Notice

Our file number: 11-112316-337

Adoption of International Conference on Harmonisation (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use Guidance: E10: Choice of Control Group and Related Issues in Clinical Trials

Health Canada, as official observer to, and active participant in, the ICH, is committed to the adoption and implementation of ICH guidances. Health Canada, by this notice, is advising of its intent to implement the ICH guidance: Choice of Control Group and Related Issues in Clinical Trials (E10) .

This guidance was developed by the appropriate ICH Expert Working Group and was subject to consultation by the regulatory parties, in accordance with the ICH Process. ICH E10 has been implemented by the regulatory bodies of the United States, European Union, Japan, Switzerland and Australia.

The ICH guidance Choice of Control Group and Related Issues in Clinical Trials describes the general principles involved in choosing a control group for clinical trials intended to establish the efficacy of a new drug. These principles include both scientific and ethical considerations. Following extensive consultation by Health Canada and the Canadian Institutes of Health Research (CIHR) with their stakeholders through the National Placebo Initiative (NPI), Health Canada is adopting this ICH guidance and the overarching principles and practices described therein.

The ICH guidance should be applied in conjunction with this notice, as part of Health Canada's regulatory framework for clinical trials. This framework reflects both scientific and ethical considerations and additionally includes the Canadian requirements for clinical trials under the Food and Drug Regulations and applicable Health Canada and ICH guidance documents. The associated ICH documents include ICH E6: Good Clinical Practice: Consolidated Guideline. which identifies the ethical principles that define good clinical practice, and ICH E8: General Considerations for Clinical Trials and ICH E9: Statistical Principles for Clinical Trials. which articulate the general scientific principles and considerations in the design and analysis of clinical trials.

Health Canada recognizes that all clinical trials involve risk to participants. For all authorized trials,

the rights, safety and well-being of the participants need to be upheld under the specific conditions of the trial and the trial needs to be scientifically sound.

Risks to the safety of participants can come from lack of efficacy or from undesirable side effects. These risks must be assessed for each treatment arm, including the experimental and control arm(s). The choice of control arm, which may range from currently approved treatments to placebo, placebo add-on or no treatment, should not expose trial participants to undue risks and, as with other aspects of the trial design, should be justified based on scientific, medical and methodological reasons.

With respect to establishing the efficacy of a new drug, Health Canada considers the most compelling trial design to be a Randomised Controlled Trial (RCT). There are many possible variations and choices of control groups for RCTs, including but not limited to active control, placebo control, dose-response, multiple arms, and combination therapies. It is the responsibility of the trial sponsor to provide justification for the choice of control group. The ICH E10 guidance outlines the issues that should be considered when designing an RCT, as well as the implications of various design choices.

Sponsors are encouraged to refer to ICH E10 which explains the scientific basis and implications for various choices of control groups in clinical trials, and is consistent with the view of other federal regulators. With the adoption of ICH E10, it is Health Canada's position that compliance with Canadian regulatory framework for clinical trials will ensure an acceptable benefit-risk balance.

This and other Guidance documents are available on the Health Canada website.

Should you have any questions or comments regarding the content of the guidance, please contact:

Bureau of Policy, Science and International Programs

Therapeutic Products Directorate

Health Products and Food Branch

Health Canada

Holland Cross Tower B, 2 nd Floor

1600 Scott Street, Address Locator 3102C1