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Low Sexual Interest, Desire, and/or Arousal in Women: Developing Drugs for Treatment Guidance for Industry

DraftCenter for Drug Evaluation and Research10/25/2016

Description

The purpose of this guidance is to assist sponsors in developing drugs for the treatment of low sexual interest, desire, and/or arousal in women. Specifically, this guidance addresses the Food and Drug Administration’s (FDA’s) current thinking regarding the overall clinical development program, with a focus on phase 3 trial designs, to support an indication for the treatment of these conditions. This draft guidance is intended to serve as a focus for continued discussions among the Division of Bone, Reproductive, and Urologic Products, pharmaceutical companies, the academic community, and the public.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

1
therapeutic biological products

references to drugs include both human drugs and therapeutic biological products

Stakeholders

2
sponsor

responsible for justifying omission of studies

Pediatric age group

sponsors can request a full waiver for pediatric studies

Regulatory Context

Regulatory Activities

3
phase 3 trial

focus on phase 3 trial designs to support an indication

Phase 3 trials

Guidance describes recommendations regarding phase 3 trials for prescription non-opioid analgesic products.

FDA Development Tool Qualification program

framework for collaboration on PRO instruments

Document Types

4
patient-reported outcome instruments

Clinical outcome assessment tool used to collect patient data.

PRO instruments

providing reminders to trial subjects to complete PRO instruments

Electronic records

Records kept in electronic format subject to specific requirements.

PRO instrument

Patient-reported outcome instrument used for primary endpoints in phase 3 trials

Attributes

3
Content validity

evidence that the items and domains of an instrument are appropriate; FDA concerns with the content validity and response scale of the FSFI desire domain

recall period

long recall period (28 days) as discussed in section III.D.1

type I error

plan for controlling type I error for endpoints leading to labeling claims

Technical Details

Testing Methods

6
Female Sexual Function Index

Instrument for measuring patient-reported outcomes; 19-item instrument used in clinical trials to measure overall sexual function

Female Sexual Distress Scale-Revised, Item 13

Instrument for measuring patient-reported outcomes

MCP-MOD

a statistical methodology for dose response

Female Sexual Distress Scale-Revised

instrument considered acceptable for measuring bother related to decreased sexual desire

patient global impression of severity

static current-state anchor to evaluate the responder definition

patient global impression of change

anchor used in addition to the PGI-S to provide evidence in interpreting change

Processes

1
cardiac repolarization potential assessment

Development programs for all new molecular entities should include this assessment

Clinical Concepts

8
female sexual interest/arousal disorder

FSIAD is a clinical entity described in the DSM-5

hypoactive sexual desire disorder

HSDD is a condition described in the fourth edition of the DSM

female sexual arousal disorder

FSAD is a condition described in the fourth edition of the DSM

dyspareunia

guidance does not address the treatment of dyspareunia

vulvovaginal atrophy

often related to VVA associated with menopause

Sexual dysfunction

can adversely affect various aspects of life for a woman

FSIAD

Female Sexual Interest/Arousal Disorder

suicidal ideation and behavior

prospective assessment for drugs with a potential psychotropic mechanism

Standards & References

External Standards

1
Diagnostic and Statistical Manual of Mental Disorders

Used to define symptoms of MDD.

ICH References (5)

ICH E9

Statistical Principles for Clinical Trials; Discourages deterministic procedures due to high risk of bias; Notes that the use of Bayesian methods in clinical trials may be considered.

ICH E10

Choice of Control Group in Clinical Trials.

ICH E4

Dose-Response Information to Support Drug Registration

ICH E1

Regulatory standards for the extent of population exposure for treatments intended for long-term treatment

ICH E14

Clinical Evaluation of QT/QTc Interval Prolongation.

Related CFR Sections (3)

See Also (8)

Low Sexual Interest, Desire, and/or Arousal in Women: Developing Drugs for Treatment Guidance for Industry | Guideline Explorer | BioRegHub