1. Roadmap to Emerging Regions: Clinical Trials in Developing Countries
International Clinical Trials Conference
New York, 26 February 2009
Written By:
Cristiana Spontoni
Partner
Squire, Sanders & Dempsey L.L.P.
Brussels
Presented by:
Michael A. Swit, Esq.
Vice President
The Weinberg Group Inc.
San Diego, California

2. US and EU Data on Trials in Emerging Regions

3. The Global Landscape
69,175 clinical trials are being carried out in 161 countries1
Increasingly being conducted in Central & Eastern Europe, Latin America and Asia
Majority of trials are conducted in the U.S. and Western Europe
Trials increasingly outsourced to Clinical Research Organizations

4. Globalization of Trials: European Data
According to the EMEA, around one quarter of patients recruited in pivotal trials submitted in MAAs to EMEA between 2005 and 2008 were recruited in:
Latin America
Asia
CIS
Africa

5. Recurrent Themes in Global Trials
Good central coordination but flexibility to local requirements/habits/culture (eg, CTA templates)‏
Sound use of resources: CRO, PIs, Sites: how much should be delegated and how much should be kept under control (eg, negotiating/entering CTAs, filing for regulatory approvals)‏
All the more true in emerging economies…

6. Advantages and Challenges

7. Advantages Of Emerging Economies
Limited costs: drugs, hospitalisation, travel and other general expenses, basic support services
Higher number of patients, especially naive patients (i.e., patients who never received a treatment)‏
Large patient populations with diseases of both developed and developing countries (e.g., HIV/AIDS)‏
Multi-ethnic/multiracial populations
Wide spectrum for diseases
Potential new markets (e.g., China)‏
Competent/motivated PIs

8. Clinical Trials in Emerging Regions
Conducting trials in emerging regions poses a number of challenges:
Different treatments and standard of care
Differing levels of clinical research experience and sophistication
Different capabilities of CROs in the region
Requires greater direct management efforts
Many apparent similarities in challenges requiring different responses
However, conducting trials in these regions comes does pose a number of challenges:
-Medical practice is different outside the U.S., and standards of care will differ not only as compared to the U.S. but within the country itself.
-There are differing levels
-There are different treatments and standards of care which can affect how your trisl
-Conducting trials in these regions poses a number of challenges
Different treatments and standard of care
(not only as compared to the U.S. but differing standards of care within the social structure)

9. Challenges of Conducting These Clinical Trials
Regulatory
Trial Designs
Regulatory Authorities and IRB/ECs
Translation requirements
Import/Export licenses
Legal
Contracts/Clinical Trial Agreements
Insurance requirements
Intellectual property issues
Other
CRO Partnering
Site/Investigator Identification
Adherence to Good Clinical Practice
Assuring the Ethical Conduct of the Trial
Quality Control issues
Cultural and infrastructure considerations
Do you have the appropriate trial design. Is your protocol implementable? Does it align with the medical practice in the country or region and major OECD countries which will be target.
Regulatory Authorities and IRB/Ecs
Are the regulatory laws and support in place for conducting clinical trials?
Are institutional review boards and ethics committees set up to conform to Good clinical practice standards?
What are the approval timelines and how is that going to affect the start up of your study?
What are the translation requirements for regulatory submissions and for the actual conduct of the study.
Import and export licenses
Are you going to be able to get your Study drug, Study materials, equipment, lab supplies in and out of the country in a timely manner
U.S. contracts may not be transferable to an emerging region
How the contracts going to be structure
2 way, 3 way, or 4 way contracts
Sponsor, Sponsors rep + Study institution
Sponsor + Rep + Institution + the Investigator
What are the insurance requirements in the country or region
What is the insurance underwriter going to expect from you in order to underwrite your trial
Will your intellectual property be protected in these far off countries?
Then there are the other considerations that you have to take into account
- What are the CROs like in the region?
- What is there experience and ability to provide adequate monitoring for your study
Are the investigators and site staff experienced or sophisticated enough to be able to carried out your study?
Are they experience with Good Clinical Practice
Will your trial be conducted ethically in terms of patient recruitment and safeguarding of subjects’ rights?
How will the culture affect how you design your trial, recruit sites and investigators and how your patients are recruit?
Infrastructure in place to adequately store your supplies? And if it is not what do you do about it?

10. An ordinary day in an ordinary global trial -- Some real life experiences --

11. Practical Challenge: Control of Temperature
“Control of storage and transportation temperatures is essential in maintaining the quality of medicines and in helping to protect patients from sub-standard or ineffective medicines that may result from inadequate control” (J. Taylor, Quality and Standards Manager, MHRA)‏
Increased risks for biotech products, vaccines, blood products, semi-solids, chemically unstable at certain temperatures, and of course, study drugs.

12. Let’s Get a Fridge! Sponsor wants to perform a study at site x
Site x does not have a way of keeping Study Drug at appropriate controlled temperature
Let’s get a fridge there!
OK BUT…
Can sponsor sell/donate the fridge?
To whom? Under what circumstances? Do we need a written contract? Do we need to get prior authorizations? From whom?
What if Site is a public hospital?
What if we are talking about very expensive medical devices?
Can the fridge be imported in country x?

14. Legal Challenge: Study in 21 Jurisdictions in the EMEA Region
Can a CTA be entered by a non-local Sponsor?
Answer: - Yes, BUT -- in one jurisdiction, still need to go through local entity or mediator - Yes BUT -- in Israel, sites often will object to contracting with a non-Israeli entity - Yes BUT -- certain regulatory procedures will have to be performed by local entities either because it is required by law (e.g., Ukraine) or because -- that’s the way we do things here  (Middle East)‏

15. Legal Challenge 2: What’s the Right Price?
Sponsor sells x vials of Study Drug to a non EU European country
Custom authorities google name of Study Drug and find its price in the US: 10,000 USD
Custom authorities apply a custom duty considering that value of the Study Drug
Should Sponsor pay?
What’s the practice in other countries?

16. Ethical Challenge: Unusable Data
Violations result in unusable data: in requesting marketing authorisation, a company submits a file to the EMEA, which includes the description of the trial performed. In examining the file, the EMEA evaluates the respect of GCP, the granting of informed consent and the approval by ECs.
Illustrates just how important compliance with GCP will be

17. The Emerging European Jurisdictions and Their Rules

18. The Rules in Emerging EU Jurisdictions
Estonia, Hungary, Latvia, Lithuania, Czech Republic, Slovakia, Slovenia, Poland, Bulgaria, Romania, Malta, Cyprus: now all EU countries
Directive 2001/20/EC on clinical trials applies:
- GCP standards - Uniform regulatory requirements - BUT: local challenges still remain
Highly educated and competent investigators

19. The EU Directive on Clinical Trials
Same rules (in principle!) across 27 jurisdictions
Commercial + Non-commercial trials
Phases I,II,III,IV
All trials except “non-interventional” trials

20. The Sponsor Industry, Government, Research Council, University, …
Does not need to be EU-based but must appoint EU-based representative that bears civil and criminal liability as EU-based sponsors
Sponsor can delegate (NOT transfer!) sponsor responsibilities to third parties (e.g., CROs) BUT sponsor bears ultimate responsibility

21. Protection of Trial Subjects
Informed consent
Special consideration for children and incapacitated adults
Data protection:
Directive 95/46/EC regulates strictly any processing or transfer of data outside the EU
Medical data qualifies as “sensitive”
The US is considered not a “safe place” for the purpose of data protection

22. Commencement of Trials in the EU
Sponsor applies for EUDRACT number
Application to EC
Notification to CA
CA no grounds
for
non-acceptance
Explicit
authorization
required only
in certain
cases
Favorable
Opinion of EC
60 days max 1 x clock stop for info.
days max
No Time Limit (exception)
Separate procedures
but can run in parallel
One opinion per MS

23. Conduct of a Trial – Reporting Obligations
Substantial amendments to be notified to ECs and CAs (35 days max)‏
Safety measures adopted to protect safety of subjects
Notification of trial end (90 days or 15 if early termination)‏
Notification of SUSARs
fatal or life threatening: 7 days
other SUSARs: 15 days
annual reporting
Notification of Serious Adverse Events
Guidance on reporting and standard forms

24. IMPs – Investigational Medicinal Products
Manufacture/importation authorisation
Authorisation holder must have QP at disposal: check compliance with EU GMPs or standards that are “at least equivalent”
IMPs must be supplied free of charge

25. Suspension of Trials - Infringements
CAs can suspend or prohibit trials if:
conditions for granting authorisation for trial conduct are not met anymore
doubts about safety/scientific validity
Must consult with sponsor/investigator except in cases of “imminent risk”
CA will inform other CAs, EMEA and European Commission
You may have duty to inform FDA as well

26. Inspections on GCP/GMP Compliance
Before, during or after completion of a trial
As part of marketing authorisation process or follow-up to it
At: trial sites, IMP manufacturing site, any laboratory used in the trial, or at sponsor’s premises
Conducted by CAs

27. GCP Violations = Unusable Data
Drugs reviewed by the EMEA can be granted a marketing authorization only if they are based on clinical trials conducted in compliance with the Declaration of Helsinki
In requesting marketing authorisation, a company submits a file to the EMEA, which includes the description of the trial performed. In examining the file, the EMEA evaluates the respect of GCP, the granting of informed consent and the approval by ECs.
When problems are identified, namely regarding ethical aspects, the EMEA can advise the Commission to refuse the marketing authorisation or can advise the withdrawal of marketing authorisation already delivered by Member States. This information is also made public.
However, the EMEA intervention happens after the clinical trial is finalised and presented in the file and not before or during the trial.

28. Inconsistent Approach/Interpretation
An example…
Question: can sponsor be non-EU based?
EU law answer: yes, if it appoints a EU-based representative
Answer in BG, Czech Rep., Estonia, Latvia, Lithuania, Malta, Romania, Slovakia, Slovenia: yes, if it appoints an EU representative
Answer in Cyprus: NO!

29. EU Rules on Trials Conducted in Third Countries

30. EU Rules on Trials in Third Countries
Financial penalties apply in case of failure to comply with clinical trials requirements
Sites in third countries can be inspected by the competent authorities of Member States. The EMEA has a system of GCP inspections in third countries since 2006 which has led to an increasing number of inspections in Latin America, Africa and Asia
Inspections concentrate primarily on: informed consent and appropriate EC (IRB) approvals
EU assisting on GCP capacity building/inspections a number of countries - in last EMEA GCP Inspectors’ WG workprogramme: Croatia, Macedonia, Turkey

31. Increased Regulatory Scrutiny
A European Commission paper of 2002 indicated that:
The regulatory framework for clinical trials is expected to adapt to the globalization.
the budget and number of international/national GCP inspectors is expected to increase
more information on all these clinical trials should be available through an international database
the key role of IRBs and of capacity building in this area

32. Increased Regulatory Scrutiny …
Opinion 17 of the European group on ethics in science and new technologies to the European Commission: “Ethical aspects of clinical research in developing countries” (February 2003)‏
: Series of Parliamentary Questions on trials in poor countries
On 5 December, the EMEA issued a strategy paper on: “Acceptance of clinical trials conducted in third countries for evaluation in Marketing Authorisations”

33. EMEA Action Plan: Watch This Space!
Three-year-s action plan includes:
Clarify application of ethical standards
Consider issues driving recruitment of subjects in third countries
Consider tools to respond to non-compliance/step up GCP inspections
Training of EMEA/sponsors/experts
Increased transparency: EPAR should include a clear description of the assessment of ethical standards of trials in emerging economies
Promote capacity building also through EU funding instruments

34. Wrap-Up Clear opportunities ahead of sponsors in emerging regions
Require strong central coordination and resource management
But, also must understand need for flexibility in approach and understanding of local specificities
Beware of compliance pitfalls no matter where you conduct your trial!

35. Cristiana Spontoni, Partner
Thanks!!
Cristiana Spontoni, Partner
T:   E:

36. Roadmap to Emerging Regions: Sponsor Experiences in Central Europe and Asia Carlos F. Peza February 26, 2009

37. Recent Experiences in Emerging Regions
Phase IV trial in Oncology conducted in
5 countries (France, Germany, Greece, Italy, Slovenia)
250 sites
8,448 valid subjects (3,719 valid controls)
Field period from November 2005 to October 2008
Cross-Sectional Survey on Tobacco Prevalence in Indonesia
Inclusion criteria similar to control inclusion criteria in European study
11 sites
1,500 valid subjects
Field period from January to October 2007
Research was financially supported by Philip Morris International
Cristiana asked me to speak to you about our own recent experiences as study sponsors of two studies carried in the regions of interests. That point out the differences in working in different emerging regions with different levels of sophistication.
Two contrasting trials showcasing the challenges you may face in different emerging regions.
We recently completed the field period on a case-control study carried out in 5 European countries including Slovenia.
For the study we recruited more 250 sites in France, Germany, Greece, Italy, and Slovenia
More than 8,000 subjects (60% of which were newly diagnosed lung cancer patients) over a 3 year period.
In 2007, we also carried out a cross-sectional study on smoking prevalence in Indonesia.
For this study the inclusion criteria were similar to that used in the European study
Over a 38 week period more than 1,500 valid subjects were included into the study
To add to the complication of carrying out these study, this studies were financially supported by Philip Morris International

38. Slovenia

39. Why Slovenia?
Small number of sites provided access to almost every subject in the country who was suffering from the target condition
Regulatory Agency and Central Ethics Committee are among the most efficient in Europe
Highly educated and motivated Investigators
Local CROs charged competitive fees for their services
Relatively few challenges for study start up and conduct
-Did not originally envision that Slovenia would be one of the study countries.
-However, as patient recruitment was not meeting the originally intended targets, we decided to expand the study into Slovenia
-Slovenia was very attractive to us for a number of reasons:
-It’s a small country about the size of New Jersey which meant that a small number of sites could potentially give us access to our target patients.
-We felt that there could be a quick start up given that regulatory agency and the ethics committee routinely reviewed studies and provide responses/authorization given within 60 to 90 days
-Actually most reviews are being completed within 60 days
-Highly educated health care professionals, good knowledge of English language and strong medical backgrounds
-Operating costs for CROs were 20-30% less than CROs in Western Europe.
-However, investigators in Slovenia and the rest of Central and Eastern Europe are aware of the honoraria paid in western Europe and expected to be compensated the same.
Relatively few challenges for study start up and conduct
EU Member
EU Directive on clinical trials.
There is a core set of documents required for all submissions and a common application form for both regulatory and ethics submissions

40. Specifics of Slovenian Situation
Small country, well reachable
Centralized healthcare system with developed referral network
Approximately 100 clinical trials are performed annually
Laws and regulations for conducting clinical trials are based on EU Clinical Trials Directive (2001/20/EC)
Agency for Medicinal Products and Medical Devices (JAZMP) is the competent authority for clinical trial authorization
EC approval given at the national level by the National Medical Ethics Committee
National Cancer Registry
As I said, it is small country which can be easily reached from other parts of Europe.
-Centralized healthcare system, with a strong referral network.
- Our target patients are diagnosed on the periphery
- But treated in the capital city, Ljubjlana – This was an advantage as it decreased CRO transportation costs
- About clinical trials are performed in Slovenia each year. Most of these trials are ulticentre, international clinical trials
- Laws conducting clinical trials are based on EU Clinical Trials Directive (2001/20/EC)
Drug Law and Bylaw on Clinical Trials
The code of medical deontology of Slovenia
The Ovedio Convention
- The regulatory agencies and Ethical committees are in place and considered some of the most efficient in the region.
Agency for Medicinal Products and Medical Devices (JAZMP) is the competent authority for clinical trial authorization
Authorization is required only for trials involving advanced therapy medicinal products
All other trials require only notification
Recently local research ethics committees have been set up at university and regional hospitals, but these are only authorized to review local study that do not pose any serious to the participants.
For us, there was also solid epidemiological data in place to be able to guide our patient recruitment targets
In preparing to incorporate Slovenia into an already running study, we did see a few potential issues which needed to be addressed.

41. Overcoming the Challenges in Slovenia
Challenge: Identifying and vetting the appropriate CRO
Identify the strength and weaknesses of potential vendors
Understand how you will have to supplement for the potential weaknesses
Our approach:
Vetted international and national CROs
Decided on National/Local CRO
Identified its strengths
Worked with them to shore up their potential weaknesses
The first of these issues was identifying the appropriate CRO to help us enter the region.
As you may know, different issues arise when working with international, regional or local CROs. Each has its strengths and weaknesses.
We vetted of national and international CROs and decided on a national CRO.
Our feeling was that while business culture in Slovenia is very much like that of Western Europe, you also have to keep in mind that the country as only been independent for about a quarter century.
They are a proud people and really don’t want some German or Austrian outfit coming in and telling them how to run there study.
Additionally, the benefits of working with National CRO are that they have
Better knowledge of the national environment
Understanding of the local culture
Local networks
Lower costs than a international CROs
Better flexibility
Of course, they are weaknesses as well
Limited resources
Restricted capacity to expand
Appropriate SOPs may not always be in place.
With this understanding we knew that we had to develop our budget to provide the adequate resources, training and procedures to carry out the study.

42. Overcoming the Challenges in Slovenia
Challenge: Obtaining ethics approval for a controversially funded study
Our approach:
Recruited Principal Investigator wisely
Provided him with the information needed to fully understand and promote the study
Became invested in the study
Good reputation, leadership skills, and willing to act as a key advocate of the study
Set the stage with Ethics Committee
Identified, recruited and developed good working relationship with Key Opinion Leaders in order to understand local considerations
Understood the potential concerns of the members
Addressed these during the submission
Gained support of stakeholders and who demonstrated this support to EC
Given the controversial nature of the product under study and the funder of the study, we put in a lot of thought as to how the study should be designed and presented to ethics committees.

43. Overcoming the Challenges in Slovenia
Challenge: Achieving potential subject recruitment
Our approach:
Developed Principal Investigator and sub-investigators as key promoters and coordinators
Coordination and promoting activities of different sites
Coordinating and promoting study within site
Developed investigator network where subjects were identified in the periphery and “treated” in the central location
Motivated site team
Actively recognize the role of each site member
CRA partnership with sites
Kept site team informed and involv
Centralized healthcare system with developed referral network
International IM , being part of the European science community

44. Slovenian Participation in the Study
1 Local/National CRO
16 Sites
1 Country Principal Investigator, 24 investigators/subinvestigators, more than 20 study nurses
Comparably high recruitment rate
First patient in: April 2007
1,391 valid subjects (721 valid controls)
16% of total study subjects recruited within one year
Recruitment rate stable over the year (no holiday gaps) -

45. Our Experience in Slovenia
Excellent experience in Slovenia
High subject recruitment rate
Qualified and motivated medical professionals
Uniformed regulatory issues as in Western Europe
EU Clinical Trials Directive, ICH and GCP already implemented
Relatively lower CRO costs to conduct the trial

46. Indonesia

47. Indonesian Smoking Prevalence Study
Originally intended to conduct a series of studies to understand the relative risks of smoking for a several disease end point
Planned to conduct several case-control studies for each of the disease endpoints
In planning the studies, it was determined that there did not exist valid epidemiological data to be able to guide the design of the studies
A pilot study of patients in hospitals to be used in the case-control studies was conducted
-Originally intended to conduct a series of studies to similar to the European study in order to better understand relative risks of smoking for the following disease endpoints
Lung Cancer
Respiratory Disease
Cardiovascular Disease
Our plan was to conduct several case-control studies for each of the disease endpoints
In planning the studies, it was determined that there did not exist valid epidemiological data to be able to guide the design of the studies
- In order to gather these data and determine the viability of conducting these types of studies in Indonesia, a pilot study of patients in hospitals to be used in the case-control studies was conducted

48. Specifics of the Indonesian Situation
Large Country
Very few trials being conducted, but numbers are growing.
Government and investigators receptive to industry knowledge
GCP implemented into national laws and guidelines governing clinical trials
ECs to be established at institutional, regional/provincial, and national levels according to need
National Agency for Drug and Food Control is competent authority for clinical trial authorization
Lack of population-based registries
Hospital based-cancer registries in 13 cities
About 3 times the size of Texas
230 million inhabitants, 4th largest population in the world.
Despite the strategic position among in the region as the largest populated country and the bigger pharmaceutical market, has not been so far taken up in as one of the workable and qualified medical sites among Asian countries
China, Malaysia, Singapore and Thailand have been regarded as more workable medical sites of Asian clinical trials by Japanese firms
25 trials in 2005, 31 in 2006, and 71 trials in Most are Phase III trials

49. Indonesian Smoking Prevalence Study
Cross-sectional study on the smoking prevalence of Indonesian male hospital patients
Study performed to regulated standards of a clinical trial
11 hospital sites in Jakarta, Solo, Surabaya, Padang
1 Principal Investigator, 22 investigators/subinvestigators, 60 CRA/interviewers
More than 18,000 medical records evaluated
1,533 valid subjects recruited
38 week field period

50. Overcoming the Challenges in Indonesia
Challenge: Designing a clinical trial to account for the specifics of the region
Cultural issues
Inclusion/Exclusion Criteria
Trial Length and approval timings
Infrastructure issues
Investigator and Staff Training
Our approach:
Trial designed to account:
Differences in medical practice (disease diagnosis, investigator-patient relationship)
Translation of study/regulatory documents
Validation of measurement scales (patient questionnaire)
Understood need to apply “partnership approach” to build supportive relationships

51. Overcoming the Challenges in Indonesia
Challenge: Identifying and vetting the appropriate CRO partner
No local CROs
Only a handful of Regional CROs working in Indonesia
Our approach:
Decided on one regional CRO
Worked on setting clear expectations on how the study should be conducted
Task distribution (assigning of responsibility)
Which SOPs were going to be used
Increased communication
Thorough training of CRO staff and co-monitoring visits
Only a handful of Regional CROs working in Indonesia
- We were able to identify 3 CROs
None had fixed offices in Indonesia

52. Overcoming the Challenges in Indonesia
Challenge: Investigators and Staff experience
Lack of clinical trial experience
Gaps between concept and reality in the field
Our Approach:
Incorporation of GCP, ethical practices, clinical management training into Investigator Meetings, CRA/interviewer training, monitor training
Special emphasis on informed consent process
The training methods paralleled the expected performance of the study team
Site based CRAs conducting SDVs during patient recruitment process
Increased site monitoring
- Majority of potential investigators lacked knowledge of clinical trial regulations, ethics and good clinical practice or the skills for clinical trial management
Gaps can be observed between GCP concept and reality in the field
lack of understanding of the necessity of GCP
– SAE reports (although SAEs clinically addressed)
– confidentiality
– documenting and archiving data
• dealing with clinicians – not with scientists
Additionally,

53. Overcoming the Challenges in Indonesia
Challenge: Local infrastructure and sites constraints
Lack computerized central patient database systems
Lack of secure storage space
Difficult internet and phone access
Understaffing
Our approach:
Site auditing prior to contract signature
Financial investments made into resources and personnel
Regular monitoring

54. Overcoming the Challenges in Indonesia
Challenge: Cultural Complexities
Hierarchical social structure impacts recruitment
Investigator
Site
Patient
Our approach:
Build trust and cultivate relationships
Principal Investigator
Key Opinion leaders
Involve hospital administration in site selection and start up activities
Train and inform on “foreign” practices and international expectations
Indonesia has a hierarchical social structure that affects all aspect of life and business
This affects the recruitment of sites, investigators, and patients.

55. Our Experience in Indonesia
Untapped potential
Large patient pool
Many potential sites
Government and Investigators very eager to bring more clinical research into the country
Need for capacity building
Limited infrastructure
Continued need to help local authorities adjust their regulatory environment to allow high quality clinical research

56. Approaches to Consider
Advance preparation and strategy development
Thorough knowledge of local processes and operations
Design trial with an implementable protocol
Upfront dialogue and partnership-oriented approaches
Identify a CRO that is suitable for you
Know your limitations and how much you are willing to concede to your vendors
Audit CRO, site and monitors
GCP training before start of the study
Close monitoring during the study
What is your plan B?
-There is not going to be a one size fits all trial design
-An effective trial is going to require advance preparation on your part in order to develop an adequate study.
thoroughly evaluate CROs and clinical research facilities by conducting clinical audits of vendors and clinical researchers prior to entering into contractual agreements (Note: such audits must be conducted by qualified independent auditors. Monitors should never be used as auditors as most lack sufficient training and experience and by virtue of their charge will introduce bias into the audit process)

57. Questions? Carlos F. Peza Consultant The Weinberg Group Inc.
One Embarcadero, Suite 500
San Francisco, CA P

58. About Your Speaker
Carlos Peza is a Consultant at The Weinberg Group. He recently served as Project Manager for a large international Phase IV oncology trial. The study was carried out in more than 250 sites in five European countries and enrolled more than 8,500 valid subjects. Mr. Peza also managed a cross-sectional study on smoking prevalence in Indonesia. The study field period took place over a period of 38 weeks in in 11 sites in Indonesia. More than 18,600 medical records were reviewed and valid data was collected from more than 1,500 subjects. His main tasks in these studies were interacting with international, national, and regional CROs to assure comprehensive management of the studies. In addition, he managed the development and implementation of the data collection instruments and all interview-related project components, including the development of a computerized questionnaire instrument for the European study, translation of the data collection instruments into the appropriate country languages, as well as the training and monitoring of interviewers Through his experience at The Weinberg Group, Mr. Peza has developed a significant knowledge of protocol design, questionnaire design, data collection methods, survey quality, coverage error, and interviewer effects.