Apr 4, 2019
Show Notes for Podcast Eleven of seX & whY
Host: Jeannette Wolfe
Interview with Dr. Cara Tannenbaum, Professor in the
Faculties of Medicine and Pharmacy at the Université de Montréal in
Canada, and Scientific Director of the Institute of Gender and
Health of the Canadian Institutes of Health Research
Definitions
Biological Sex- chromosomes, hormones, reproductive anatomy,
usually binary
Gender- social and cultural construct- falls on a spectrum
- For a really nice summary of current use of definitions please
see this excellent review.
- Excellent websites with tons of resources
Historically factors that limited the inclusion of women in
clinical trials.
- Belief that outside of reproductive zones, males and females
were the same
- Dogma that the female estrous cycle screwed up data and that
male animals produced “cleaner” results
- Two interesting facts: 1) Many female rodents’ entire estrous
cycle is only 4 days!; and 2) We now know that male animals also
have significant hormonal fluxes and that overall they are actually
just as variable as females- see review
- Concern after the worldwide thalidomide nightmare* and the
public backlash from the discovery of several unethical government
sponsored clinical trials, that fetuses (along with prisoners and
children) needed extra protection from the potential of unnecessary
harm by participation in a research trial. This led to regulatory
protection via the Common Rule. As any women of child-bearing age
could theoretically become pregnant, they (and ultimately
by cultural proxy all women) were essentially excluded
from most human trials and early clinical phase drug trials from
1970’s to the mid 1990’s.
- To read and an inspiring story as to why most of American was
saved from the limb-shortening horrors of thalidomide,
read here. (Essentially, FDA scientist Dr. Oldham Kelsey
refused to sign off on its application, even amidst considerable
pressure from the drug company, due to concern of inadequate
evidence.)
Interesting sex and gender differences in car crashes
- Crash dummy 101
- Historically crash dummy is
Hybrid III which is 5’9’’ 170 pounds representing an average
male
- Hybrid III female model- 5’ 110 pounds
-
Other models- used by NHTSA
- Why injury patterns may be different between men and women
- Differences in baseline anthropometric measures (like
height)
- Biomechanical differences (women more prone to whiplash due to
differences in neck muscular)
- Mechanical design (Smaller adults sit closer to steering wheel
and increase risk of lower extremity injury, and are more
vulnerable to side impact since more of their head is in front of
window)
-
NASS CDS data
- Weight annual sample of US 5000 police reported tow away
crashes
- Collects data on
- Occupant demographics (Age, sex, weight, BMI; Restraint use;
Injuries obtained (via medical records and interviews) standardized
into an abbreviated injury scale (AIS). It examines fatality and
whole body and regional injuries, on a 1-6 scale of severity
- Vehicle properties (Type, model year)
- Crash conditions (Estimated speed, mechanism of impact)
What we know from NHTSA data and
Insurance Institute for Highway Safety
- Overall, males represent about 70% of overall fatalities for
crashes
- Greatest gender differences is in 20-29 age group
- Men more likely to have alcohol involved in accident
- On average men drive about 5000-6000 miles/yr more than women
- Women more likely to work closer to home
- Crashes more likely to be low speed and to occur in more
congested areas
- If a man and a woman are both in car
- Males more likely to be driver
-
Summary of Bose study Vulnerability of female drivers
involved in motor vehicle crashes: An analysis of US population at
risk.
- Question they asked- for a comparable crash do male and female
drivers sustain similar rates of injuries.
- Examined injury outcomes in men and women using 1998-2008 NASS
CDS data set
- For a comparable crash, women had 47% percent greater chance of
being severely injured than men (had a higher risk of chest and
spine injuries)
- Of note the researchers controlled for weight and BMI
Other evidence that the clinical relevance of studying different
sized and biomechanical models in crashes is important is shown by
data obtained in 2011 after the NHTSA
changed their safety star ratings to include testing of a female
sized dummy in the front passenger seat. Many cars found their
ratings go down, for example the 2011
Sienna minivan saw its ratings for passenger frontal crashes go
from 5 star to 2 after it was shown that at 35mph that 20-40% of
female dummies were killed or seriously injured compared to the
industry average of 15%.
Underscoring the “literal” blind spots that can occur if you
don’t consider factors associated with diversity in study design, a
recent study from Georgia Tech suggested
that some of the visual recognitions systems used that are critical
for self-driving car safety may not adequately recognize dark
skinned faces showing a 5% increased chance of error in recognition
compared to that of fair skinned faces. Of note, there is a
significant lack of gender and racial diversity in the
self-driving car technology teams and in
artificial intelligence/tech research overall.
Who makes up the team influences what gets studied,
click here for a recent Lancet article and here for a
Nature Human Behavior one both showing that sex-related
outcomes are far more likely to be reported in medical research
consisting of diverse teams.
Take home points
- Including the variables of biological sex and gender in
research results in better science and has led to the discovery of
huge knowledge gaps that need to be closed if we want to optimize
the care of all of our patients
- Our historical medical research model has been predominately
based on the study of male animals. There are multiple reasons for
this including a true belief that: outside our reproductive zones
that men are women are exactly the same; using males animal
produces cleaner data; and including women of child bearing age in
clinical research trials exposes women to unnecessary risks without
significant benefit. We now know that all these reasons are
fundamentally flawed. Every cell has a sex and the
differences between men and women outside their
reproductive zones are often quite clinically important. Studying
males and females side by side helps us to optimize the care of
both sexes. In women it allows us to double check that therapies
that were originally developed in men actually work in women and
have the same benefit/side effects profiles. And for men, in
instances when it is discovered that women have more favorably
outcomes, it allows us to go back to the lab, figure out why there
is a difference and then to use that knowledge to develop new
therapies to help men.
- To move the scientific community and its deeply ingrained
culture to a new model that incorporates the variables of sex and
gender will require a comprehensive multi-targeted approach. Key
considerations include- engagement, education, skill building
around research methodology and analysis, mentoring and funding
incentivization. Of note Institutional review boards, journal
editors, grant reviewers and conferences directors have great power
to jump start this transition by including an expectation of sex
and/or gender inclusion in submission requirements.
- As we live in an ever increasingly complex world, now more than
ever, it is essential that we pay attention to who is actually
doing the research and developing new technologies. A diverse world
requires diverse teams.
Next month we will look at the science pipeline from bench to
bedside to identify opportunities to do better science.