3rd$Annual$Execu.ve$Global$Clinical$Trials$

Mitchell(Katz,(Ph.D.(Execu3ve(Director,(Medical(Research(Opera3ons(

Purdue(Pharma(L.P.(

September(2012(

2(

Pharma’s$Largest$Layoffs$in$2012$

3(

CRO$Consolida.on$!  INC(

"  Kendle(!  Theorem(

"  Omnicare("  IBAH(

!  Pharmanet/i3("  Inven3ve(Health(

!  Private(Equity("  PPD("  RPS("  PRA(

4(

Outsourcing$Buzz$Words$

!  Partnerships(!  Alliances(

!  Preferred(Models(

!  Hybrid(Models(

!  Func3onal(Models(

!  Transac3onal(Models(

!  Offshoring(

!  “Strategic(Rela3onships”(

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(

7(

It’s$All$About$.$.$.$

(

(

QUALITY$

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:(

Quality$Management$and$CRO$Oversight$

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(

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(

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(

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(

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%(

Part$1:$$Framing$the$Quality$Issue$

Overall(percep3ons(and(the(“disconnects”(between(sponsors(and(

CROs(around(issues(of(quality(

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(

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

18(

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

19(

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

20(

Sa.sfac.on$with$Quality$

21(

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

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(

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

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(

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

26(

Industry$Survey:$Causes$of$Issues$with$Quality$

27(

Quality$vs.$Costs$

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(

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(

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.(

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(

Industry$Survey$Sponsors:$Quality$Metrics$

33(

Consor.um$Survey:$Quality$Metrics$

34(

Quality$Agreements$

35(

Industry$Survey$Sponsors:$Quality$Agreements$

36(

Industry$Survey$Sponsors:$Quality$Agreements$

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(

Quality$by$Region$

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(

Open$Discussion$

(

Thank(You(