Discussions
on diversity:
Gender identity

1 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

Within clinical research, patient diversity is critically important.
Inclusive studies move us closer to health care equity. They also
more accurately reflect real-world populations. To understanda drug as fully as possible, researchers must study it in a broad
range of patients, including people from underrepresented
communities, to reflect the patient population who will
ultimately be treated with the new medication or device.

Among clinical research’s
underrepresented groups:
transgender and nonbinary people.
One study estimates there are 1.6
million transgender people in the
U.S. alone and about one-quarter of
those people identify as nonbinary.
In clinical trials, these communities
have been nearly unaccounted for.
This is likely due in part because
both hospital electronic healthrecords and industry electronic data
capture systems do not routinely
track their involvement. Also, transand nonbinary people havehistorically faced practical barriers toparticipation. Now, encouragingly,
there is greater societal awarenessof the needs of the trans andnonbinary community, meaning a
new focus is emerging on improving
their access to clinical trials.

Guided by the dual goals of greater
understanding and wider inclusion,
Parexel set out to investigate thekey barriers to gender diversity
in clinical research. Throughcollaborative work, including an
extensive literature review anddiscussions with a patient advisory
council, we identified five typesof barriers to participation. Using
those findings, we explored possible
solutions, developing practical
recommendations for making
clinical research more accessible
for and welcoming of trans andnonbinary people.
One study estimates there are

1.6 million

transgender people in the U.S. alone and about
one-quarter of those people identify as nonbinary
2 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

Key terms for common understanding
Issues related to gender diversity and identity are complex and nuanced. To thoughtfully engage on these issues, it’s important tohave a shared understanding of some terms specific to trans and nonbinary people. Knowing how to interpret and use communityspecific language will allow for more informed, respectful discussions.

A transgender person is someone whose gender identity is different fromtheir sex assigned at birth. A transgender person may identify as male, female,neither, or a combination of both. Transgender is often shortened to “trans.”
A nonbinary person is someone who does not identify as either exclusively
male or female. Some people who are nonbinary experience their gender asboth man and woman, and others experience their gender as neither man
nor woman. Nonbinary can also be used as an umbrella term, encompassing
many other gender identities.
A pronoun is a word used to refer to people. Since some pronouns are
gendered (“she/her” and “he/him”), pronouns are connected to gender
expression. Examples of gender-neutral pronouns include they/themor ze/hir.

Gender non-conforming describes people whose gender expression differsfrom conventional expectations of masculinity and femininity. Gender
non-conforming expression can be used to describe cisgender, nonbinary
and transgender people.
Transition is the process of living according to one’s gender identity rather
than sex assigned at birth. (This process is also known as gender affirmation.)
Some people transition socially, which might include choosing a new nameand pronouns, telling family, friends and co-workers, or dressing differently.
Some people transition legally, meaning they have their chosen name and/or
affirmed gender listed on official documents like passports, licenses, or birthcertificates. Some people choose to medically transition, which could include
gender-affirming hormone therapy and/or gender-affirming surgery. Not alltrans people choose to transition and every transition is unique.

Sex assigned at birth is the label (either male or female) given to a baby
at birth, generally based on external anatomy.
Gender identity is someone’s internal, personal sense of possessing agender — whether male, female, both or neither.
Gender expression is the way a person demonstrates their gender
identity to others. Name, appearance and mannerisms can all be partof gender expression.

3 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

Knowing how to interpret anduse community-specific language
will allow for more informed,
respectful discussions.

Gender dysphoria is caused when there is a conflict between the sex
assigned at birth and the gender that a person identifies. Gender dysphoria
can create clinically significant distress and can make the individual feel
uncomfortable in their body. People with gender dysphoria may havechanged their appearance, their behavior or their interests. They may also
show signs of discomfort or distress, including, but not limited to, low
self-esteem, becoming withdrawn or socially isolated, depression or anxiety,unnecessary risk taking, and neglecting themselves.
Gender-affirming hormone therapy and gender-affirming surgery are
medical treatments and procedures that help a person take on physicalcharacteristics that match their gender identity.

Sexual orientation describes a person’s sexual or romantic/emotional
attraction to another person. Sexual orientation is not the same as gender
identity. Transgender and nonbinary people can be lesbian, gay, bisexual,
heterosexual, or any other orientation on the sexuality spectrum.
A cisgender person is someone whose gender identity aligns with his or her
sex assigned at birth. Cisgender is often shortened to “cis.”
A gender binary is the idea that there are only two distinct and separate
genders: male and female.

Chosen name is the name a person wants to be known by. Chosen names
may differ from legal names used on IDs and insurance documentation. A
person who has transitioned and selected a new name might refer to their
old name as a deadname.

Additional terms related terms can be found on
the Human Rights Campaign glossary of terms
or the Stonewall list of terms

4 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

4

Barriers to
overcome

To better understand barriers to trial participation for trans andnonbinary people, we took a mixed-method approach to research,
reviewing scientific literature published and convening a patientadvisory council composed of trans and nonbinary people.

From January 2018 to July 2022, 141,661 articles were published on PubMedreporting interventional clinical trial results. Fewer than one percent (107
articles) reported study participation of transgender and nonbinary patients.
A second search — conducted via MEDLINE, Biosis Previews, EMBASE,
SciSearch, and International Pharmaceutical Abstracts databases — resulted
in about 300 articles that discussed barriers to health care access fortransgender and nonbinary people. Approximately 50 articles reported
barriers to inclusion within clinical research.
Based on this quantitative research and detailed input from our patientadvisory council, we identified a range of barriers that deter gender
diversity in clinical trials.

5 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

1 Practical
32%

of trans people polled
reported unequal
treatment during
health careinteractions

According to a 2018 Stonewall report conducted in the U.K., 32 percent
of trans people polled reported unequal treatment during health careinteractions. The State of the LGBTQ Community in 2020 survey found thatnearly one-third of transgender people postponed or avoided medical carebecause they feared discrimination. Given such experiences, many trans andnonbinary people have deep reservations about using health care services— and patients who distrust the health care system are likely to havemisgivings about clinical research as well.
Similar experiences and concerns were documented in scientific literature.
In studies that discussed barriers to health care, trans and nonbinary
people often reported stigmatization, discrimination, and disrespect frommedical personnel. Discrimination ranges from verbal harassment to denialof medical care but was also reported to occur in less overt ways such asuse of incorrect pronouns or inappropriate curiosity about gender identity
or anatomy. Patients also reported that payers might deny coverage oftransition-related care and that they encountered few medical professionals
with extensive knowledge of trans and nonbinary patients’ specific andunique healthcare needs.
When asked about their experiences with clinical research, trans andnonbinary people often reported worrying that the risks of a study would
outweigh its benefits. They also questioned whether studies were aligned

6 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

with the values and needs of gender-diverse people.
Our patient advisory panel echoed many of these concerns, agreeing thatnegative experiences within the medical system are likely to deter trans andnonbinary people from seeking necessary care. They also noted that manytrans or nonbinary people who are undergoing gender-affirming hormone
therapy or surgery could have existing — and sometimes challenging —health care needs. Those people might not be able or willing to make time
for clinical study visits in addition to ongoing transition-related care.
Gender identity is nuanced but for medical and research purposes, patientsare generally categorized using binary gender labels. Gender binaries
are almost always built into clinical study protocols, starting with genderspecific inclusion criteria. Intake forms, administrative health data, andsampling methods also tend to assume that participants will be cisgendermen or women. Such requirements and forms rarely distinguish between
gender identity and sex assigned at birth, nor do they offer respondents theopportunity to report their chosen name and pronouns. When trans andnonbinary people report feeling unwelcome at medical and clinical researchfacilities, these are some of the issues they cite.
Also cited as a barrier to some patients considering clinical research
participation is the issue of gender-segregated areas inside medical andresearch buildings. For instance, clinics often lack gender-neutral restrooms
even though many trans and nonbinary people feel unsafe using genderspecific facilities. For studies that require overnight stays, trans andnonbinary patients might also be assigned to a gender-specific room or wardthat doesn’t match their identity, or report concerns if their fellow patientswere to react negatively towards them if they were to assigned to areas that
do match their gender identity.
People with diverse gender identities also report that medical and researchprofessionals too often are unfamiliar with inclusive practices, such as asking
for a person’s chosen name and/or pronouns or discussing anatomy withsensitivity. In a recent survey of physicians, more than 60 percent reported
they either had no training in transgender health issues or had been trained
only informally (such as through self-study).

7 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

Gender binaries are almost always built
into clinical study protocols, startingwith gender-specific inclusion criteria.
Intake forms, administrative healthdata, and sampling methods also tend
to assume that participants will becisgender men or women.

In one U.S. survey oftransgender people, nearly

1/2

reported receiving gender-affirming
hormone therapies

Currently, the medical and scientific community has minimal data available
about how transgender and nonbinary patients respond to new medications
as compared with cisgender patients.

2

Medical andscientific

In one U.S. survey of transgender people, nearly half reported receiving
gender-affirming hormone therapies. A handful of studies have found thattransgender patients can safely receive medication doses consistent with
their gender identity within as few as three months of beginning genderaffirming hormone therapies. But such studies have been infrequentand often use opportunity sampling. There’s also a lack of evidence
regarding possible impacts of gender-affirming hormone therapies on bodycomposition, drug metabolizing enzyme activity, and kidney function — data
that’s critical for creating safe dosing guidelines.
Due in part to that lack of data, dosing guidelines are usually developed only
for cisgender male and female patients.
We also found that when clinical research did include gender-diverse
people, statistical analyses were usually not powered to offer generalizable
results by the small sample size of the transgender patient group.

8 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

3 EthicalThe dearth of dosing information discussed above creates ethical challenges.
Underdosing and overdosing can both have significant safety consequences
for patients. Until enough data exists to create accurate dosing guidelines
for people using gender-affirming drug treatments, is it ethical to recruit
these patients? On the other hand, excluding trans and nonbinary people
from studies of beneficial medicines also raises ethical alarms. It is also thecase that trans and nonbinary patients will also already be participants inclinical research, but data on their inclusion and specific outcomes is notcollected or shared to advance universal knowledge within the medical andscientific community.
When asked whether they were concerned more about safety or inclusivity,
our patient advisory council members universally agreed that bothconsiderations are equally important.

When asked whether they were concerned more about safety
or inclusivity, our patient advisory council members universally
agreed that both considerations are equally important.

9 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

In April 2022, the United States Food and Drug Administration (FDA)
released a new draft guidance to encourage the biopharmaceutical industry
to implement diversity plans. The guidance, however, focuses only on raceand ethnicity. Whilst this in itself is an issue of critical importance and while
the guidance advises sponsors to seek diversity in other underrepresented
populations, it mentions gender identity briefly and only once. In theprevious guidance on diversity, the FDA recognized the distinction between
gender identity and sex assigned at birth but also deemed the matter
outside the guidance’s scope. And European Medicines Agency (EMA)
regulation 536/2014, which establishes rules on how clinical trials can be
conducted in the European Union, makes no distinction between gender
identity and sex assigned at birth.

4

Regulatory
and legal

10 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITYIn April 2022, the National Academies of Sciences, Engineering, andMedicine (NASEM) acknowledged that gender identity is not a binary
measure, noting that sex and gender are often conflated. NASEM — aligned
institutions that provide independent, objective policy advice — offered
recommendations for collecting data on sex assigned at birth, gender
identity, and sexual orientation in different settings, including clinical trials.
The World Professional Association for Transgender Health (WPATH) also
articulates Standard of Care for the health of transgender and gendernonconforming people. And while such recommendations are encouraging,clinical researchers rely on guidance from regulatory authorities — sountil these agencies provide detailed guidelines and requirements aroundgender identity and sex assigned at birth, it will be challenging to achieve
meaningful industry-wide change.
Thinking in the global context of clinical research, it should also be notedthat being transgender or nonbinary is deemed illegal in some countries.
During study planning it is therefore critical to take this worldwide legal
landscape into consideration so that the positive intent of optimizing healthequity for members of the trans and nonbinary community does
not inadvertently endanger patients.

Practical recommendations formore inclusive studies
Achieving equitable access to clinical research for gender-diverse people will require dedicated effort over time. Some proposedsolutions are quick and easy and other changes will happen incrementally. We share the following research-based recommendations
as first steps for making studies more accessible to and welcoming of the trans and nonbinary communities.

Adjust clinical protocols to
distinguish gender identity
from sex assigned at birth.

Involve members of thetransgender and nonbinary
communities in research.

The first step in inclusion is
expanding clinical trial protocol
eligibility criteria to include
transgender and nonbinary patients
when dosing guidance is clear
enough to ensure patient safety.
Consider setting enrollment targets
for gender-diverse people to help
create a study population thatreflects the demography ofthe disease.

The presence of trans andnonbinary study staff can help
gender-diverse people feel more
comfortable in the research setting.
And when gender-diverse staff
members, healthcare personnel, andadvisory board members help leadstudies, the trans and nonbinary
communities have a voice inresearch planningand implementation.

If dosing guidance doesn’t exist andtrans and nonbinary patients will be
excluded from a study for safety
reasons, explaining the rationale canhelp build trust within genderdiverse communities.

11 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

Communicate with sensitivity.
Pronouns. While someone might present as male or female, asking a patient
for their pronouns is the only way to know which ones that person uses.
Encourage site staff to also share their pronouns, which can foster a senseof trust and inclusivity.
Name. The patient’s chosen name may differ from their legal name. Asking
for, documenting, and using this name in conversation can make patients feel
more comfortable.
Gender identity versus sex assigned at birth. While sex assigned at birthwill often be important in a research setting, researchers can first ask
patients to provide their gender identity. This two-step approach ensuresthat both patient preference and medical history are fully understoodand recorded.
Sensitive discussions. For questions about medical history, anatomy,
gender-affirming hormone therapies, or other potentially difficult topics,
explain the impact of the requested information to patients in terms of theirsafety and care. Emphasize that responses to such questions are used toprotect their health. Some trans and nonbinary people might beuncomfortable with parts of their anatomy that don’t align with their gender
identity, so it may be helpful to conduct an anatomy inventory, in which apatient indicates through a list or diagram which parts of human anatomy
will be relevant to their care.

Upskill clinical research staff.

Practice transparency.

Where it does not already exist,
all clinical trial personnel and site
staff will benefit from foundationaland ongoing training on genderaffirming health care and inclusive
practices. When possible, engagetrans and nonbinary trainers todeliver this education.

When a patient is considering
clinical trial participation, ensuretransparency about factors that will
impact the patient, such as limited
dosing guidelines. As with any
study, clinical research staff shouldtake time to explain the procedures,provide a clear rationale for the
study, and present the associatedrisks, highlighting specifically any
elements that may be impacted by
the patients’ gender identity.

Use inclusive imagery inpatient materials.
When using imagery to promote or
explain a study, represent the full
spectrum of gender: people withdifferent gender identities andexpressions, ethnicities, races,abilities, body sizes, and ages. Show
trans and nonbinary people inprofessional as well as patient roles.

Maximize accessibility forpotential patients.
Where possible, provide genderneutral (sometimes referred to as
all-gender), single occupancy
restrooms and use private clinic
intake areas where people candiscuss sensitive issues. As much as
possible, minimize the frequency ofstudy visits, particularly for patients
who are medically or surgicallytransitioning and may have an
already-busy health carevisit schedule.

Invest in long-term
relationships.
Remaining engaged with genderdiverse communities will help build
trust with both healthcare settings
and the biopharmaceutical industry.
Continued communication after andbetween trials, sharing study results
and how those results might impact
trans and nonbinary people will help
build trust long-term.

Remaining engaged with gender-diverse communities
will help build trust with both healthcare settings
and the biopharmaceutical industry.
12 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

Line in the sand
The recommendations in this report are a starting point for change. We acknowledge, however, the existence of limitations. For
example, some trials may not be fully inclusive in the shorter term while further data about dosing practices and the impact on
the safety profile of the drug in patients receiving gender-affirming hormone therapies is determined. As an industry, we’ll also
to adjust how study and clinic technology systems are built to enable differentiation between gender identity and sex assigned
at birth. This will enable more proactive identification of potential transgender and nonbinary study participants.

To make studies truly inclusive,
additional research on
investigational drug dosing
guidelines and potential druginteractions is required. Just as
important in terms of adoption,clear guidance from regulatory
authorities is often a catalyst forchange. Because drug development
is tightly regulated, developers
necessarily rely on standards set by
the FDA, the EMA, and similar
bodies. So, clear and specificregulatory guidance and industry
best practices can facilitatebiopharmaceutical companies andtheir partners in driving consistent,
significant change.

And yet that change can happen.
Current medical science relies on
the distinct categories of male andfemale, but gender identity is much
more nuanced than simple binaries.
Drug developers encounter nuanceand complexity every day in theirwork. Every day, our industry iscreating and investigating medicines
made for diverse people in diverse
bodies. Trans and nonbinary people
are part of that diversity and part of
the real-world population our
medicines serve. Increasing genderinclusivity will be challenging andvaluable work that we should takeon with sensitivity, empathy, andprofessional rigor.

Trans and nonbinary people are part of that diversity andpart of the real-world population our medicines serve.
13 | DISCUSSIONS ON DIVERSITY: GENDER IDENTITY

We’re always available for a conversation.

Parexel International Corporation
2520 Meridian Pkwy, Durham, NC 27713, USA+1 919 544-3170
Offices across Europe, Asia, and the Americas
www.parexel.com© 2023 Parexel International (MA) Corporation.