This document summarizes findings from surveys of sponsors and clinical research organizations (CROs) regarding quality in outsourced clinical trials. Key findings include: sponsors and CROs report moderate satisfaction with quality; cost pressures are a primary cause of quality issues; and proactive communication of quality expectations between sponsors and CROs is still lacking. Practices associated with higher quality and satisfaction include use of quality metrics and agreements. Risk-based approaches to monitoring and regional differences in quality were also discussed. Developing quality standards through collaboration between sponsors and CROs shows potential to improve outcomes.

1. 3rd$Annual$Execu.ve$Global$
Clinical$Trials$
Mitchell(Katz,(Ph.D.(
Execu3ve(Director,(Medical(Research(Opera3ons(
Purdue(Pharma(L.P.(
September(2012(

2. 2(
Pharma’s$Largest$Layoffs$in$2012$

3. 3(
CRO$Consolida.on$
! INC(
" Kendle(
! Theorem(
" Omnicare(
" IBAH(
! Pharmanet/i3(
" Inven3ve(Health(
! Private(Equity(
" PPD(
" RPS(
" PRA(

4. 4(
Outsourcing$Buzz$Words$
! Partnerships(
! Alliances(
! Preferred(Models(
! Hybrid(Models(
! Func3onal(Models(
! Transac3onal(Models(
! Offshoring(
! “Strategic(Rela3onships”(

5. 5(
Johnson$&$Johnson$and$ICON$
#1(–(Failure(to(ensure(proper(monitoring(of(the(clinical(
inves3ga3ons([21(CFR(312.50(and(312.56(a)(
#2(–(Failure(to(ensure(that(an(inves3ga3on(was(conducted(in(
accordance(with(the(general(inves.ga.onal$plan$and(
protocols(as(specified(in(the(IND([21(CFR(312.50](
#3(–(Failure(to(secure(inves.gator$compliance$with(the(
inves3ga3onal(plan(and(applicable(FDA(regula3ons([21(CFR(
312.56(b)](
#4(–(Failure(to(ensure(that(only(inves3gators(who(were(
qualified(by(training(and(experience(were(selected(as(
appropriate(experts(to(inves3gate(a(drug([21(CFR(212.53(a)](

6. 6(

7. 7(
It’s$All$About$.$.$.$
(
(
QUALITY$

8. 8(
Avoca$Quality$Consor.um$
(
Pharma(and(Biotech(members((to(date):(
! Alexion(Pharmaceu3cals,(Amgen,(Astellas(Pharma,(AstraZeneca,(Biogen(
Idec,(BristoldMyers(Squibb,(Cerexa,(Cubist(Pharmaceu3cals,(Daiichi(
Sankyo,(Eli(Lilly(and(Company,(GlaxoSmithKline,(Grünenthal,(ImClone(
Systems,(Janssen(Research(&(Development,(Otsuka,(Pfizer,(Purdue,(and(
Roche(
CRO(members((to(date):(
! Chiltern(Interna3onal,(Covance,(INC(Research,(ICON,(Harrison(Clinical(
Research,(PAREXEL(Interna3onal,(PharmaNet/i3,(PRA(Interna3onal,(
Quin3les,(Theorem(Clinical(Research,(and(RPS(
(
Corporate(Sponsors:(

9. Quality$Management$and$CRO$
Oversight$

10. 10(
Agenda$
! Overview:(Background(and(context(
! Part$1:(Overall(percep3ons(and(the(
“disconnects”(between(sponsors(and(CROs(
around(issues(of(quality(
! Part$2:(Root(causes(of(quality(issues(and(the(
issue(of(“micromanagement”(
! Part$3:(Best(prac3ce(approaches(associated(
with(sa3sfac3on(
! Open(discussion(

11. 11(
Context$for$Research$on$Quality$and$
CRO$Oversight$
! Increase(in(clinical(outsourcing(
! Consolida3on(of(spend(with(few(clinical(service(providers(
! Globaliza3on(of(clinical(trials:(increase(in(number(of(studies(in(lessdexperienced(developing(
regions(
! Focus(on(efficiencies(and(cost(savings(
! Increase(in(the(number(of(highdprofile(FDA(warning(lemers(
Focus(on(Avoca’s(2011(Industry(Survey:(percep3ons(from(sponsors(and(CROs(on(the(quality(of(
outsourced(trials(
Focus(of(Avoca’s(Quality(Consor3um:(proac3ve(quality(management(
The$focus$and$vision$of$the$Quality$Consor5um$are$to$accelerate$the$development$of$an$industry$
standard$and$best9prac5ce$approach$to$the$quality$management$of$outsourced$trials$through$the$
sharing$of$best$prac5ces$

12. 12(
Methods$
! Surveys(explored(respondents’(views(and(experiences(regarding:(
" Sa3sfac3on(with(quality(of(work(delivered(by(clinical(service(providers(
" Approaches(to(managing(quality(in(outsourced(clinical(trials,(including(
quality(metrics,(repor3ng(tools,(and(desktop(analy3cs(
" Scope(and(u3lity(of(Quality(Agreements(
" Other(tools(used(to(set(expecta3ons(for(quality(in(outsourced(clinical(
trials(
" Quality(concerns(and(management(when(outsourcing(in(Emerging(
Markets(
" Quality(considera3ons(in(selec3ng(CROs(

13. 13(
2011$Industry$Survey$
! 104(sponsor(surveys(from(66(
companies(
" 73%(pharma,(
17%(biotech(
" 52%(“Top(20”(
" 44%(Opera3ons,(
40%(Outsourcing(
" 17%(execu3ves,(
58%(middle(management((
! 143(provider(surveys(from(88(
companies(
" 78%(CROs(
" 64%(“Top(20”(
" 38%(Opera3ons,(
31%(BD,(
22%(Management(
" 48%(execu3ves,(
39%(middle(management((
247(Surveys(

14. 14(
Quality$Consor.um$Assessment$
! 428(sponsor(surveys(were(deployed(resul3ng(in(feedback(from(334(
individuals(
" Overall(response(rate:(78%(
" Completed(surveys/company:(10d46((note(that(there(was(no(associa3on(
between(company(size(and(number(of(respondents)(
" Range(of(response(rates/company:(50%d100%(
! 298(CRO(surveys(were(deployed(resul3ng(in(feedback(from(207(individuals(
" Overall(response(rate:(69%(
" Completed(surveys/company:(4d59((note(that(there(was(no(associa3on(
between(company(size(and(number(of(respondents)(
" Range(of(response(rates/company:(27%d100%(

15. Part$1:$$Framing$the$Quality$Issue$
Overall(percep3ons(and(the(
“disconnects”(between(sponsors(and(
CROs(around(issues(of(quality(

16. 16(
Methods$
! “Quality”(was(defined(as(“The$ability$to$effec.vely$and$efficiently$answer$
the$intended$ques.on$about$the$benefits$and$risks$of$a$medical$product$
or$procedure$while$assuring$pa.ent$safety$and$protec.on$of$human$
subjects”$
! As(examples,(elements(of(a(quality(clinical(study(were(said(to(include,(but(
not(limited(to:(
" Scien3fically(valid(and(ethically(sound(experimental(design(
" Adequate(protec3on(of(subjects’(rights,(safety(and(welfare(
" Qualified(personnel(
" Adequate(monitoring(
" Current,(complete,(and(accurate(data(
" Accurate(presenta3on(and(interpreta3on(of(data(

17. 17(
Industry$Survey$Sponsors:$Overall$
Sa.sfac.on$

18. 18(
Consor.um$Sponsors:$Sa.sfac.on$
with$Quality$

19. 19(
Consor.um$Sponsors:$Comparison$of$
CRO$Quality$to$Sponsor$Internal$
Teams$

20. 20(
Sa.sfac.on$with$Quality$

21. 21(
Industry$Survey:$Provider$Sa.sfac.on$

22. 22(
Sponsors:$Sa.sfac.on$with$Quality$
Areas(with(rela3vely(high(sa3sfac3on(included:(
! Compliance(with(SOPs(and(other(wrimen(procedures(
! Data$quality$and$integrity$
! Audit(plans(and(execu3on(
Areas(with(rela3vely(high(dissa3sfac3on(included:(
! Oversight(of(third(party(vendors(
! Governance(of(quality(
! Communica3ons(surrounding(quality(
! Availability(of(quality(personnel(for(projects(
! Efficiency/.meliness$in$achieving$clean$data$
! Adherence(to(monitoring(plan(

23. Part$2:$$Causes$of$Quality$Issues$

24. 24(
Causes$of$Issues$with$Quality$
“CROs,$as$service$providers,$are$heavily$incented$to$
deliver$and$measure$quality$–$and$are$prepared$to$do$
so.$$Too$many$sponsors$are$not$prepared$to$do$their$
part$in$assuring$a$rela5onship$focused$on$quality.$$So$
CROs$are$forced$to$implement$one$model$for$sponsors$
ready$to$focus$on$quality,$and$another$for$the$many$
focused$on$ac5vi5es$and$unit9level$cost.”$
( ( (d(Quota3on(from(an(Industry(Survey(Provider(Respondent(
(
(

25. 25(
Causes$of$Issues$with$Quality:$Sponsor$
Consor.um$Data$

26. 26(
Industry$Survey:$Causes$of$Issues$with$
Quality$

27. 27(
Quality$vs.$Costs$

28. 28(
Causes$of$Issues$with$Quality$
#1:$Cost$Pressures$
“The$focus$on$price$has$driven$out$the$reality$of$adequate$
monitoring$and$proper$Quality$Control$processes$to$ensure$quality$
at$the$site$level…$Too$many$procurement$officers$are$making$
decisions$purely$on$cost$without$regards$to$quality$product.”$
“Price$pressures,$especially$discounts…have$caused$some$CROs$to$
cut$corners$and$send$work$to$low$cost$regions$without$adequately$
trained$staff.”$
“Price$reduc5ons$required$to$‘play$the$game’$in$the$preferred$
provider$selec5on$process$make$it$very$difficult$to$con5nue$to$
resource$adequately.$$Sponsors$say$they$will$streamline$processes$
going$forward$to$reduce$workload$but$hardly$ever$do.”$

29. 29(
Causes$of$Issues$with$Quality$
#2:(Sponsors(DecisiondMaking(with(
Impacts(on(Quality((without(provider(
input)(
! Oversight((level(of(monitoring)(
! Protocol(design(
! Inves3gators(&(regions(
! Timelines(
! Processes(
! Thirddparty(vendors(
“It$is$difficult$to$ensure$quality$for$a$func5onal$provider$for$monitoring,$when$
the$protocol$design/site$selec5on$are$done$by$another$CRO/sponsor.”$
“There$is$a$percentage$of$work$that$we$perform$that$is$working$with$the$
sponsor$processes,$etc…in$these$circumstances,$quality,$5meliness,$training,$
governance$and$oversight$are$dictated$by$sponsor$requirements.”$

30. 30(
Causes$of$Issues$with$Quality$
#3:$Sponsor$Failure$to$Proac.vely$Make$Decisions$or$
Communicate$with$Providers$about$Quality$Expecta.ons$
Industry(survey(data:(
! Only(55%(of(sponsors(are(sa3sfied(with(their(companies’(iden3fica3on(of(process/
deliverables(for(which(quality(expecta3ons(of(CROs(need(to(be(set.(
! Only(58%(feel(that(their(companies(effec3vely(communicate(quality(expecta3ons(
to(CROs(
! Strong(associa3on(between(“proac3ve”(management(of(quality(and(ability(to(
forego(micromanagement.(

31. Part$3:$$Results$
What(can(be(done(to(enhance(quality(while(
reducing(micromanagement?(
What$quality$prac.ces$are$associated$with$
enhanced$sa.sfac.on?$

32. 32(
Industry$Survey$Sponsors:$Quality$
Metrics$

33. 33(
Consor.um$Survey:$Quality$Metrics$

34. 34(
Quality$Agreements$

35. 35(
Industry$Survey$Sponsors:$Quality$
Agreements$

36. 36(
Industry$Survey$Sponsors:$Quality$
Agreements$

37. 37(
Other$Prac.ces$Impac.ng$Quality$
Risk$Based$Approaches$
! 57%(of(sponsors(and(58%(of(CROs(use(a(formal,(riskdbased(
approach(to(levels(of(site(monitoring((industry(survey(data)(
" About(2/3(have(had(primarily(posi3ve(experiences(–(1/3(mixed(
! Most(sponsors((67%)(and(CROs((79%)(do(maintain(
documenta3on(of(site(performance(on(previous(trials(to(
factors(into(such(models.(
" Performance(data(most(commonly(includes(number(of(protocol(
viola3ons,(number(of(queries,(type(and(severity(of(protocol(
viola3ons,(promptness(of(data(entry,(types(of(queries,(and(3me(
to(resolu3on(of(queries.(

38. 38(
Quality$by$Region$

39. 39(
Summary$
! While(developing(standards(and(more(
efficient(ways(for(sponsors(and(CROs(to(work(
together(is(necessary,(it(has(been(
challenging.(
! There(is(greater(poten3al(for(success(in(
terms(of(the(ability(to(quickly(move(towards(
standards:(
( ( (Quality(Agreements(
( ( (Quality(Metrics(
! There(is(no(onedsize(fits(all(CRO(model(

40. Open$Discussion$
(
Thank(You(