview through 2021.Report by the IQVIA Institute for Human Data.be regarded as atypical,since they combine massive increases in patient numbers(because of COVID-19 vaccine trials)with reductions

52、 in countries and sites that were driven by lockdowns and COVID-19 restrictions (Figure 4).While the trend to focus on a small number of countries for clinical trials might be understandable,it creates competitive challenges,both for the sites in those countries and for the companies running clinica

53、l trials.For the few countries in which pharmaceutical companies tend to retain clinical trials(i.e.,“Cornerstone”countries),concentration drives increase in competition and costs for sites and patient recruitment,higher burden and saturation in health systems and possibly longer administrative dela

54、ys.It is also likely to reduce the number of treatment nave patients in patient segments targeted by multiple agents in development and While the trend to focus on a small number of countries for clinical trials might be understandable,it creates competitive challenges,both for the sites in those co

55、untries and for the companies running clinical trials.launched.The countries outside the shrinking core will lose the benefits of clinical investment unless they can improve their attractiveness and move to the front rank of the large“Growth countries”segment by developing a clinical development inf

56、rastructure and environment which is differentiated and |7Investment criteria framework:main drivers Based on our interviews conducted with Heads of Global Clinical Operations and/or Regulatory Affairs of pharmaceutical companies in the Top 20,European mid-sized,and Emerging Biopharma(EBPs)segments,

57、we identified the following drivers for Investment Criteria:Condition Prevalence,Trial Performance,Expertise Network,and Regulatory Frameworks.Pharmaceutical companies prioritise these factors dependent on the underlying asset or study and also the size their footprint as a company.Interviewees did

58、mention clinical trial cost components as part of their criteria,but not as a top priority in country selection (i.e.,“we prioritize quality and speed over costs”or“cost is a consequence of other more relevant factors”).A.Prevalence pre-scoping Pharmaceutical companies utilise advanced algorithms an

59、d AI/ML to provide an initial scope of countries to consider.Assessments of epidemiologic data,most fundamentally incidence and prevalence of the condition but also diagnosis rates and ease of diagnosis,past and active clinical trials statistics,and even local nutrition and cultural are factors to d

60、efine the attractiveness and viability of a particular country in the studys protocol.B.Trial performance:Speed and quality Speed and quality are the main drivers for country selection criteria for clinical trials.Pharmaceutical companies face a highly competitive environment,in which speed is key t

61、o maximise product value and time on the market.Moreover,predictability of the forecasted timelines(e.g.,start-up procedure length,site activation speed,and patient recruitment lead times)is critical for the studys design and investment decisions.Patient recruitment is the key bottleneck our intervi

62、ewees identified to performance,both in“Cornerstone”countries,where market saturation exists and competition for patients is intense,and in“Growth”countries,where the speed and recruitment of patients varies greatly mostly for other,often Figure 5:Investment criteria framework:Main drivers assessmen

63、tSource:Clinicaltrials.gov,March 2022,IQVIA MIDAS Quarterly Sales 2021(List price,Rx Only),IQVIA VII Launch Excellence 2022.Include digital favourability Main decision drivers for country levelPrevalence pre-scoping:Data-driven assessment of patient population availabilityTrial performance:Speed and

64、 quality Expertise network:Knowledge and advocacy Regulatory framework:Value and innovation Set-up and activation timelinesPatient recruitment and retentionDiversity and rare diseases recruitmentDigitalisation,decentralised clinical trials,niche capabilitiesRole of KOLs and investigatorsEnd-to-end i

65、mpact of in market access and launch excellenceAssociations and advocacies,etc.Registration and approval policiesClinical trial design innovationAccess and reimbursementTax benefits,grantsCost components:not top-priority(i.e.,“quality and speed over costs”),might be relevant at international level f

66、or a given trial 8|Attracting Investment in Clinical Developmenthealthcare infrastructural,reasons.New technologies can provide timely solutions to optimise recruitment and clinical trial operations.For example,AI/ML driven solutions to take existing Electronic Healthcare record data and analyse it

67、to provide insights on patients who may fit clinical trial inclusion criteria,while maintaining patient privacy through measures such as placing software behind a hospitals own firewall,have been developed and are in active use in healthcare institutions.These can provide a competitive edge in“Growt

68、h”countries differentiating an institution,and,if widely adopted,a country,in an otherwise large pool of possible candidates.Decentralized Clinical Trials(DCT)are trials blending remote and site-based elements or conducted as fully remote studies15 and can be an operational solution which can addres

69、s low patient recruitment rates,proving to expand patient pools,improve recruitment and retention,and reduce burdens in logistics and costs.IQVIA Institutes Digital Health Trends 2021 report estimated a potential reduction of 4461%on-site visits in Phase II and III,for Decentralised Clinical Trials,

70、depending on the therapeutic area.16 Most of the companies we interviewed have so far conducted decentralization only in components of clinical trials,not fully decentralized clinical trials,but they anticipate the direction of travel to be to greater use.Hybrid clinical trials enable pharmaceutical

71、 companies to compete in attracting patients by offering a differentiated and attractive patient journey particularly relevant in indications and countries where recruitment competition is very high and for rare diseases and indications with logistically complex recruitment.One of the factors impedi

72、ng the adoption of more effective operational models is the wide disparity in countries healthcare system digital maturity,from strategy,infrastructure,and implementation.IQVIA EMEA Thought Leaderships white paper“Switching On the Lights”benchmarks digital health systems across EMEA and proposes rec

73、ommendations by country archetypes(Figure 6).17 Health systems undoubtedly are moving in the same direction with respect to Figure 6:Digital health system:Digital maturity archetypes Source:IQVIA Thought Leadership,Jan.2022.ImplementationscoreInfrastructurescoreARCHITECTSPlanning greatly outweighs a

74、ny implementedmeasurersHIGH3LOW3LOW3HIGH3HIGH3LOW3HIGH3HIGH3HIGH3BUILDERSWell-built infrastructure thatis currently underutilisedOPERATORSEstablished digital baseallows for real applicationsof digital healthcareIncentivesscoreDigital maturity score112345 |9digital maturity,but their current level of

75、 digitisation,and therefore attractiveness for Decentralised Clinical Trials,is broad.Countries which develop robust digital infrastructure fast will be those best positioned to win a larger share of clinical development activity in the future.Improving Diversity and Inclusion(D&I)in clinical develo

76、pment was a topic elevated in importance by the Pandemic,and Regulators,lead by the FDA,are imposing stricter criteria for patient selection to right the historic wrong of under-representation of ethnic and minority populations.The FDA demands on reflecting diversity of the actual disease population

77、 under study have driven up demand for US-based clinical trials,making“decision increasingly defined by demands of regulators”.Other Regulators,specially from“Cornerstone”countries,are expected by our interviewees to follow these diversity requirements.Countries where straightforward recruitment of

78、diverse populations meeting regulator expectations will have another element of advantage.C.Expertise network:Knowledge and advocacy Some Emerging Biopharma companies(EBPs)and mid-sized pharmaceutical companies prioritize access to the expertise network over clinical trial speed,to build early relat

79、ionships with local stakeholders in target markets.The need for knowledge and access to networks becomes increasingly important when entering a new therapeutic area as an unknown,as EBPs which account for the 65%of molecules in R&D pipeline,80%being single-assets developments,18 are more likely do.T

80、o increase attractiveness as a trial destination for these types of company,country policy makers must explore how they can facilitate an attractive local knowledge network for key therapeutic areas and support entrant company access to R&D hubs.For Large pharma,the role of Key Opinion Leaders(KOLs)

81、and influential Investigators is also very valuable.Clinical operations and strategic committees are increasingly considering the end-to-end vision of the R&D process and are assessing how the design of the protocols of clinical trials will impact more downstream processes,such as Market Access and

82、Launch Excellence.However,companies mentioned a need for an“strategic balance”to access Expertise Networks without compromising the speed of clinical trials.Some KOLs were not described as“fast recruiters”,and some have competing commitments with other pharma companies.Thus,companies do not always h

83、ave a systematic approach to engage with KOLs and carefully define their specific roles in the study(e.g.,design advisor,steering committee,spokesman,etc.).D.Regulatory framework:Value and innovation Regulators can catalyse clinical trial optimization and innovation by launching ambitious initiative

84、s,accepting novel designs and use of real-world evidence.19 In January 2022,the EMA launched the Accelerating Clinical Trials initiative in the EU(ACT EU)20 to replace the often-criticised EU clinical trials directive widely seen by the industry as a slowing clinical development in Europe.In the UK,

85、the MHRA initiated an eight-week consultation in January 2022 to design a“world-class sovereign regulatory environment”for clinical trials.21 Some Emerging Biopharma companies(EBPs)and mid-sized pharmaceutical companies prioritize access to the expertise network over clinical trial speed,to build ea

86、rly relationships with local stakeholders in target markets.10|Attracting Investment in Clinical Development In the US,the FDA outlined new strategies to modernize clinical trials,for example,advancing precision medicine,22 in 2019,and developed guidance to enhance the diversity of clinical trial po

87、pulations and procedures for Emergency Use Authorization(EUA)and accelerated approval pathways.Chinas NMPA recently unveiled a 5-Year-Plan to synchronize with Global Drug Approval,proposing rolling data submissions,and published a draft document to accelerate the review of new drug applications(NDAs

88、).23 Globally,an increasing range of clinical trial designs were used to support regulatory submissions in 2021,reflecting the diversity of therapeutic innovation approaches to clinical development.For instance,“embracing a seamless path that bypasses the traditional stepwise development paradigm of

89、 standalone sequential Phase I,II and III trials”,as described in IQVIA Biotechs white paper,“Innovative Design in Early Phase Oncology Studies in JAPAC”.24 The pharmaceutical industry welcomes these ambitious initiatives for standardisation in criteria and approval procedures and praise an open app

90、roach to consultation and co-creation.However,pharmaceutical companies have expressed their concerns about how these implementations will unfold,especially in highly decentralised countries,and how they will address other critical challenges,such as highly restrictive paediatric clinical trials.Acce

91、ss and Reimbursement is another factor considered when assessing local regulatory frameworks,and companies may use the EFPIA Patients W.A.I.T.Indicator Survey to identify product availability by approval year,rate and time of availability,etc.25 Finally,tax credits and grants may act as incentives a

92、nd attract some companied to conduct local clinical trials in some countries,for example,Canada and Portugal,but these are not considered a decisive factor for country selection by our interviewees from pharmaceutical companies.E.Cost considerations Cost components of trials were not identified as a

93、 top-priority criteria for assessing individual countries in most of our interviews.Even if rigorous cost analysis is performed by companies when assessing trial location,the pressure for fast-speed and high-quality clinical trials drives the final decisions.Comments such as“Time is the most expensi

94、ve commodity”and“every month missed from forecast costs a lot of money”reflects pharmaceutical companies need and willingness to pay for accelerate and certain clinical trial timelines.Countries which can deliver speed,by this logic,will be more attractive than those that deliver lower cost but no s

95、peed advantages.At the aggregate level,when assessing the cost of a given trial over the basket of countries chosen,cost components may come into consideration and lead to readjustment of the country group.Cost components of trials were not identified as a top-priority criteria for assessing individ

96、ual countries in most of our interviews.Even if rigorous cost analysis is performed by companies when assessing trial location,the pressure for fast-speed and high-quality clinical trials drives the final |11Country archetypes and relative attractiveness COUNTRY ARCHETYPESMost pharmaceutical compani

97、es we interviewed have pre-defined lists of countries for clinical trials based on their own strategic goals and internal policies which we refer to as“Cornerstone”,“Growth”and“Out-of-scope”country archetypes in this white paper.I.“Cornerstone”countries“Cornerstone”countries are defined by the comme

98、rcial and strategic priorities of each company(i.e.,US,EU4,UK,Japan,and China).These eight“core countries”are identified in IQVIAs Launch Excellence Series as pivotal for launch success.26 They hosted 60%of global clinical trials registered in clinicaltrials.gov and generated 77%of global prescripti

99、on medicines sales in 2021 reported by IQVIA MIDAS.Pharmaceutical companies described these countries as“must-go”and they will conduct clinical trials in these countries despite their highly competitive and saturated clinical trial environment,complex and stricter regulatory requirements,sometimes l

100、engthy registration and approval timelines,and higher costs.The types of product for which trials are conducted tends to reinforce the status of these Cornerstone Countries-for Cell,Gene and other advanced therapies these countries are most likely to possess the infrastructure necessary to support t

101、hese trials.Within this group of countries there is,however,change in the share of inward investment captured.In 2021,EU-headquartered companies R&D pipeline share reduced from 31%to 25%in past 15 years while China rose to 12%up from 4%in 2016(Figure 8).27 Chinas increase in share is mainly driven b

102、y the governments regulatory reforms and massive investments in innovation development,while Europes decline may be explained by the unattractive and complex perceptions on its clinical trials directives(expected to improve by the EMAs new initiatives,ACT EU,launched in January 2022).The US holds it

103、s share,driven by a strong perception that the FDA is friendly to Cell,Gene and RNA innovation.E.g.;US,EU4,UK,Japan,and ChinaE.g.,:Canada,South Korea,Australia,Belgium,Netherlands,Denmark,Sweden,Poland,other Eastern European countriesExamplesDescription“Out-of-scope”countries“Growth”countries“Corner

104、stone”countriesArchetypeE.g.:Most low income countries in Africa,Asia,South AmericaEthical concerns:No CT in countries with no commercial intent(few exceptions for rare diseases,or those largely prevalent in these countries),(for some)high corruption index,etc.Geopolitical factors:Issues affecting C

105、T stability and continuity.+150 countries.40%of global CT in clinicaltrials.gov.Three tiers identified by number of clinical trials in 2022Multiple local agencies and regulations,creating need for global cooperation initiatives8“Cornerstone”countries prioritised by commercial priority:60%of total CT

106、,77%of global prescription medicine sales in 2021(List price,IQVIA MIDAS)Highly competitive and saturated markets.Diversity regulations apply.Changes in their share of inward investment capturedFigure 7:Clinical investment country archetypes.Pre-defined country lists identified:“Cornerstone”,“Growth

107、”,and“Out-of-Scope”country archetypesSource:Clinicaltrials.gov,March 2022,IQVIA MIDAS Quarterly Sales 2021(List price,Rx Only),IQVIA VII Launch Excellence 2022.12|Attracting Investment in Clinical DevelopmentNot only is it the worlds most valuable pharmaceutical market,the US typically accounts for

108、60%or more of the cumulative first five year sales of New Active Substances.28Emerging Biopharma(EBPs)also play an important role in the global share of pipeline since they accounted for the 65%of molecules in R&D pipeline in 2021.29 Chinas EBPs accounted for 17%of the overall EBP innovation pipelin

109、e in 2021,up from 6%just five years ago while both US and Europe-based companies have lost share over the same period.II.“Growth”countries Pharmaceutical companies we interviewed considered other+150 countries as optional locations which we refer to as“Growth”countries.Companies assess each country

110、under rigorous data-driven analytics to identify the most optimal location,depending on a political,economic,and digital infrastructure considerations.“Growth”countries hosted 27%of total number of clinical trials in March 202230 but they widely differ in levels of activity,in terms of patient numbe

111、rs.This is often a function of the disease area for which trials are Figure 8:Country share of pipeline Phase I to regulatory submission based on company headquarter location,20062021Table 1:“Growth”country tier,number of clinical trials registered,March 2022.Source:IQVIA Pipeline Intelligence,Dec 2

112、021,IQVIA Institute,Jan 2022.Global Trends in P&D;Overview through 2021.Report by the IQVIA Institute for Human Data Science.Source:Clinicaltrials.gov,March 2022.“GROWTH”COUNTRY TIERSNUMBER OF CLINICAL TRIALS(Registered in clinicaltrials.gov)EUROPEROWTIER 1(20 countries)4000 CTBelgium,Netherlands,De

113、nmark,Poland,Switzerland,Sweden,Austria,Russia,Hungary,and NorwayCanada,South Korea,Australia,Israel,Brazil,Turkey,Taiwan,Egypt,India,and MexicoTIER 2(13 countries)2000 4000 CTGreece,Finland,Romania,Portugal,Ukraine,and BulgariaArgentina,South Africa,Thailand,Singapore,Hong Kong,Puerto Rico,and New

114、ZealandTIER 3(+120 countries)2000 CTRest of countriesRest of countries43%2%2%11%31%44%3%3%11%30%46%4%3%11%28%44%6%4%12%25%50%45%40%35%30%25%20%15%10%5%0%2006201120162021U.S.EuropeJapanChinaSouth KoreaAll others |13conducted in these countries;large numbers of patients can be recruited for trials for

115、 specific disease areas where these countries have a large pool of,for example,treatment nave patients,but they may see no trial activity in other areas,for example,those where cell and gene therapies are being trialled.Cornerstone countries,in contrast,tend to be strong across disease areas.These“G

116、rowth”countries show a clear attractiveness for clinical trials despite accounting for 14%of global sales(IQVIA MIDAS,list price,Rx only).In many cases,attractiveness for clinical trials is well in advance of commercial performance,as for some Eastern European countries.However,ex-EU Growth countrie

117、s have their own local regulators,creating a need for global cooperation initiatives for clinical trial optimisation(e.g.,Orbis Open Research Biopharmaceutical Internships Support31)and cross-country clinical trial standardisation(i.e.,registration forms,data transfer,import/export,etc.).III.“Out-of

118、-scope”countries This list of“Out-of-scope”countries is defined by internal policies driven by ethical concerns and geopolitical factors.Following ethical codes of conduct,some companies do not conduct clinical trials in countries where they have no intention to commercialise(with few exceptions for

119、 rare diseases)or in countries with high fraud and corruption index,etc.Geopolitical issues affecting stability and continuity of clinical trials may cause trials to be paused or cancelled,depending on the local situation.For example,some pharmaceutical companies have suspended new patient recruitme

120、nts and clinical trial site activations in Ukraine,Belarus,and Russia,while continuing to provide essential medicines and vaccines and drugs to patients already enrolled in studies.32 These lists are revised and updated periodically to reflect the status of the countries.COUNTRY RELATIVE ATTRACTIVEN

121、ESS:INTERVIEWEES PERCEPTIONSCountry qualitative perceptions were collected during the interviews at a global and European level.The following perceptions are specific to each interviewee and reflect current events shaping clinical trials as of March 2022.I.Global perceptions The following are the ma

122、in perceptions of pharmaceutical company interviewees at a global level.As main takeaways:For the US,the FDA is recognized as the leader for innovation providing“clear-cut criteria”.However,the attractiveness provided by an optimised regulatory framework is offset by the saturated and costly“on-grou

123、nd”site activities(e.g.,recruitment is difficult,high competition and costs,low negotiation bargain,etc.).Companies are therefore caught in a double bind with the US:they must include it and it is also competitive and expensive to run trials.In the EU4+UK,the industry welcomes the implementation of

124、new clinical trial initiatives to replace the former clinical trials directive,expecting a boost of EUs clinical trials attractiveness by standardisation,reduction of large disparities withing local Ethics Committees,reduction long delays for registration and approval,especially in decentralised cou

125、ntries,etc.China has achieved“significant progress”in NAS Launch but its dynamic regulatory landscape represents a struggle to keep updated,“even for local expert”.14|Attracting Investment in Clinical DevelopmentFigure 9:Country relative attractiveness:Global perceptionsSource:Interviews,EMEA Though

126、t Leadership.Country relative attractiveness:Global perceptionsGlobal perceptions onclinical trials In Jan.2022,EMA launched Accelerating Clinical Trials(ACT EU)and MHRA launched consultation for optimisation of CTLow harmonisations of application assessment and approvalsLarge disparities across loc

127、al Ethics Committees,can create long delays,specially in decentralised countriesStringent data protection regulations as required by GDPR,and no homogeneous data flow across member countriesUncertainty for new regulations implementation and sense of potentially“making the process more complex”Divers

128、ity and inclusion on agenda,but not advanced as FDAEU4+UKUSFDA recognized as leader for innovation providing“clear-cut criteria”High in transparency and innovation while protecting the public“Very saturated market”with difficult onground site activities:recruitment is difficult,high competition and

129、costs,low negotiation bargain,etc.In 2019,FDA outlined strategies to modernize CT and has improved data and clinical recordsUS demands on reflecting diversity of local population has been“driving up demand”for the US clinical trials but has also triggered“patient recruitment barriers and unfeasible

130、long timelines”Increasing attractiveness due to recent changes in regulation and large mature sites availability Untapped patient potential(research nave)META:Middle East,Turkey,and AfricaStrong early phase player for clinical trials with strong FDI initiatives“Not highly attractive for reimbursemen

131、t but strong for early(PI/II)clinical trials(and exporting data)”AustraliaHigh-quality medical facilities,government financial incentives for clinical trials,high costs but strategic importance of Asian consumer markets.Entry with local partners.“Good recruitment for large nave population”“Significa

132、nt progress”.In 2021,surpassed Japan in NAS Launch numbers.In 2022,NMPA launched a 5-Year-Plan to synchronize with Global Drug ApprovalHurdles in clinical study ethics committee review while leaving out other restrictions including genetic material export and substandard clinical sitesProposed rolli

133、ng data submissions to incentivize development of innovative new drugs and accelerate its approval.“Dynamic regulatory landscape that local experts struggle to keep updated”ChinaJapanII.European breakdown The following are the main perceptions of the interviewees of the most-mentioned European count

134、ries in the interviews.The following list is presented in descending order of pharmaceutical market value it aims to reflect the diverse perspectives of the pharmaceutical companiess senior executive representatives during the first quarter of 2022.Each country is identified with a“Digital Maturity

135、Archetype”,defined in the IQVIAs Thought Leadership white paper“Switching On the Lights”,in which recommendations are presented for each country archetypes.33 |15Figure 10:Company interviewee perceptions of European countriesSource:Interviews,EMEA Thought Leadership.*Note:Archetypes from IQVIA Thoug

136、ht Leaderships white paper“Switching On the Lights:Benchmarking digital health systems across EMEA”analyses and proposed recommendations by country archetypes.COUNTRY DECSRIPTIONDIGITAL MATURITY ARCHETYPE*INTERVIEWEES PERCEPTION Germany:Increased complexity and variation in approval process(e.g.,var

137、iability on Ethics Committees,“IRBs more complicated,more pushback and longer and timelines”).Introduced laws stating voluntarily opt-in to uploading their health data,seen as hampering the adoption of EHRs.Revamped digital health strategy to accelerate path but lack of incentives or legal structure

138、Builder UK:Highly centralised health system in NHS England,with capacity for decentralised clinical trials.Some respondents concern for current system exhaustion and patient backlog.Strong investments in Biotech Hubs and AI to analyse health data on a national scale and attract top-tier talent.Large

139、 opportunity in Omics and a proposed new-born screening programme.Operator Spain:Increased attractiveness due to new regulation(i.e.,“Spain absolute collaboration and dedication”,“Shining light”).Collaborates with Pharmacos as advocates for CT.Recruitments speed varies greatly depending on investiga

140、tors.Comprehensive digital laws but uneven implementation at regional levels.Need to improve CTA approval timelines follow-up questions clarity.Architect Nordics:Cultural disposition towards ambitious projects such as whole genome sequencing at a national scale(perceived value in sharing their data)

141、.Widespread use of telehealth solutions and AI public sector projects.Omics renowned nationwide programme of whole genome sequencing 60k patients by 2024 and led by the Danish National Genome Centre.Operator Other CEE:Region has historically been,and remains,highly attractive for clinical developmen

142、t.Perceptions of increase in number of trials and patients in other CEE countries to offset impact of Ukraine crisis.Fast patient recruitment,high-quality sites and investment in digitisation are main drivers.Poland launched revival plan of 500mn for digitisation though remains“slow approving CTAs”.

143、Architect UKR:Ukraine historically very attractive for clinical trials due to high availability of patients and health system expertise.Company policies to temporarily suspend new patient recruitments and clinical trial site activations as response to Ukraine crisis.Future status uncertain.Architect

144、16|Attracting Investment in Clinical DevelopmentImplications and recommendationsThe pharmaceutical industrys global clinical investment will continue to evolve because of multiple complex investment drivers.However,policy makers in country health systems can play a critical role in improving country

145、 attractiveness for inward clinical investment.Clinical trials are undergoing rapid changes because of digitisation,decentralisation,and diversity and inclusion drivers,alongside the trend to ever more advanced innovation being trialled.Policy makers seeking to attract clinical trial investment must

146、 respond to these trends by shaping health systems to be able to support these clinical trial needs and pharmaceutical companies can help shape policy by advocating for the changes they find most helpful and working with health systems to deliver on them.The following strategic recommendations for r

147、egulators and industry associations(e.g.,EFPIA,ACRO)provide actionable initiatives to accelerate clinical trials and promote clinical inward investment by country archetype:“Cornerstone”countries:“Accelerate and Collaborate”strategy aims to capture more share amongst core countries by providing agil

148、e and innovative research ecosystem:Correct implementation of new local regulations(i.e.,EMAs ACT EU and MHRAs initiatives)with close follow-up and co-creation with pharmaceutical companies and industry associations Digital investment to support novel clinical trials design(i.e.,DHS,DCT),niche capab

149、ilities (e.g.,omics)to support pioneering clinical breakthroughs Cross-country agency collaboration to unlock optimization of global R&D Building on the already established advantage these countries have in providing a strong infrastructure for Cell,Gene and other advanced medicinal product trials.F

150、igure 11:Main recommendations:Regulators and associations Actionable initiatives by country archetypeSource:EMEA Thought LeadershipWorkstreams to boost clinical trials in METAEuropes mid-sized pharma face the 2020Further IQVIA referencesActionable recommendations“Out-of-scope”countries“Growth”countr

151、iesCountry archetypeStrategic goal“Accelerate andcollaborate”“Differentiateand attract”“Ticket-to-play”“Cornerstone”countriesR&D Trends Report 2022Ethical concerns:No CT in countries with no commercial intent(few exceptions for rare diseases,or those largely prevalent in these countries),(for some)h

152、igh corruption index,etc.Geopolitical factors:Issues affecting CT stability&continuity.+150 countries.40%of global CT in clinicaltrials.gov.Three tiers identified by number of clinical trials in 2022Multiple local Agencies and regulations,creating need for global cooperation initiativesImplementatio

153、n of new local regulations(i.e.,ACT EU,MHRA)with close follow-up and co-creation with pharmacos and associationsDigital investment to support novel clinical trials design(i.e.,DHS,DCT),niche capabilities(e.g.,omics)to support pioneering clinical breakthroughs Cross-country agency collaboration to un

154、lock optimization of 60%global CTHealth Tech Trends 2021JAPAC innovative designOmics Investment 2022*CTQ opportunities |17 “Growth”countries:“Differentiate and Attract”strategy focused on developing a strong position to attract clinical trials by providing differentiated value based on internal asse

155、ssments and definition of roadmap:Perform internal assessments to identify main source of valuable offerings from the main drivers identified in the Investment Criteria,e.g.,population/prevalence identification,systems and data maturity,CT sites past performance,HC system capacity,niche capabilities

156、 Define strategic positioning in global clinical trials vs other“Growth”countries(e.g.,use of matrix performance vs.expertise for competitive benchmark)and build solid offering to capture the attention of pharmaceutical companies(e.g.,Nordics offering for Omics and fully integrated healthcare data,A

157、ustralia for early phase trials).Roadmap design of short-term(e.g.,experts network activation,patient awareness,etc)and mid-term initiatives(e.g.,health systems,niche development,etc.)to build relationships and attract inward investment from pharmaceutical companies “Out-of-scope”countries:“Ticket-t

158、o-Play”strategy suggests identifying causes and minimum standards required to be considered by pharmaceutical companies and start designing and building the basic digital capabilities and infrastructure to advance towards a better healthcare delivery.IMPERATIVES FOR PHARMA COMPANIESPharmaceutical co

159、mpanies also play their role in shaping policies which improve attractiveness of a country for clinical trial investment.In some instances,for example,in the formulation of the UK Life Sciences Strategy post BREXIT,circumstances provide a window of opportunity to be listened to by,and engage with,go

160、vernment.But for all countries,continuous work with policy makers both as individual companies but also collectively via industry associations is crucial.Key recommendations for pharmaceutical companies to shape the future of clinical trials are:Open approach and flexibility in the review of countri

161、es and sites to identify new opportunities and capabilities offered by countries and assess new business cases(i.e.,cost-benefit analysis).Proactive collaboration with agencies and associations and timely conversations to design innovative policies(e.g.,MHRAs consultation).Quantify value of pharma i

162、ndustry in local countries and convey benefits clearly(i.e.,non-technical language,focus on jobs created,benefits to patients).Support and constant feedback during implementation of new initiatives(e.g.,EMAs ACT EU 2022)and lead pioneering novel designs and products to find the right“Product-Policy”

163、combinations.Continuous internal optimisation of clinical trials and investment in digital solutions to unlock operational bottlenecks and build competitive advantages in patients journey(e.g.,DCT for patient recruitment and retention and reduction of logistics burden in clinical trials)and consider

164、 advanced technologies such as blockchain and advanced analytics in EMR.“Patient voice”as active driver of trial journeys and protocol designs and build strong collaborations with well stablished local advocacy groups to capture insights and provide tailored solutions for patients journey.Diversity

165、and Inclusion initiatives to reflect real patient population profile and underrepresented ethnic and minority populations by implementing processes and technologies to conduct optimised inclusive clinical trials and gain a valuable advantage in registration and approval of clinical trials.18|Attract

166、ing Investment in Clinical DevelopmentFor this study we undertook primary market research to identify the clinical investment criteria through hour-long qualitative interviews with high-profile pharma executives with investment decision power:Global Heads of Clinical Operations and/or Heads of Regul

167、atory Affairs located in US,UK,France,Germany,Spain,Switzerland,Australia,during 1Q 2022.Representatives from 60%of Top 20 Large pharmaceutical companies were interviewed to reflect the main drivers of spending in global clinical trials.European mid-sized pharma and Emerging Biopharmas(EBPs,defined

168、as those with less than$500 million in annual sales and R&D spending less than$200 million per year)were also interviewed to complement with insights and challenges from different-sized companies.Additional interviews to Associations(i.e.,EFPIA and ACRO)and internal IQVIA experts were conducted to d

169、esign the discussion guide and complement the analysis and recommendations.Secondary research from IQVIA Institute reports,MIDAS,R&D pipeline intelligence and external industry Associations and official Health Institutions reports.Methodology |19References 1.IQVIA Institute R&D Report 2022 https:/ 2

170、.IQVIA Institute R&D Report Institute 2022 https:/ 3.PhRMA Member Companies 2021 report https:/phrma.org/-/media/Project/PhRMA/PhRMA-Org/PhRMA-Org/PDF/M-O/PhRMA_membership-survey_2021.pdf 4.Clinicaltrials.gov,March 2022 https:/clinicaltrials.gov/ct2/search/map 5.IQVIA Institute R&D Report Institute

171、2022 https:/ 6.IQVIA Institute R&D Report Institute 2022 https:/ 7.It is noteworthy that whilst 2020 was an exceptional year because of the Pandemic and vaccine trials,overall spend growth of 9.8%was not exceptional relative to historic norms,so this spend level can be regarded as representative of

172、usual spending levels 8.PhRMA Member Companies 2021 report https:/phrma.org/-/media/Project/PhRMA/PhRMA-Org/PhRMA-Org/PDF/M-O/PhRMA_membership-survey_2021.pdf 9.FarmaIndustria Clinical Trials Economic Impact in Spain,April 2019 https:/www.farmaindustria.es/web/otra-noticia/el-positivo-impacto-econom

173、ico-de-los-ensayos-clinicos-en-las-cuentas-del-sistema-sanitario/10.Hospital Vall dHebron 2020 annual report http:/annualreport2020.vhir.org/facts-and-figures/vhir-statistics/economic-summary/11.NIHR annual report 2020 https:/www.nihr.ac.uk/documents/annual-report-20192020/26565 12.IQVIA META CT htt

174、ps:/ 13.Clinicaltrials.gov,March 2022 https:/clinicaltrials.gov/ct2/search/map 14.IQVIA Institute R&D Report 2022 https:/ 15.IQVIA Decentralized Trials 2022 https:/ 16.IQVIA Digital Health Trends 2021 https:/ Investment in Clinical DevelopmentReferences 17.IQVIA Digital Health Systems https:/ 18.IQV

175、IA Institute R&D Report 2022 https:/ 19.IQVIA Institute R&D Report Institute 2022 https:/ 20.ACT EU 2022 https:/www.ema.europa.eu/en/documents/regulatory-procedural-guideline/accelerating-clinical-trials-eu-act-eu-delivering-eu-clinical-trials-transformation-initiative_en.pdf 21.MHRA Consultation 20

176、22 https:/www.gov.uk/government/consultations/consultation-on-proposals-for-legislative-changes-for-clinical-trials/proposals-for-legislative-changes-for-clinical-trials 22.FDA Modernization of CT https:/www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-str

177、ategies-modernize-clinical-trials-advance 23.China CDE https:/ 24.IQVIA Early Stage JAPAC https:/ 25.EFPIA WAIT Indicator Survey https:/efpia.eu/media/636821/efpia-patients-wait-indicator-final.pdf 26.IQVIA LE VII https:/ 27.IQVIA Institute R&D Report 2022 https:/ 28.https:/ 29.IQVIA Institute R&D R

178、eport 2022 https:/ 30.Clinicaltrials.gov,March 2022 https:/clinicaltrials.gov/ct2/search/map 31.Project ORBIS in a nutshell https:/orbisproject.eu/index.php/orbis-in-a-nutshell/32.Pharma response to Ukraine war https:/ Digital Health Systems https:/ |21About the authorsSARAH RICKWOODVice President,E

179、MEA Marketing and Thought Leadership,IQVIASarah Rickwood has 30 years experience as a consultant to the pharmaceutical industry.She has an extremely wide experience of international pharmaceutical industry issues,consulting to the worlds leading pharmaceutical companies on global issues.She has been

180、 Vice President,European Marketing and Thought Leadership in IQVIA for 12 years.Sarah presents to hundreds of pharmaceutical industry clients every year on a range of global pharmaceutical industry issues,publishing white papers on many topics,including:uptake and impact of innovative medicines,and

181、challenges for Launch Excellence the impact of the pandemic on medicines markets and Rx launch Orphan drugs launch challenges Cell and Gene therapies commercialization challenges and opportunitySarah holds a degree in biochemistry from Oxford University.FIONA PEREIRAEngagement Manager,Brand&Integrat

182、ed Research Solutions,IQVIAFiona has over 15 years experience in delivering commercial and wet-lab research projects in the healthcare and pharmaceutical industries.Her focus in recent years has been on integrating a variety of research solutions to build global&local atlases of healthcare use.Integ

183、rating Data from primary and secondary research within healthcare and government settings to develop insights to drive healthcare policy decision making,and P4 healthcare(preventative,predictive,participatory and personalised).Fiona holds a PhD in Microfluidics for Biomolecule Analysis and an MSc He

184、alth Policy from Imperial College London(ICL).Additionally,she holds an Honorary Research Fellow position at Institute of Global Health Innovation at ICL.CAMILA ABELLA GMEZ(Intern)EMEA Thought Leadership,IQVIACamila lead this white paper project during her internship in IQVIA,which she completed as

185、part of her London Business School MBA course.Prior to her MBA,Camila worked as a Senior Consultant in Deloittes Spanish group.She is now Business Insight and Strategy Project Manager-IDRP in Janssen,Spain.AcknowledgmentsThe authors of this paper would like to acknowledge the support of the many IQV

186、IANs,pharmaceutical company executives and representatives of industry associations and other bodies for the time and expertise they gave so generously in the creation of this report.2022.All rights reserved.IQVIA is a registered trademark of IQVIA Inc.in the United States,the European Union,and various other countries.06.2022.NEMEACONTACT US