CIOMS to publish DSUR on safety reporting for clinical trials in 2nd quarter 2006.

WASHINGTON--The Council for International Organizations of Medical Sciences VI Working Group (CIOMS IV) plans to publish the "Development Safety Update Report (DSUR): A Harmonized Approach to Periodic Safety Reporting During Clinical Trials" in the second quarter of 2006, a senior pharmaceutical consultant said here Jan. 25.

Arnold Gordon, Ph.D., noted at a Drug Information Assn. (DIA) meeting on pharmacovigilance and risk management strategies, that the intent of the DSUR is to harmonize FDA's IND annual report and the European Union's (EU) clinical trial directive's annual safety report. He also stated that the DSUR will consist of one annual report for all regulators who require them. Also, it will utilize standard format, content and timing similar to the International Conference on Harmonization (ICH) E2C PSUR.

"The scope of the DSUR is to summarize all relevant, new safety-related information, and to provide a cumulative summary of key safety findings," he said. It also will provide an update on emerging urgent safety issues, and provide the latest version of the Development Core Safety Information (DSCI).

CIOMS, which first met in March 2001, consists of 25 industry and regulatory members from the U.S., Europe, Australia and Japan. The scope of the group's work is to increase public and professional awareness of clinical trial safety and ethics. Also, it increases legislative awareness of trial safety, and attempts to resolve inconsistent practices and regulatory ambiguities.

Gordon stressed that CIOMS does not have any official regulatory or other authority. "It influences and persuades by the strength of its ideas and by its credibility," he said.

Stakeholders in CIOMS include FDA, Health Canada and the European Agency for the Evaluation of Medicinal Products, plus companies, such as, Bayer, Eli Lilly, Pfizer, Wyeth, AstraZeneca, Merck, and GlaxoSmithKline.

The working group also is focusing on other areas that have been confronting the clinical trial field for years. These include ethical considerations for clinic trial management, a systematic approach to managing safety, collection and management of data, identification and evaluation of risk, statistical analysis of safety data, and regulatory reporting and other communication.

Other areas the group is considering for recommendations are:

* Clinical trials in non-industrialized developing countries;

* Potential conflicts of interest that may affect the integrity of research;

* Is informed consent always necessary?

* Confidentiality and the protection of personal data; and

* Transparency of results and outcomes for all trials.

"We also are striving to identify, evaluate and minimize potential safety risks to subjects and patients during clinical trials," Gordon said. Additionally, CIOMS is developing the appropriate level of safety knowledge from trials to optimize post-marketing safe use. "We view this as an attempt to build a bridge between ICH E2E, and to complement FDA guidances on the subject."

On the systematic approach to managing safety, he noted that CIOMS recommends "a well-defined, well-structured process," that should "readily identify, evaluate and minimize potential risks for study subjects." The process, he added, should start before Phase I initiation and continue through approval and marketing. A formal risk management plan also should be considered.

A risk management plan is an internal guide for safety surveillance during development, Gordon said. It is not intended for regulatory submission. It should include early documentation of known, anticipated or potential risks, along with plans for addressing them during development. "It could eventually evolve into a postmarketing risk management plan," he noted.

In the collection of safety data, Gordon said the working group is considering these points:

* Can one collect too much data?

* How is safety information solicited from patients?

* Laboratory data

* Unexpected pregnancy

* Signs and symptoms vs. diagnosis

* Investigator's causality assessment

* Safety vs. morbid/mortal efficacy endpoints

* Post-study follow-up

Gordon said, "The start of collection of safety data should be specified in the protocol." Some scenarios include baseline data from the time the patient signs informed consent, or at the time of first protocol-specific intervention.

However, currently there are no standards regarding when data should no longer be collected. "CIOMS recommends at least an additional five half-lives after the last dose." Beyond that, Gordon said, only serious adverse events (SAEs) with a suspected causal relationship should be considered.

By Joseph Pickett Managing Editor