Data from member companies of the US-based Association of Clinical Research Organizations (ACRO) suggest there are no significant differences in the quality of clinical trial data – as measured by query rates and database changes – when these studies are run in developing or mature regions of the world, a new study has found.
Published in the July 2012 issue of the Drug Information Journal, the statistical analysis was conducted by Pankaj Desai and colleagues from the Drug Development Graduate Program at the College of Pharmacy, University of Cincinnati in the US as well as from Cincinnati-based INC Research.
Desai is also a member of Shivani Enterprises Inc, which provides consultancy services to the Association of Clinical Research Organizations.
The researchers looked at data from 26 large phase II/III trials conducted by ACRO members in multiple regions of the world, covering 4,721 trial sites in total and involving 63,871 participants.
While the study had its drawbacks, including limited data from regions such as China and Japan, it provides an “initial indication” that data quality from developing regions such as India, Eastern Europe or Latin America is consistent with that generated in the US and Canada, noted ACRO, which said it was “very pleased, but not surprised” by the findings.
The ACRO member-company dataset included 1.39 million queries overall, spanning 7.5 million case report-form (CRF) pages and 95 million data parameters. As Desai et al point out, a query is generated when a discrepancy is observed between protocol or source data and the corresponding CRFs. Resolving these discrepancies may result in a database change.
In the analysis reported in the Drug Information Journal, the number of queries for the various regions in which multicentre studies took place was added for each trial and normalised to the number of CRF pages involved or the number of CRF data parameters. The calculated mean query rates and database-change rates were then compared using parametric and non-parametric statistical methods.
Fraught with challenges
While some emerging regions for clinical research are experiencing significant economic growth, advances in biomedical education and improvements in overall standards of living, the increased participation of these regions in clinical trials is “fraught with numerous challenges and ethical dilemmas”, the authors acknowledge.
These include widespread disparities in socio-economic and educational status, as well as in access to low-cost medication. “In many instances, the rapid growth in the private sector has occurred despite inadequate infrastructure and formidable governmental/ bureaucratic hurdles and nebulous and antiquated regulatory guidelines,” Desai et al add.
There is also in emerging markets a limited pool of well-trained clinical researchers and regulators, who are “still working to ensure the appropriate safeguards and oversight mechanisms are in place”.
These disparities have raised concerns about the quality of data generated from clinical studies conducted in developing/emerging countries relative to mature regions such as North America and Western Europe, the authors note.
“Indeed, various regulatory and governmental agencies and the public at large are apprehensive about the assimilation of data from the emerging countries for the approval of drugs in the United States and Western Europe,” they state.
Since clinical-trial data provide the basis for both internal business and external regulatory decision-making, there is “a critical need by the industry to ensure data accuracy and integrity”, Desai et al comment.
Seven globally active ACRO members supplied de-identified data on the number of queries associated with clinical trials conducted in numerous countries that could be grouped into one of 10 regions around the globe: Covance, ICON, Kendle (now part of INC Research), PharmaNet, PPD, Quintiles and RPS.
The regions and participating countries were Africa (South Africa); North America (US and Canada); Latin and South America (Argentina, Chile, Columbia, Dominican Republic, El Salvador, Guatemala, Mexico, Peru, Puerto Rico); China; the Middle East; Eastern Europe and Russia (Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Russia, Serbia, Slovakia, Slovenia); Western Europe (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland); Japan; India; and Asia Pacific (Australia, Hong Kong, North Korea, South Korea, Malaysia, Philippines, Singapore, Taiwan, New Zealand).
Study resultsNone of the analyses revealed any statistically significant differences in query rates or the rate of database change when each of the emerging-country regions was compared with North America or Western Europe, Desai et al reported.
They did, however, recognise the limitations of the study, such as the influence on query rates of trial complexity and frequency of monitoring; an imbalance in the number of sites and participants from different regions (e.g., data available for only four studies in China); lack of details on the nature of queries; and the existence of alternative quality parameters, such as measures specific to human participant protection (e.g., adverse-event reporting); or the frequency/findings of audits by trial sponsors, contract research organisations or regulatory agencies.