On October 23rd, 2014, we updated our
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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 INC Kendle Pharmanet I3 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 Source: Tufts CSDD analysis of Industry-Funded Trials Registered on clinicaltrials.gov 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
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
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