Pharmaceutical Compliance Pharmaceutical Compliance Current Trends:Current Trends:

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

CommitmentsCommitments IRB ConsiderationsIRB Considerations Investigator Initiated TrialsInvestigator Initiated Trials Fair 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 Transparency

Inform 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 subjects

Provide a reference point for monitoring study Provide a reference point for monitoring study result postingresult posting

Provide 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 (roche-trials.comroche-trials.com) – April 2005) – April 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 04) – Dec 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 04) – Sept 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 “pending” (ie. not initiated)2/3rds (797) were “pending” (ie. not initiated) 21% were “ongoing” or “delayed”21% were “ongoing” or “delayed” Many pending study commitments lacked any Many pending study commitments lacked any

deadline for completiondeadline for completion

*Furberg CD, Levin AA, Gross PA, et al. Arch Intern Med. *Furberg CD, Levin AA, Gross PA, et al. Arch Intern Med. 2006; 166: 1938-19422006; 166: 1938-1942

Get your facts first……..Get 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 FDA FDA

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 PREA Studies in pediatric patients required under 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 no the study is no longer feasible or the study would no longer be usefullonger be useful

Tracking Phase IV Commitments at Tracking Phase IV Commitments at thethe FDA FDA

ProcessesProcesses Develop/agree study schedule/completion Develop/agree study schedule/completion

datesdates Communicate/agree timeline revisions Communicate/agree timeline revisions

– Original timeline remains in place for Original timeline remains in place for trackingtracking

Final reports submitted as – Final reports submitted as – Postmarketing Postmarketing Study Commitment – Final Study ReportStudy Commitment – Final Study Report– FDA reviews and communicates whether FDA reviews and communicates whether

commitment has been fulfilledcommitment has been fulfilled Reviews “generally” within 3 moReviews “generally” within 3 mo

Tracking Phase IV Commitments at Tracking Phase IV Commitments at thethe FDA FDA

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

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

scheduleschedule3.3. Delayed – study is behind Delayed – study is behind originaloriginal schedule schedule4.4. Terminated – study terminated before Terminated – study terminated before

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

Data GeneralizabilityData Generalizability

Potential for unknown/poorly understood regional Potential for unknown/poorly understood regional

differences in medical practices/standard of caredifferences in medical practices/standard of care Potential impact of culture/language on the Potential impact of culture/language on the

effective deployment of PROs in developing effective deployment of PROs in developing countriescountries

Placebo 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 trials

The 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 VDA-based development programwith a VDA-based 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 syndrome”Guinea pig syndrome” Need to protect poor from exploitationNeed to protect poor from exploitation Obtaining truly informed consent from “unlettered” Obtaining truly informed consent from “unlettered”

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 sitessites

Developing and maintaining relationships Developing and maintaining relationships with PIs and site staffwith PIs and site staff

Use 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 regions

Understanding the Regulatory Authority Understanding the Regulatory Authority view of data from these regionsview of data from these regions

Monitoring the approval metrics for Monitoring the approval metrics for NDA/MAAs with significant amounts of data NDA/MAAs with significant amounts of data from developing countriesfrom developing countries

Monitoring 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/evaluable patient, data query cost/evaluable 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 FDA John Jenkins, MD (Director, Office of New Drugs, CDER):John Jenkins, MD (Director, Office of New Drugs, CDER):  

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

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

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

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

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

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

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

““Research” is an activity designed to test an hypothesis, Research” 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 – The National Commission for the Protection of Human Subjects of Belmont Report – The National Commission for the Protection of Human Subjects of Biomedical Research and Behavioral Research (1979)Biomedical Research and Behavioral Research (1979)

PhRMA Study Conduct PrinciplesPhRMA Study 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 investigator’s staff, investigator’s staff, not on any other not on any other considerations.considerations.– http://www.fast-track.com/products.phphttp://www.fast-track.com/products.php

A written contract or budgetary agreement should A written contract or budgetary agreement should be in place, specifying the nature of the research be in place, specifying the nature of the research services to be provided and the basis for payment services to be provided and the basis for payment for those services.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 Environment Regulatory bodies are increasingly scrutinizing payments made by Medical Regulatory bodies are increasingly scrutinizing payments made by Medical

Device, Pharmaceutical and Biotechnology Companies to healthcare Device, Pharmaceutical and Biotechnology Companies to healthcare professionals: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 “kickback” or part of a “quid Could these payments be construed as a “kickback” or part of a “quid

pro quo” arrangement? pro quo” 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 “bona fide purposes”.Demonstrate that the payments are for “bona fide purposes”.– Demonstrate that the payments represent “fair market value”.Demonstrate that the payments represent “fair market value”.

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

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

criteria?criteria?

– Are the payments pre-set and defined or can they be variable?Are the payments pre-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 company’s commercial or clinical strategy?How does it relate to the company’s commercial or clinical strategy?

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

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 (“FDA”) does not recognize The Food & Drug Administration (“FDA”) 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 representatives DOJ and OIG monitor the role of MSLs in terms of both DOJ and OIG monitor the role of MSLs in terms of both

healthcare compliance and off-label saleshealthcare compliance and off-label 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 Reactive” behaviorsProactive versus Reactive” behaviors Definition of Key Opinion Leader (KOL)Definition of Key Opinion Leader (KOL) IIS process- criteria for selection and role of MSLsIIS process- criteria for selection and role of MSLs Interactions with sales and marketing employeesInteractions with sales and marketing employees Consistency in off-label medical information communication Consistency in off-label medical information communication

processes and messageprocesses and message Standards 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 MSLs Monitoring/Auditing process and follow-upMonitoring/Auditing process and follow-up

Recent Focus on Recent Focus on Off-Label PromotionOff-Label Promotion

Federal prosecutors are increasingly focusing on Federal prosecutors are increasingly focusing on off-label promotionoff-label promotion

Red flags include:Red flags include:– Using MSLs as a means to promote off-labelUsing MSLs as a means to promote off-label– 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 off-label uses or act Paying KOLs high fees to speak on off-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 MSLs and Medical Increased emphasis on MSLs 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.”—Associate what is the impact on patients.”—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 going If I had to forecast an area that I think is going to be a growth area it is that area of the 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 FDA John Jenkins, MD (Director, Office of New Drugs, CDER):John Jenkins, MD (Director, Office of New Drugs, CDER):  

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

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

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

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

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