Sex Differences and Implications for Translational Neuroscience Research: Workshop Summary (2011)

Background: Basic research that involves delineating meaningful drug effects and behavioral and physiological responses that differ between the sexes can be costly and time consuming because the research requires additional experiment groups and protocols. However, epidemiological and clinical studies indicate substantial sex differences in response to drugs. The sex differences cut across other parameters such as socioeconomic factors, race, age, etc. In the current era of translational research and personalized medicine, taking sex differences into account is important so that these drug effects can be more accurately understood. This is particularly important in the neurosciences because of the complex nature of many disorders of the nervous system, including mental, neurological, and substance use disorders. Consequently, the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders is hosting a workshop to explore the key principles and strategies used by basic translational researchers and industry in studying sex differences in the neurosciences for the therapy development pathway.

Meeting Objectives: The objectives of this workshop are to

• briefly outline the public health importance of studying sex difference in the nervous system, in health and sickness, including the potential application to healthcare delivery;

• identify the scientific principles that should be considered when designing preclinical experiments that will examine sex differences, including strategies to bridge between preclinical and clinical studies;

  • discuss when and how sex differences should and should not be considered;

• explore the key principles and strategies used by academic clinicians to effectively use basic research for preclinical and clinical application and study (i.e., Phases 0–IV), including approaches used by researchers to decide how and when to consider the potential importance of sex differences;

• explore how and when industry considers and addresses studying sex differences, given regulatory guidelines;

• examine the advantages, constraints, and implication of performing “valid analysis” versus requiring statistical outcomes between the sexes;

• identify the next steps that will be critical to establishing a set of principles that could be used by a variety of stakeholders in considering when and how to incorporate studying sex differences into translational research efforts.

March 8, 2010

Franciscan Ballroom

Sir Francis Drake Hotel

450 Powell Street, San Francisco, CA

Session Objectives:

• Briefly outline the public health importance of studying sex difference in the nervous system, in health and sickness, including the potential application to healthcare delivery.

• Identify the scientific principles that should be considered when designing preclinical experiments that will examine sex differences, including strategies to bridge between preclinical and clinical studies.

  • Discuss when and how sex differences should and should not be considered.

• Explore the key principles and strategies used by academic clinicians and industry to effectively use basic research for preclinical and clinical application and study (i.e., Phases 0–IV), including approaches used by researchers to decide how and when to consider the potential importance of sex differences.

Opening Remarks

Session Objectives: Based on today’s presentations and discussions, a panel will synthesize and discuss key points and ideas that examined

• the principles that should be considered when designing preclinical experiments that will examine sex differences, including strategies to bridge between preclinical and clinical studies;

  • when and how sex differences should and should not be considered;

• the key principles and strategies used by academic clinicians and industry to effectively use basic research for preclinical and clinical application and study (i.e., Phase 0–IV), including approaches used by researchers to decide how and when to consider the potential importance of sex differences.

March 9, 2010

Session Objectives:

• Discuss regulatory practices regarding the inclusion of males and females in clinical trials.

• Explore how and when industry considers and addresses studying sex differences, given regulatory guidelines.

• Identify industry’s constraints on assessing sex differences in all phases of clinical trials.

• Examine the advantages, constraints, and implications of performing “valid analysis” versus requiring statistical outcomes between the sexes.

Session Objectives: Identify the next steps that will be critical to establishing a set of principles that could be used by a variety of stakeholders in

considering when and how to incorporate the study of sex differences into research.

Wrap-Up Discussion Questions:

1. What are the key opportunities where understanding sex differences will have the greatest healthcare impact?

2. What are some of the critical factors (e.g., biological, epidemiological, health economics, sociological, ethical) and how would they guide the consideration of studying sex differences to improve health care?

3. When and how should sex differences in disease susceptibility be studied?

4. When and how should sex differences in drug response be studied?

5. What are some of the barriers that impede sex differences research and how can they be overcome?

6. How can academic clinicians and basic researchers help improve translational neuroscience efforts in the area of sex differences research?

7. What factors will affect the successful translation of sex differences from preclinical to clinical studies?