Draft guidance document on the collection and analysis of disaggregated data in clinical trials: Overview

Organization: Health Canada

Published: 2022-12-23

On this page

• Background
• Policy objective
• Policy statement
• Scope and application
• Terms and definitions
• Note about guidance documents in general

Background

This guidance will help sponsors interpret amendments to the Food and Drug Regulations (regulations) requiring them to submit clinical trial data disaggregated by sex, age and race/ethnicity if they have already done so as required by existing legislation or regulation in the United States or Europe.

It is standard practice to collect disaggregated subgroup data during drug development (for example, refer to the international standards outlined ICH M4E(R2)).

This guidance:

• sets out Health Canada's expectations
• supports our efforts to be transparent
• ensures that the provisions in the regulations on disaggregated data are interpreted consistently

The first part of this guidance document outlines how to comply with regulatory requirements for submitting disaggregated data. The second part of this guidance provides information and best practices related to collecting, analyzing and reporting on disaggregated data in clinical evidence, where applicable.

Disaggregated data is data obtained by breaking down aggregated datasets into subcategories. These subcategories are based on factors such as sex, age, race/ethnicity, co-morbidities and/or other patient demographics.

Disaggregating data is an important approach to data collection and analysis in drug development, as it:

• allows sponsors and Health Canada to assess the efficacy and safety of drug products in different subgroups
• ensures there is consistency with the overall results, where feasible
• indicates where more focused post-market monitoring may be needed to further verify safety and efficacy in certain populations after products are approved for sale in Canada

The collection and analysis of disaggregated data is at the core of Health Canada's sex and gender-based analysis plus (SGBA Plus) mandate.

SGBA Plus is an analytical process used to assess:

• how diverse groups of women, men and non-binary people may experience policies, programs and initiatives
• differences in how groups of people (subgroups) react to a specific drug in terms of both efficacy and safety

The "plus" in SGBA Plus acknowledges that SGBA goes beyond biological (sex) and socio-cultural (gender) differences. It indicates the importance of intersectionality, which refers to the multiple factors that intersect to make us who we are, such as:

• sex
• age
• race
• gender
• geographic location

Policy objective

Clinical trial participants should represent the population who will be using the drug. This is important as intrinsic (genetic, physiologic) and extrinsic (cultural, environmental) characteristics of a population, including age, sex and race/ethnicity, can lead to different treatment effects. Some, but not all, of the intrinsic and extrinsic factors that can impact a person's response to a drug product are known.

Patient populations are also often heterogeneous across many factors (for example, sex, age and race).

These factors highlight the importance of recruiting representative clinical trial participants so that data can be disaggregated and analyzed meaningfully by subgroups of interest (for example, sex, age, race, co-morbidities, and medication use).

Health Canada is leveraging experience in other jurisdictions by aligning with existing legislation and regulations of the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Learn more about intrinsic and extrinsic differences in the following guidance and studies:

• ICH E5: Ethnic factors in the acceptability of foreign data (ICH Harmonised Tripartite Guideline, PDF)
• ICH E8: General considerations for clinical studies (PDF)

Policy statement

The amendments to the regulations are intended to:

• receive disaggregated data and subgroup analyses that can help assess differences in key efficacy and/or safety parameters between clinically relevant, prognostic subgroups
• increase transparency by assessing and reporting on the diversity of clinical trial participants for each drug product

Scope and application

This draft guidance document is for sponsors who will be applying to Health Canada for market authorization for a drug for human use.

The scope of this guidance document includes drugs for human use. These drugs are regulated by the Health Products and Food Branch in accordance with the Food and Drugs Act and the regulations.

Terms and definitions

Disaggregated data: Data obtained by breaking down large-scale or aggregated datasets into subcategories, such as sex, age and race/ethnicity, or a combination of these (and/or other) subcategories.

Disaggregated data plan: A plan designed to support the collection and assessment of disaggregated data by age, sex, racial/ethnic groups and associated covariates. The plan is used to establish whether and how a treatment may affect the benefit-risk profile of specific subgroups.

Gender: The socially constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender-diverse people. It influences how people perceive themselves and each other, how they act and interact, and the distribution of power and resources in society.

Gender identity is not confined to a binary (girl/woman, boy/man) or static. It exists along a continuum and can change over time.

There is considerable diversity in:

• how individuals and groups understand, experience and express gender through the roles they take on
• the expectations placed on them
• a person's relations with others
• the complex ways that gender is institutionalized in society

Please refer to the following definition by the Canadian Institute of Health Research:

• What is gender? What is sex?

Heterogeneity assessment: An evaluation examining whether differences in treatment efficacy or safety are anticipated between subgroups of the overall study population. This assessment is a key aspect of clinical trial protocol design. It should describe the measures taken to establish whether there are, or could be, clinically important age, sex and racial/ethnic differences in response to study treatment.

Sex: A set of biological attributes in humans and animals. It is mainly associated with physical and physiological features, such as chromosomes, gene expression, hormone levels and function, and reproductive/sexual anatomy.

Sex is usually categorized as female or male, but there is variation in the biological attributes that comprise sex and how those attributes are expressed.

Sex differs from gender, which refers to the socially constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender-diverse people.

Note about guidance documents in general

Guidance documents provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. They also provide guidance to Health Canada staff on how mandates and objectives should be met fairly, consistently and effectively.

Guidance documents are administrative, not legal, instruments. This means that flexibility can be applied. However, to be acceptable, alternate approaches to the principles and practices described in this document must be supported by adequate justification. They should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, to help us adequately assess the safety, efficacy or quality of a therapeutic product. We are committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read in conjunction with the accompanying notice and the relevant sections of the Food and Drug Act and its Regulations and other applicable guidance documents.

Related links

Government of Canada

• What is gender-based analysis plus
• Guidance document: Considerations for inclusion of women in clinical trials and analysis of sex differences

FDA

• FDA disaggregated data requirements
• Guidance document: Diversity plans to improve the enrollment of participants from underrepresented racial and ethnic populations in clinical trials

EMA

• EMA disaggregated data requirements

ICH

• ICH guidelines in the safety and efficacy series