Considering Sex-Specific Variation for Personalized Medicine

by Foley & Lardner LLP
Contact

Personalized medicine may use devices and assays that identify sex-related differences. For example, a device or an assay may determine if a cancer patient harboring a particular genetic variance will or will not respond to a particular cancer therapy. In some instances, the prediction of clinical outcome is related not only to the genetic variance but also to the sex of the patient.

The Food and Drug Administration (FDA) recently issued a new guidance for industry and FDA staff that may be relevant in the design and development of medical devices that serve personalized medicine, especially those that categorize patients into responders and non-responders. “Evaluation of Sex-Specific Data in Medical Device Clinical Studies” (Guidance) should be carefully reviewed by clinical device manufacturers, especially manufacturers of devices that separate individuals into two or more groups, such as those that respond to a particular treatment and those that do not respond. The Guidance is intended for devices that require clinical information in support of a marketing submission, whether a premarket notification (510(k)), premarket approval (PMA), a de novo request, or a humanitarian device exemption application. The recommendations reported in the Guidance also apply to post-approval study submissions and postmarket surveillance.

Sex Versus Gender

Sex as defined by the Guidance, is the classification of living things, generally as male or female according to their reproductive organs and functions assigned by chromosomal complement. Guidance, page 3. In contrast, gender is defined as a persons self-representation as male or female or how social institutions respond to that person.

The Guidance notes that the recommendations suggested therein do not create or confer any rights for or on any person and does not operate to bind the FDA or the public. The Guidance represents the FDAs current expectations regarding sex-specific patient enrollment, data analysis, and reporting of study information. The stated primary intent is to improve the quality and consistency of available regarding the performance of medical devices in both sexes by encouraging appropriate enrollment by sex in clinical studies of devices, and that data from such studies is appropriately analyzed by sex. Guidance, page 1.

Does Sex Make a Difference?

The Guidance acknowledges that certain medical products elicit different responses in women as compared to men. These differences may be attributed to intrinsic factors (such as genetics, hormones or body size) or extrinsic factors (such as diet, sociocultural issues or environment) or an interaction between these. It is also known that men and women report outcomes such as pain, differently. Moreover, fewer women historically have been enrolled in many clinical studies that have led to a lack of information available for women and their doctors regarding the risks and benefits of medical treatments and diagnostic procedures.

Recommendations for Clinical Studies

Sponsors of clinical studies for medical devices are encouraged to enroll representative proportions of women and men to achieve an unbiased estimate of treatment effect in the general population. However, where disease science or prior clinical study results suggest treatment effects for a medical device or treatment in only one sex, then sponsors are encouraged to intentionally enroll sufficient numbers of patients to support a valid analysis.

The Guidance suggests that sponsors of medical device clinical studies investigate whether sex differences may or may not exist for the disease or conditions that the device is intended to treat or diagnose in the following areas:

  • Sex-specific prevalence;
  • Sex-specific diagnosis and treatment patterns;
  • Identification of proportions of women included in past studies for the target indication; and
  • Identification of any known clinically meaningful sex differences in outcome related to either safety or effectiveness.

Guidance, page 9.

The Guidance recommends the use of sex-specific information in the design and conduct of clinical trials in several scenarios: for new or ongoing studies of medical devices; in the marketing application; and in any post market studies of the device. Investigation of heterogeneity across sex group should be conducted to account for any differences in how a device performs in women versus men in terms of safety and effectiveness.

Special Consideration for Diagnostic Assays and Devices That May Be Used for Personalized Medicine

Personalized medicine may use diagnostic devices and assays that use a cutoff. The Guidance notes that an assay or device involves a cutoff whenever a continuous or ordinal measurement is used to separate patients into two or more categories (for example, responders and non-responders). The Guidance recommends that separate cutoffs for men and women should be used only when there is reason to believe separate cutoffs are needed based on prior evidence.

Recommendations for Analysis and Interpretation in Completed Studies

The Guidance also recommends that in general, all studies should report descriptive statistics for outcomes of interest, e.g., the estimate of variance or standard deviation (as applicable), by sex. Sponsors are encouraged to examine data for clinically meaningful sex differences in each of: primary effectiveness endpoint(s); primary safety endpoint(s); and key secondary endpoints.

Implementation and Comment

Detailed information for the reporting sex-specific information in device applications can be found in the Guidance as well as recommendations for analysis and interpretation of sex-specific data.

The public may submit written comments and suggestions at any time for the FDA’s consideration to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. Electronic comments may be submitted to http://www.regulations.gov. All documents must be identified with the docket number FDA-2011-D-0817.

View This Blog

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

© Foley & Lardner LLP | Attorney Advertising

Written by:

Foley & Lardner LLP
Contact
more
less

Foley & Lardner LLP on:

Readers' Choice 2017
Reporters on Deadline

"My best business intelligence, in one easy email…"

Your first step to building a free, personalized, morning email brief covering pertinent authors and topics on JD Supra:
Sign up using*

Already signed up? Log in here

*By using the service, you signify your acceptance of JD Supra's Privacy Policy.
Privacy Policy (Updated: October 8, 2015):
hide

JD Supra provides users with access to its legal industry publishing services (the "Service") through its website (the "Website") as well as through other sources. Our policies with regard to data collection and use of personal information of users of the Service, regardless of the manner in which users access the Service, and visitors to the Website are set forth in this statement ("Policy"). By using the Service, you signify your acceptance of this Policy.

Information Collection and Use by JD Supra

JD Supra collects users' names, companies, titles, e-mail address and industry. JD Supra also tracks the pages that users visit, logs IP addresses and aggregates non-personally identifiable user data and browser type. This data is gathered using cookies and other technologies.

The information and data collected is used to authenticate users and to send notifications relating to the Service, including email alerts to which users have subscribed; to manage the Service and Website, to improve the Service and to customize the user's experience. This information is also provided to the authors of the content to give them insight into their readership and help them to improve their content, so that it is most useful for our users.

JD Supra does not sell, rent or otherwise provide your details to third parties, other than to the authors of the content on JD Supra.

If you prefer not to enable cookies, you may change your browser settings to disable cookies; however, please note that rejecting cookies while visiting the Website may result in certain parts of the Website not operating correctly or as efficiently as if cookies were allowed.

Email Choice/Opt-out

Users who opt in to receive emails may choose to no longer receive e-mail updates and newsletters by selecting the "opt-out of future email" option in the email they receive from JD Supra or in their JD Supra account management screen.

Security

JD Supra takes reasonable precautions to insure that user information is kept private. We restrict access to user information to those individuals who reasonably need access to perform their job functions, such as our third party email service, customer service personnel and technical staff. However, please note that no method of transmitting or storing data is completely secure and we cannot guarantee the security of user information. Unauthorized entry or use, hardware or software failure, and other factors may compromise the security of user information at any time.

If you have reason to believe that your interaction with us is no longer secure, you must immediately notify us of the problem by contacting us at info@jdsupra.com. In the unlikely event that we believe that the security of your user information in our possession or control may have been compromised, we may seek to notify you of that development and, if so, will endeavor to do so as promptly as practicable under the circumstances.

Sharing and Disclosure of Information JD Supra Collects

Except as otherwise described in this privacy statement, JD Supra will not disclose personal information to any third party unless we believe that disclosure is necessary to: (1) comply with applicable laws; (2) respond to governmental inquiries or requests; (3) comply with valid legal process; (4) protect the rights, privacy, safety or property of JD Supra, users of the Service, Website visitors or the public; (5) permit us to pursue available remedies or limit the damages that we may sustain; and (6) enforce our Terms & Conditions of Use.

In the event there is a change in the corporate structure of JD Supra such as, but not limited to, merger, consolidation, sale, liquidation or transfer of substantial assets, JD Supra may, in its sole discretion, transfer, sell or assign information collected on and through the Service to one or more affiliated or unaffiliated third parties.

Links to Other Websites

This Website and the Service may contain links to other websites. The operator of such other websites may collect information about you, including through cookies or other technologies. If you are using the Service through the Website and link to another site, you will leave the Website and this Policy will not apply to your use of and activity on those other sites. We encourage you to read the legal notices posted on those sites, including their privacy policies. We shall have no responsibility or liability for your visitation to, and the data collection and use practices of, such other sites. This Policy applies solely to the information collected in connection with your use of this Website and does not apply to any practices conducted offline or in connection with any other websites.

Changes in Our Privacy Policy

We reserve the right to change this Policy at any time. Please refer to the date at the top of this page to determine when this Policy was last revised. Any changes to our privacy policy will become effective upon posting of the revised policy on the Website. By continuing to use the Service or Website following such changes, you will be deemed to have agreed to such changes. If you do not agree with the terms of this Policy, as it may be amended from time to time, in whole or part, please do not continue using the Service or the Website.

Contacting JD Supra

If you have any questions about this privacy statement, the practices of this site, your dealings with this Web site, or if you would like to change any of the information you have provided to us, please contact us at: info@jdsupra.com.

- hide
*With LinkedIn, you don't need to create a separate login to manage your free JD Supra account, and we can make suggestions based on your needs and interests. We will not post anything on LinkedIn in your name. Or, sign up using your email address.
Feedback? Tell us what you think of the new jdsupra.com!