Pharmaceutical Compliance Pharmaceutical Compliance Current Trends:Current Trends:

Hot Button Issues to Look at this Year Hot Button Issues to Look at this Year in Sales, Marketing, Clinical, Medical in Sales, Marketing, Clinical, Medical

Affairs and Government PricingAffairs and Government Pricing

Clinical & Medical Affairs: The Clinical & Medical Affairs: The Current Trends and Hot IssuesCurrent Trends and Hot Issues

Mark A. DeWyngaert, MBA, Ph.D.Managing DirectorHuron Consulting Group

Craig A. Metz, Ph.D.Vice President US Regulatory AffairsGlaxoSmithKline

Clinical & Medical Affairs: The Clinical & Medical Affairs: The Current Trends and Hot IssuesCurrent Trends and Hot Issues

Clinical Trial Transparency (CTR)Clinical Trial Transparency (CTR)Post Marketing Clinical Trial Post Marketing Clinical Trial CommitmentsCommitmentsIRB ConsiderationsIRB ConsiderationsInvestigator Initiated TrialsInvestigator Initiated TrialsFair Market value Fair Market value Medical Liaisons Role Medical Liaisons Role

Mark A. DeWyngaert, MBA, Ph.D.Managing DirectorHuron Consulting Group

Craig A. Metz, Ph.D.Vice President Clinical AffairsGlaxoSmithKline

Clinical Research Clinical Research TransparencyTransparency

Guiding Principles forGuiding Principles forClinical Research TransparencyClinical Research TransparencyInform the medical and academic research Inform the medical and academic research community of ongoing research and the community of ongoing research and the opportunity to participateopportunity to participate–– Prevent unnecessary study duplicationPrevent unnecessary study duplication–– Promote collaboration with industryPromote collaboration with industry

Provide information on active studies to Provide information on active studies to prospective study subjectsprospective study subjectsProvide a reference point for monitoring study Provide a reference point for monitoring study result postingresult postingProvide public access to study results (free)Provide public access to study results (free)

Clinical Study Results DatabasesClinical Study Results DatabasesProgress to DateProgress to Date

PhRMA (PhRMA (clinicalstudyresults.orgclinicalstudyresults.org) ) –– Nov 04 Nov 04 –– 174 drugs posted by 33 companies (Sept. 05)174 drugs posted by 33 companies (Sept. 05)–– 252 drugs posted by XX companies (Jan 06)252 drugs posted by XX companies (Jan 06)Astra Zeneca (Astra Zeneca (astrazenecaclinicaltrials.comastrazenecaclinicaltrials.com))–– 188 studies/29 products (Mar 06) 188 studies/29 products (Mar 06) Roche (Roche (rocheroche--trials.comtrials.com) ) –– April 2005April 2005–– 312 studies/39 products (Mar 06)312 studies/39 products (Mar 06)

Clinical Study Results DatabasesClinical Study Results DatabasesProgress to DateProgress to Date

Novartis (Novartis (novartisclinicaltrials.comnovartisclinicaltrials.com))–– 41 studies (Mar 06)41 studies (Mar 06)

Lilly (Lilly (lillytrials.comlillytrials.com) ) –– Dec 04Dec 04–– Results from 126 studies posted (Jan 06) Results from 126 studies posted (Jan 06)

GSK (GSK (ctr.gsk.co.ukctr.gsk.co.uk) ) –– Sept 04Sept 04–– Results from >2600 studies/36 products (Jun 06)Results from >2600 studies/36 products (Jun 06)

Post Marketing Post Marketing CommitmentsCommitments

The FDA and Drug Safety:The FDA and Drug Safety:A Proposal for Sweeping Changes*A Proposal for Sweeping Changes*

““According to the most recent report, According to the most recent report, there were 1231 as yet unsatisfied there were 1231 as yet unsatisfied commitments through September 2005.commitments through September 2005.””

2/3rds (797) were 2/3rds (797) were ““pendingpending”” ((ieie. not initiated). not initiated)21% were 21% were ““ongoingongoing”” or or ““delayeddelayed””Many pending study commitments lacked any Many pending study commitments lacked any deadline for completiondeadline for completion

**FurbergFurberg CD, Levin AA, Gross PA, et al. Arch Intern Med. CD, Levin AA, Gross PA, et al. Arch Intern Med. 2006; 166: 19382006; 166: 1938--19421942

Get your facts firstGet your facts first…………....then you can distort them as much as then you can distort them as much as

you please.you please.

Mark Twain Mark Twain

Tracking Phase IV Commitments at Tracking Phase IV Commitments at thethe FDAFDA

Annual reporting requirement (PDUFA 1997)Annual reporting requirement (PDUFA 1997)–– Feb 06 Final Guidance (April 2001 draft) Feb 06 Final Guidance (April 2001 draft)

(www.fda.gov/cder/guidance/5569fnl.htm)(www.fda.gov/cder/guidance/5569fnl.htm)–– Public website (Public website (www.fda.gov/cder/pmcwww.fda.gov/cder/pmc))

Annual status reports (506B) required for:Annual status reports (506B) required for:-- Studies that were a condition of Accelerated Studies that were a condition of Accelerated

ApprovalApproval-- Studies in pediatric patients required under Studies in pediatric patients required under

PREA PREA -- Studies the sponsor committed in writing to Studies the sponsor committed in writing to

conduct conduct Annual reports required until FDA provides written Annual reports required until FDA provides written notification that the commitment has been met or notification that the commitment has been met or the study is no longer feasible or the study would the study is no longer feasible or the study would no longer be usefulno longer be useful

Tracking Phase IV Commitments at Tracking Phase IV Commitments at thethe FDAFDA

ProcessesProcessesDevelop/agree study schedule/completion Develop/agree study schedule/completion datesdatesCommunicate/agree timeline revisions Communicate/agree timeline revisions –– Original timeline remains in place for Original timeline remains in place for

trackingtrackingFinal reports submitted as Final reports submitted as –– PostmarketingPostmarketingStudy Commitment Study Commitment –– Final Study ReportFinal Study Report–– FDA reviews and communicates whether FDA reviews and communicates whether

commitment has been fulfilledcommitment has been fulfilledReviews Reviews ““generallygenerally”” within 3 mowithin 3 mo

Tracking Phase IV Commitments at Tracking Phase IV Commitments at thethe FDAFDA

Commitment Status Categories*Commitment Status Categories*1.1. Pending Pending –– study has not been initiated, date for study has not been initiated, date for

initiation of enrollment has not passedinitiation of enrollment has not passed2.2. Ongoing Ongoing –– study proceeding to study proceeding to original original

scheduleschedule3.3. Delayed Delayed –– study is behind study is behind originaloriginal scheduleschedule4.4. Terminated Terminated –– study terminated before study terminated before

completion, study report not yet submittedcompletion, study report not yet submitted5.5. Submitted Submitted –– study concluded/terminated, study concluded/terminated,

notification from FDA pendingnotification from FDA pending* Where multiple studies exist for a single * Where multiple studies exist for a single

commitment, tracking is driven by the least commitment, tracking is driven by the least progressed studyprogressed study

IRB ConsiderationsIRB Considerations

Clinical Research in Clinical Research in thethe

Developing WorldDeveloping World

Key Focal PointsKey Focal Points

Data Data GeneralizabilityGeneralizabilityEthicsEthicsLogisticsLogisticsMonitoringMonitoringMetricsMetrics

Data Data GeneralizabilityGeneralizability

Potential for unknown/poorly understood regional Potential for unknown/poorly understood regional differences in medical practices/standard of caredifferences in medical practices/standard of carePotential impact of culture/language on the Potential impact of culture/language on the effective deployment of effective deployment of PROsPROs in developing in developing countriescountriesPlacebo response rates may be higher at these Placebo response rates may be higher at these sites for certain disease settings which could sites for certain disease settings which could decrease study power and lead to failed trialsdecrease study power and lead to failed trialsThe more subjective the primary registration The more subjective the primary registration endpoint is the more regulatory risk is invoked endpoint is the more regulatory risk is invoked with a VDAwith a VDA--based development programbased development program

EthicsEthics

Potential regional differences in drivers for Potential regional differences in drivers for participation in clinical trialsparticipation in clinical trials

–– Intent/ability to report adverse eventsIntent/ability to report adverse events–– Adequacy of informed consent processAdequacy of informed consent process

Need to adjust reading level/cultural contentNeed to adjust reading level/cultural content

Concerns of health/regulatory authoritiesConcerns of health/regulatory authorities““Guinea pig syndromeGuinea pig syndrome””Need to protect poor from exploitationNeed to protect poor from exploitationObtaining truly informed consent from Obtaining truly informed consent from ““unletteredunlettered””subjectssubjects

Are IRB/Ethics committees appropriately Are IRB/Ethics committees appropriately constituted/functioning at developing country constituted/functioning at developing country sites?sites?

LogisticsLogistics

Evaluating the infrastructure and Evaluating the infrastructure and understanding local expectations for understanding local expectations for infrastructure building/maintenance at infrastructure building/maintenance at sitessitesDeveloping and maintaining relationships Developing and maintaining relationships with PIs and site staffwith PIs and site staffUse of electronic data transferUse of electronic data transfer–– Data security issuesData security issues

MonitoringMonitoring

Availability of funding/staffing to conduct Availability of funding/staffing to conduct increased full site audits in these regionsincreased full site audits in these regionsUnderstanding the Regulatory Authority Understanding the Regulatory Authority view of data from these regionsview of data from these regionsMonitoring the approval metrics for Monitoring the approval metrics for NDA/NDA/MAAsMAAs with significant amounts of with significant amounts of data from developing countriesdata from developing countriesMonitoring the RA audit patterns/resultsMonitoring the RA audit patterns/results

MetricsMetrics

How are critical aspects of study How are critical aspects of study performance other than recruitment performance other than recruitment and cost per patient (e.g. protocol and cost per patient (e.g. protocol compliance, dropout rates, compliance, dropout rates, cost/cost/evaluableevaluable patient, data query patient, data query rates) being evaluated?rates) being evaluated?What is known about regional What is known about regional differences in study differences in study contracting/approval rates?contracting/approval rates?

A Word from the FDAA Word from the FDAJohn Jenkins, MD (Director, Office of New Drugs, CDER):John Jenkins, MD (Director, Office of New Drugs, CDER):

Jenkins, who spoke on the audienceJenkins, who spoke on the audience--submitted questions with CDER submitted questions with CDER asssociateasssociate director for medical policy Robert director for medical policy Robert Temple, said the trend has also caused FDA to have Temple, said the trend has also caused FDA to have ““concerns about the local standards of medical practice and how concerns about the local standards of medical practice and how that may influence the ability to extrapolate and interpret the that may influence the ability to extrapolate and interpret the data that are brought back for consideration for the U.S. data that are brought back for consideration for the U.S. population. There are huge resource implications for us,population. There are huge resource implications for us,”” he continued, in sending inspectors to foreign clinical trial he continued, in sending inspectors to foreign clinical trial sites. sites. ““Those people also have to work for the State Department, so logiThose people also have to work for the State Department, so logistically it gets very difficult to start sending stically it gets very difficult to start sending people to these foreign sites, yet at the same time we probably people to these foreign sites, yet at the same time we probably feel compelled more than ever to want to inspect those feel compelled more than ever to want to inspect those sites if wesites if we’’re not familiar with trials coming from those locations.re not familiar with trials coming from those locations.””

Robert Temple, MD (Director, Office of Medical Policy, Director Robert Temple, MD (Director, Office of Medical Policy, Director (acting) Office of Drug (acting) Office of Drug Evaluation 1, CDER):Evaluation 1, CDER):

Temple offered that the overseas outsourcing trend is making FDATemple offered that the overseas outsourcing trend is making FDA ““nervous.nervous.”” The agency doesnThe agency doesn’’t t ““know entirely know entirely whatwhat’’s reasonable,s reasonable,”” he admitted. he admitted. ““We all know that subset differences can emerge. They may or may We all know that subset differences can emerge. They may or may not be real. But not be real. But when a study from Serbia drives the whole study, I have to tell when a study from Serbia drives the whole study, I have to tell you it provokes some nervousness you it provokes some nervousness —— you donyou don’’t really t really know.know.””

There are reassurances that come with U.S. studies, Temple pointThere are reassurances that come with U.S. studies, Temple pointed out. ed out. ““The investigators in the U.S. sign [FDA The investigators in the U.S. sign [FDA Form] 1572 and if they do something disgraceful they will be barForm] 1572 and if they do something disgraceful they will be barred from further service, they can even go to jail. We red from further service, they can even go to jail. We dondon’’t have similar authority over people outside the U.S. and that lt have similar authority over people outside the U.S. and that lack makes me, at least, nervous. ... Where this ack makes me, at least, nervous. ... Where this comes up and is a real problem is where itcomes up and is a real problem is where it’’s an outcomes trial. How are you going to do a repeat survival ss an outcomes trial. How are you going to do a repeat survival study when it tudy when it looks pretty good?looks pretty good?””

But, Temple acknowledged, But, Temple acknowledged, ““those are not the studies you most worry about. Ithose are not the studies you most worry about. I’’m more worried about depression m more worried about depression studies. Westudies. We’’ve had some fairly stunning examples of at least one drug that lve had some fairly stunning examples of at least one drug that looked pretty good in studies in South ooked pretty good in studies in South America and Eastern Europe, and weAmerica and Eastern Europe, and we’’re finding them not replicable in Western Europe and the U.S. Were finding them not replicable in Western Europe and the U.S. We have no idea have no idea what that means. We have no reason to think anybody cheated.what that means. We have no reason to think anybody cheated.

““There are some of those and they make me nervous. That said, itThere are some of those and they make me nervous. That said, it’’s extremely common to accept data thats extremely common to accept data that’’s collected s collected from a wide variety of places in the world. Usually therefrom a wide variety of places in the world. Usually there’’s fair consistency and its fair consistency and it’’s not a particular problem. I have to s not a particular problem. I have to say wesay we’’ve not seen studies from India yet. Weve not seen studies from India yet. We’’ve seen a couple of giant Chinese studies that could very well fve seen a couple of giant Chinese studies that could very well figure in igure in favorable actions favorable actions —— but not India yet, although we all know people who are moving tbut not India yet, although we all know people who are moving there. When you talk to companies here. When you talk to companies about what they encounter, theyabout what they encounter, they’’re well aware that there are differences in delving through protre well aware that there are differences in delving through protocols that are different ocols that are different by region ...by region ...””

In addition to the inspectional resources problem, he said, therIn addition to the inspectional resources problem, he said, theree’’s a major language problem in many parts of the s a major language problem in many parts of the world world —— case report forms case report forms ““in a language most of us canin a language most of us can’’t read. Itt read. It’’s inevitable, the currents inevitable, the current’’s going there, theres going there, there’’s no s no doubt about it, but itdoubt about it, but it’’s not easy to know what to do. So we think its not easy to know what to do. So we think it’’s not a bad idea to have clearly U.S. data most of s not a bad idea to have clearly U.S. data most of the time.the time.””

Investigator Sponsored Investigator Sponsored TrialsTrials

Belmont* ReportBelmont* Report

““Practice refers to interventions that are designed solely to Practice refers to interventions that are designed solely to enhance the wellenhance the well--being of an being of an individualindividual patient or client patient or client and that have a reasonable expectation of success.and that have a reasonable expectation of success.

““ResearchResearch”” is an activity designed to test an hypothesis, is an activity designed to test an hypothesis, permit conclusions to be drawn and thereby to develop or permit conclusions to be drawn and thereby to develop or contribute to contribute to generalizablegeneralizable knowledge. knowledge.

**Belmont Report Belmont Report –– The National Commission for the Protection of Human Subjects ofThe National Commission for the Protection of Human Subjects ofBiomedical Research and Behavioral Research (1979)Biomedical Research and Behavioral Research (1979)

PhRMAPhRMA Study Conduct PrinciplesStudy Conduct Principles

Payment to clinical investigators or their Payment to clinical investigators or their institutions should be institutions should be reasonablereasonable and and based on based on work performedwork performed by the investigator and the by the investigator and the investigatorinvestigator’’s staff, s staff, not on any other not on any other considerations.considerations.–– http://www.fasthttp://www.fast--track.com/products.phptrack.com/products.php

A written contract or budgetary agreement A written contract or budgetary agreement should be in place, specifying the nature of the should be in place, specifying the nature of the research services to be provided and the basis for research services to be provided and the basis for payment for those services.payment for those services.Payments or compensation of any sort should not Payments or compensation of any sort should not be tied to the outcome of clinical trials.be tied to the outcome of clinical trials.Clinical investigators or their immediate family Clinical investigators or their immediate family should not have a direct ownership interest in the should not have a direct ownership interest in the specific pharmaceutical product being studied.specific pharmaceutical product being studied.

Fair Market ValueFair Market Value

The Regulatory EnvironmentThe Regulatory EnvironmentRegulatory bodies are increasingly scrutinizing payments made byRegulatory bodies are increasingly scrutinizing payments made by Medical Medical Device, Pharmaceutical and Biotechnology Companies to healthcareDevice, Pharmaceutical and Biotechnology Companies to healthcareprofessionals:professionals:–– Centers for Medicare and Medicaid Services;Centers for Medicare and Medicaid Services;–– HHS Office of Inspector General;HHS Office of Inspector General;–– Department of Justice;Department of Justice;–– State Attorneys General.State Attorneys General.

Key risk areas:Key risk areas:–– Are these payments potential inducements for product selection?Are these payments potential inducements for product selection?–– Could these payments be construed as a Could these payments be construed as a ““kickbackkickback”” or part of a or part of a ““quid quid

pro quopro quo”” arrangement? arrangement? –– Did these payments potentially initiate use of the product Did these payments potentially initiate use of the product

inappropriately?inappropriately?Risk management for Pharmaceutical Companies:Risk management for Pharmaceutical Companies:–– Demonstrate that the payments are for Demonstrate that the payments are for ““bona fide purposesbona fide purposes””..–– Demonstrate that the payments represent Demonstrate that the payments represent ““fair market valuefair market value””..

PPNPS PPNPS –– 5 Critical Elements to 5 Critical Elements to DocumentationDocumentation

Process Process –– Is there a formal process through which payment levels are deterIs there a formal process through which payment levels are determined through premined through pre--specified specified

criteria?criteria?

–– Are the payments preAre the payments pre--set and defined or can they be variable?set and defined or can they be variable?

PurposePurpose–– Why is the payment necessary?Why is the payment necessary?–– What is the underlying purpose?What is the underlying purpose?–– Is the payment potentially duplicative? Is the payment potentially duplicative? –– Is there a potential for fraud, waste, and abuse?Is there a potential for fraud, waste, and abuse?

NeedNeed–– Why is the service necessary from this individual or company?Why is the service necessary from this individual or company?–– How does it relate to the companyHow does it relate to the company’’s commercial or clinical strategy?s commercial or clinical strategy?

PaymentPayment–– Was there a determination process to derive a Was there a determination process to derive a ““fair market valuefair market value”” range for the payment?range for the payment?–– Is there a process to track the Is there a process to track the ““totality of spendtotality of spend”” on a particular healthcare professional? on a particular healthcare professional?

ServiceService–– Was the service actually performed?Was the service actually performed?–– Was there a demonstrable outcome that resulted from the payment?Was there a demonstrable outcome that resulted from the payment?

Medical Science Medical Science LiaisonsLiaisons

MSL BasicsMSL BasicsThe role of a medical science liaison is to provide scientific The role of a medical science liaison is to provide scientific and educational information to health care professionals and educational information to health care professionals ((““HCPsHCPs””))MSLs occupy a middle ground between two groups:MSLs occupy a middle ground between two groups:–– Sales and marketing Sales and marketing –– Medical communications / Medical affairsMedical communications / Medical affairs

The Food & Drug Administration (The Food & Drug Administration (““FDAFDA””) does not recognize ) does not recognize MSLs as a special classMSLs as a special class–– If MSLs sell or promote products, they are subject to the same If MSLs sell or promote products, they are subject to the same

rules as sales representativesrules as sales representativesDOJ and OIG monitor the role of DOJ and OIG monitor the role of MSLsMSLs in terms of both in terms of both healthcare compliance and offhealthcare compliance and off--label saleslabel sales

Enforcement is based on the message, Enforcement is based on the message, not the messengernot the messenger

Current MSL IssuesCurrent MSL Issues““Proactive versus ReactiveProactive versus Reactive”” behaviorsbehaviorsDefinition of Key Opinion Leader (KOL)Definition of Key Opinion Leader (KOL)IIS processIIS process-- criteria for selection and role of MSLscriteria for selection and role of MSLsInteractions with sales and marketing employeesInteractions with sales and marketing employeesConsistency in offConsistency in off--label medical information communication label medical information communication processes and messageprocesses and messageStandards for the preparation, review and approval of Standards for the preparation, review and approval of written medical information written medical information Qualifications of MSLs, job descriptions and how they are Qualifications of MSLs, job descriptions and how they are supervised supervised Verification and centralized documentation of all requests Verification and centralized documentation of all requests and responses and responses Metrics and reward system for MSLsMetrics and reward system for MSLsMonitoring/Auditing process and followMonitoring/Auditing process and follow--upup

Recent Focus on Recent Focus on OffOff--Label PromotionLabel Promotion

Federal prosecutors are increasingly focusing on Federal prosecutors are increasingly focusing on offoff--label promotionlabel promotionRed flags include:Red flags include:–– Using MSLs as a means to promote offUsing MSLs as a means to promote off--labellabel–– Targeting physicians who, because of their specialty, are Targeting physicians who, because of their specialty, are

unlikely to prescribe a drug for its approved useunlikely to prescribe a drug for its approved use–– Paying KOLs high fees to speak on offPaying KOLs high fees to speak on off--label uses or act label uses or act

as consultantsas consultants

Corporate Integrity AgreementsCorporate Integrity Agreements–– Often required as part of the settlement of federal Often required as part of the settlement of federal

investigations arising under the False Claims Actinvestigations arising under the False Claims Act–– Increased emphasis on Increased emphasis on MSLsMSLs and Medical and Medical

Communications Communications

Enforcement: Clinical Trial ResultsEnforcement: Clinical Trial Results

Federal Government has expressed Federal Government has expressed interest in this area as wellinterest in this area as well–– ““I think the focus, from our perspective is not I think the focus, from our perspective is not

just what is the impact on reimbursement but just what is the impact on reimbursement but what is the impact on patients.what is the impact on patients.””——Associate Associate U.S. Attorney James Sheehan, Eastern District U.S. Attorney James Sheehan, Eastern District of Pennsylvania (of Pennsylvania (Rx Compliance ReportRx Compliance Report, April , April 10, 2006) 10, 2006)

–– ““If I had to forecast an area that I think is If I had to forecast an area that I think is going to be a growth area it is that area of the going to be a growth area it is that area of the research that supports the clinical trials.research that supports the clinical trials.””——Sheehan, Sheehan, id.id.

Questions?Questions?

A Word from the FDAA Word from the FDAJohn Jenkins, MD (Director, Office of New Drugs, CDER):John Jenkins, MD (Director, Office of New Drugs, CDER):

Jenkins, who spoke on the audienceJenkins, who spoke on the audience--submitted questions with CDER submitted questions with CDER asssociateasssociate director for director for medical policy Robert Temple, said the trend has also caused FDAmedical policy Robert Temple, said the trend has also caused FDA to have to have ““concerns about concerns about the local standards of medical practice and how that may influenthe local standards of medical practice and how that may influence the ability to extrapolate ce the ability to extrapolate and interpret the data that are brought back for consideration fand interpret the data that are brought back for consideration for the U.S. population. or the U.S. population. There are huge resource implications for us,There are huge resource implications for us,”” he continued, in sending inspectors to foreign he continued, in sending inspectors to foreign clinical trial sites. clinical trial sites. ““Those people also have to work for the State Department, so logiThose people also have to work for the State Department, so logistically stically it gets very difficult to start sending people to these foreign it gets very difficult to start sending people to these foreign sites, yet at the same time we sites, yet at the same time we probably feel compelled more than ever to want to inspect those probably feel compelled more than ever to want to inspect those sites if wesites if we’’re not familiar re not familiar with trials coming from those locations.with trials coming from those locations.””

Robert Temple, MD (Director, Office of Medical Policy, Director Robert Temple, MD (Director, Office of Medical Policy, Director (acting) (acting) Office of Drug Evaluation 1, CDER):Office of Drug Evaluation 1, CDER):

Temple offered that the overseas outsourcing trend is making FDATemple offered that the overseas outsourcing trend is making FDA ““nervous.nervous.”” The agency The agency doesndoesn’’t t ““know entirely whatknow entirely what’’s reasonable,s reasonable,”” he admitted. he admitted. ““We all know that subset We all know that subset differences can emerge. They may or may not be real. But when a differences can emerge. They may or may not be real. But when a study from Serbia drives study from Serbia drives the whole study, I have to tell you it provokes some nervousnessthe whole study, I have to tell you it provokes some nervousness —— you donyou don’’t really know.t really know.””

But, Temple acknowledged, But, Temple acknowledged, ““those are not the studies you most worry about. Ithose are not the studies you most worry about. I’’m more m more worried about depression studies. Weworried about depression studies. We’’ve had some fairly stunning examples of at least one ve had some fairly stunning examples of at least one drug that looked pretty good in studies in South America and Easdrug that looked pretty good in studies in South America and Eastern Europe, and wetern Europe, and we’’re re finding them not replicable in Western Europe and the U.S. We hafinding them not replicable in Western Europe and the U.S. We have no idea what that ve no idea what that means. We have no reason to think anybody cheated.means. We have no reason to think anybody cheated.

In addition to the inspectional resources problem, he said, therIn addition to the inspectional resources problem, he said, theree’’s a major language s a major language problem in many parts of the world problem in many parts of the world —— case report forms case report forms ““in a language most of us canin a language most of us can’’t t read. Itread. It’’s inevitable, the currents inevitable, the current’’s going there, theres going there, there’’s no doubt about it, but its no doubt about it, but it’’s not easy to s not easy to know what to do. So we think itknow what to do. So we think it’’s not a bad idea to have clearly U.S. data most of the s not a bad idea to have clearly U.S. data most of the time.time.””