Inexorably drug development is becoming—and in many ways, has already become—a global enterprise. Clinical research organizations (CROs) have not only benefited from this trend but have been major drivers behind globalization as the need for ever-larger and more complex clinical trials must be balanced with a desire for speed and efficiency. Accessing a global population of participants is a necessity to meet the demands of today’s drug development paradigm.
A July 2009 whitepaper commissioned by the Association of Clinical Research Organizations (ACRO) titled “The Case for Globalization: Ethical and Business Considerations for Clinical Research” found that globalized trials can reduce development time by half while lowering costs and maintaining quality and safety. For example, phase III cancer trials are conducted three times as fast if both U.S. and global sites are used, compared to U.S.-only sites. What takes 5.8 years to enroll takes 1.9 years when a global trial is implemented.
Table 1: Number of Patients Enrolled per Active Trial Site: Established versus Emerging Markets1
| Established Markets |
Patients per active site 2008 |
Change (in patients) since 2006 |
|
France |
7.6 |
+1.3 |
|
Germany |
8.3 |
+1.5 |
|
United Kingdom |
8.1 |
+2.5 |
|
Canada |
6.5 |
+0.3 |
|
United States |
5.7 |
+0.4 |
|
Average Above Countries |
7.2 |
+1.0 |
|
Emerging Markets |
Patients per active site 2008 |
Change (in patients) since 2006 |
|
Eastern Europe |
13.0 |
+2.6 |
|
Latin America |
11.4 |
+2.3 |
|
Asia |
11.1 |
+0.1 |
|
Average Above Regions |
11.8 |
+1.7 |
| Les Entreprises du Medicament (LEEM). (2008). The attractive position of France in International Clinical Research: 2008 survey assessed by Leem. Paris, France. | ||
While CROs have performed the role of international standard setters in regard to the implementation of uniform research practices and International Conference on Harmonisation-Good Clinical Practices (ICH-GCP) adoption, often the global regulatory infrastructure has not kept pace with research needs.
Nevertheless, there is no evidence to suggest that the quality of the data and the overall research conducted outside the established pharmaceutical markets of North America and Western Europe is of lesser quality. In fact, from studies that have analyzed regulatory audit findings and error rates in reporting, the evidence is clear that there are not discernable differences in quality and, in some cases, that research quality from emerging countries exceeds that of established countries.
Table 2: Results of FDA Clinical Investigator Inspections 2000-082
|
|
No Action Required |
Voluntary Action Required |
Official Action Indicated |
Total |
|
Africa |
41% |
59% |
0% |
29 |
|
Asia/Pacific, other |
63% |
38% |
0% |
16 |
|
Australia/New Zealand |
50% |
50% |
0% |
4 |
|
Canada |
33% |
67% |
0% |
94 |
|
Central, Eastern Europe |
42% |
57% |
1% |
183 |
|
China |
6% |
94% |
0% |
17 |
|
India |
40% |
60% |
0% |
10 |
|
Japan |
100% |
0% |
0% |
1 |
|
Korea |
0% |
100% |
0% |
2 |
|
Latin America |
31% |
67% |
3% |
117 |
|
Middle East |
18% |
73% |
9% |
11 |
|
US |
25% |
65% |
10% |
4,014 |
|
Western Europe |
25% |
74% |
1% |
314 |
|
Total |
1,248 |
3,157 |
407 |
4,812 |
| VOI Consulting analysis of data found in FDA Investigational Human Drugs Clinical Investigator Inspection List, Retrieved May 18, 2009, from https://www.fda.gov/CDER/Offices/DSI/clinInvestList.htm | ||||
VOI Consulting analysis of data found in FDA Investigational Human Drugs Clinical Investigator Inspection List, Retrieved May 18, 2009, from https://www.fda.gov/CDER/Offices/DSI/clinInvestList.htm
One reason for the growing consistency in quality globally is that many emerging countries have adopted, or are in the process of implementing, regulations to ensure that clinical trials are conducted in a quality manner with an emphasis on ethics and participant safety.
CROs and research sponsors alike welcome these new regulations as they add certainty, consistency and confidence to the clinical research endeavor. ACRO, as the voice of the global CRO industry, pays acute attention to these regulatory developments ranging from Italy to India and Turkey to China.
Some of the more recent international regulatory developments have included:
Italy
The Italian Authority (AIFA) adopted a Ministerial Decree that aims to define minimum requirements for CROs doing business in Italy. In part, the Decree requires the confirmation of educational, training, and experience requirements for clinical trial monitors.
India
India’s Central Drugs Standard Control Organization recommended that all clinical research organizations carrying out clinical trials on behalf of pharmaceuticals and medical device companies be required to register with the government. Registration would cover all organizations, individuals, and companies with responsibility for managing or coordinating a clinical trial. Registration, which would be valid for up to five years, would be granted on the condition that the individual or organization was thoroughly familiar with the product, protocol, content of participant consent forms, GCP guidelines, and other pertinent information. The organizations would have to show that they have adequate resources and well-trained staff, and they would have to train staff on protocol adherence, informed consent, and responding to research subjects’ concerns. The guidance is in the process of being finalized.
China
China’s State Food and Drug Administration (SFDA) issued review and inspection standards for the “qualification confirmation” of institutions conducting clinical trials. A qualification confirmation involves more detailed scrutiny than the certification program for clinical study institutions. Unlike certification guidelines, it includes inspection guidelines and checklists for confirming the qualifications of both clinical study institutions and individual departments within those institutions.
Singapore
The Singapore Health Sciences Authority (HSA) has launched a new inspection framework aimed at ensuring clinical trial sites comply with Good Clinical Practices (GCP). A main focus is to verify the quality and integrity of the clinical trials data submitted to the agency. GCP site inspections of contract research organizations and/or sponsor organizations will either be routine, triggered by complaints, or in response to a pre-marketing authorization approval application.
These developments are entirely consistent with the recommendations that accompanied the ACRO whitepaper. Specifically, that:
• The U.S Food and Drug Administration be provided sufficient resources to conduct inspections on a global basis in order to ensure that research quality is protected and improved around the world.
• All governments take measures to foster the development of a clinical research infrastructure and encourage clinical research participation.
• Overseas regulatory bodies recognize drug development as a global enterprise and that globalization leads to faster cures.
• All participants in clinical research—no matter where they live or the environment in which research takes place—be protected by the same level of safety and ethical considerations, and that they be afforded the same standard of care, including adherence to the GCP principles promulgated by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
Doing business on a global scale with myriad regulations is not a simple endeavor. Yet, CROs, research sponsors, and other stakeholders in the drug development process understand and accept that a strong international regulatory regime ultimately results in safe and effective therapies being brought market sooner.
About the Author
Doug Peddicord, PhD, serves as Executive Director of the Association of Clinical Research Organizations, Washington, DC.
References
1. Les Entreprises du Medicament (LEEM). (2008). The attractive position of France in International Clinical Research: 2008 survey assessed by Leem. Paris, France.
2. VOI Consulting analysis of data found in FDA Investigational Human Drugs Clinical Investigator Inspection List, Retrieved May 18, 2009, from https://www.fda.gov/CDER/Offices/DSI/clinInvestList.htm.
Filed Under: Drug Discovery
