The State of Clinical Development - Globalization

January 11, 2011Doug Peddicord, PhDExecutive Director

ACRO

• In 2010, ACRO member companies managed nearly 2 million participants in over 11,500 clinical studies.

• In 2010, ACRO member companies conducted clinical studies in 114 countries across 6 continents.

• ACRO member companies currently employ over 72,000 people worldwide.

• ACRO members contributed to the development of all of top 20 selling drugs

• Member companies were involved in the development of 33 of 38 new drugs approved last year in the US and Europe

The Top CROs (as of 10-16-11)

Sources: Scrip

INCKendle

PharmanetI3

InVentiv Health

Major Pharma and CRO Clinical Headcount

Source: Tufts CSDD analysis

ACRO Member Company Expansion: 2010

ACRO Member Company Expansion: 2011

Increasing Global Site Dispersion

2002-2006(Mean # of Countries)

2006-2010(Mean # of Countries)

Phase I Clinical Trial

2 2

Phase II Clinical Trial

11 18

Phase III Clinical Trial

19 34

Source: Tufts CSDD analysis of Industry-Funded Trials Registered on clinicaltrials.gov

A Global Enterprise – Current and Recently Completed Trials

Source: ClinicalTrials.gov

Why Conduct Clinical Trials Around The World?

The answer is in the numbers: when searching for potential research participants (patients) and potential investigators, you can cast your net across 350 million, 700 million or 7 billion

And in new markets for new biomedical products - with the emergence of middle classes in China and India, for example, the size of the US

And in improving regulatory and health care infrastructures

And, temporarily at least, in lower costs

Globalization - Advantages

Availability of patients shortens recruitment time (numbers, numbers, numbers)

Time for cancer trials can be cut in half Availability of investigators and site personnel Broad adoption of GCP allows consistency Research quality standards are consistent

worldwide – proof of compliance is required by regulators in every major market

New markets (safety and efficacy demonstrated for multiple regulators)

Globalization - Challenges

Research infrastructure not as developed• Staff training, equipment, record and drug

storage conditions, potential power outages, problems with internet access

Region specific regulatory hurdles Social and cultural issues Differences in medical care Multiple IRBs/Ethics Committees Political instability, travel restrictions

Question: will regulators find study data acceptable?

Globalization - Concerns

Broad social justice issues – testing products for what kinds of diseases and conditions, with what level of transparency, to be made available in what ways to which people, within what kind of health care system?

Ethics – informed consent, undue inducement, vulnerable populations, language and cultural differences, etc.

Quality – in the training of investigators and sites, the conduct of the trial, regulatory oversight, the quality of the data, etc.

Scientific relevance (extrapolatability)

NBAC 2001 Report – selected recommendations

• FDA should not accept data from trials that do not meet ethics standards

• Studies should be ‘responsive’ to the health needs of the host country

• Community representatives should be involved in design and conduct of trials

• Members of control group should receive established, effective treatment whether available in-country or not

More from NBAC

• Voluntary informed consent is essential, including information regarding benefits, if any, after the study ends

• Cultural factors must be considered vis-à-vis informed consent

• “Therapeutic misconception” must be minimized• Participants should have continued access to

experimental interventions proven effective• Effective interventions should become available to

host country population

Going Beyond Business Considerations and Policy Recommendations

Let’s do some research – in 2010 ACRO undertook a study of global data quality. We gathered data from 25 multi-country phase 3 studies, with more than 63,000 participants

We were interested in determining if market maturity in various regions of the world (defined as “mature”, “developed” , and “emerging”) impacts the quality of clinical research data generated in support of FDA and EMA marketing authorization applications, as measured by data base query rates.

Comparison of Participating Sites and Subjects Across Various Regions

Demographic and Other Study Details

Number of subjects/study varied from 211 – 26,450; average = 2,612 Average number of queries/study = 54,568 Average number of queries/subject = 21 Average CRF = 114 pages and average number of parameters = 1443 Therapeutic Areas: cardiovascular (6), CNS (5), oncology/hematology (4), women’s health (2), general medicine (3), endocrine (1), over active bladder (1), anti-infective (1), gastrointestinal tract (1) and asthma (1)

Summary of Findings

Overall, given the large number of trials, subjects, sites and therapeutic areas included in the analyses, this study represents an attempt at unbiased evaluation of clinical trials data conducted in regions outside mature regions (North America, Western Europe and Japan).

Primary emphasis was placed on comparing data quality (data errors) for each region against those generated for the North American Region.

Our analyses indicates that there are no statistically significant differences in the total query rates or in the number of database changes between various regions or when each region was compared to North America.

The Next Research Project: 2011-2012

Global quality at the investigator/site level, i.e., quality in the conduct of the clinical trial for multi-country projects

• Quality of human subject protections: informed consent execution; inclusion/exclusion errors

• Investigator/site training and qualifications: GCP compliance; FDA and other agency inspection and audit findings

• Performance metrics: e.g., time to first patient in; number of patients per site

Assessing Global Quality at the Investigator/Site Level

Purpose: Gather data from ACRO member managed multi-regional clinical trial programs to assess:1) ‘quality’ of human subject protections; 2) investigator/site training and other qualifications; 3) site/investigator performance metrics

Status: Data gathering complete; analysis beginning

Null Hypothesis: investigator/site quality does not differ significantly between ‘mature’ and ‘non-mature’ countries.

Aligning The Incentives

Protection of subjects, adherence to GCPs = valid, reliable data

Good data (good science) = prompt regulatory review

Prompt regulatory review = increased approvals for new biomedical products, benefiting all stakeholders

Thank You!

Doug Peddicord, PhD

Executive Director

dpeddicord@acrohealth.org

www.acrohealth.org