A Global Regulatory GPS?

Spurred by a reader request, Applied Clinical Trials recently tried to find one data source where we could pinpoint a sort of global regulatory GPS of ethics committee and competent authority approval. This type of GPS was not to be found. Peter O'Donnell, our View from Brussels columnist, noted: "The picture keeps changing, and there is so much variability from one trial to another that [a single data set] would probably be out of date before it was compiled. And that despite this, the maximum times for all these processes is supposed to be harmonized within the EU." Peter regularly writes about EU issues that cause conflict in this area.

Sample Of Regulatory Timelines

Excel Life Sciences, a clinical trial management organization (TMO) headquartered in Chicago that focuses on trials conducted in India, provided us with a global snapshot it recently compiled and analyzed (see chart). Applied Clinical Trials spoke with Vijai Kumar, MD, president and chief medical officer of Excel about the current Asian regulatory picture.

"Parts of Asia are increasing the number of trials they conduct. Korea, Thailand, Indonesia, Malaysia, Singapore, as well as India," said Kumar. "Malaysia has a very lax regulatory environment. In Indonesia, Malaysia, and Thailand, they have central IRB approval and for those countries, the ethics committee is more important than the Ministry of Health [regulatory authority]," said Kumar. "In fact, they consider the clinical trial materials and source more important than the protocol." On the other hand, in India, there is a well laid out and reasonably predictable timeline for both Ministry of Health and IRB approval. Ever since the Drugs Controller General of India started to categorize clinical trials, approval for global clinical trials with participating Indian sites takes four to six weeks, and, when India is the only country for a Phase II study of a compound developed outside India, the approval time is up to 12 weeks.

Knowing the competent authorities (CA) minimum and maximum review times is necessary. Couple that with the necessary Institutional Review Board (IRB) or ethics committee (EC) review times. Sometimes the CA/IRB/ECs are reviewed simultaneously (as in India or the previously mentioned Asian countries), and for other countries, such as China, approval from ECs does not happen without the CA.

Stewart Geary, MD, vice president and global safety officer for Eisai in Japan, and Applied Clinical Trials Editorial Advisory Board member, noted a similar situation in Japan. "Companies here typically go to the IRB/Ethics Committee for their review before applying to the Regulator because the IRB will also often ask for changes especially to the Informed Consent form. The review time for an IRB is short in the sense that a protocol is usually reviewed at a single meeting, but the company needs to match their application time to the schedule used by that Institution for holding IRB meetings and the IRB will want to receive materials in advance."

Which leads into the difference between review times and actual study start-up times. Actual study start-up time involves getting the clinical trial supplies licensed for import and approval, preparing the investigative sites, as well as the investigator meetings, so those additional times become a factor. For Thailand, Indonesia, and Malaysia, actual study start-up time is approximately an additional four months. For Singapore, it is six weeks. For China, which is sporting a nine to 12 month review, that additional preparation time translates to a study start-up of 14 to 16 months, according to Kumar.—Lisa Henderson