5 Principles (5P’s) of Advancing Inclusive Research (AIR)
March 7, 2025
Shalini Hede, PharmD
1
The integration of inclusive research principles in clinical development is increasingly imperative. We propose to derive a comprehensive and unified set of principles that address inclusive research gaps and are adopted by all levels of the Roche organization across the clinical development timeline.
Problem statement
Despite significant pressure from Regulatory agencies to ensure the inclusion of representative patient cohorts in drug development initiatives, biotechnology companies continue to conduct clinical trials that do not fully represent diverse patient populations.
Medications are not thoroughly examined for safety, efficacy, and accessibility across all demographic groups.
Outcomes of clinical trials for marginalized populations remain uncertain and fail to provide valid real-world evidence.
Proposed solution
WHY: At Roche, we strive to ensure that
all populations are represented in biopharma research and development by Advancing Inclusive Research (AIR).
2
The 5 Principles (5Ps) Framework
The 5P framework was derived from simulating several studies in
a pharmaceutical late-stage portfolio where components formed the basis
for a data-informed framework to measure, standardize, and systematically define inclusive research.
5Ps can be considered a conceptual structure for a measurable,
transparent definition of clinical trial representativeness that
can function within organizational constraints.
3
The 5Ps of Advancing Inclusive Research (AIR)
eCRF=electronic case report forms with self-reported race / ethnicity categories applicable globally; SDOH=social determinants of health; SOGI=sexual orientation and gender identity
WHO?
Population Health�(Biological/�Genetic/ Demographic ) Considerations
1
WHERE?
Data-Informed Country & Site Selection to reach representative
patient cohorts
a. Geographical Proportionality Trial Enrollment (Region)
b. Accurate Demographic Representation (Country)
c. Representative real-world population (Site selection)
2
WHAT?
End-to-End
Inclusive
Trial Design (User-informed
and Data-Driven)
3
HOW?
Maximize Patient
Access to Trials
5
WHY ME?
Patient- Reported Data Collection Standards
(incl. eCRF,
SDOH, SOGI)
4
4
Population Health Considerations WHO are patients with the disease?
WHO
PRINCIPLE 1
WHERE
WHAT?
WHY ME?
H0W?
Population Science descriptors (via literature reviews) translated and captured in HE&PS DAPA reports (#20) across Oncology, Neurology, Neuroimmunology, Ophthalmology, Respiratory, and Cardio-metabolic-renal disease
Biological & Genetics Considerations:
Demographics Considerations:
5
Data-Informed Country & Site Selection
WHERE to reach representative patient cohorts
WHO
PRINCIPLE 2
WHERE
WHAT?
WHY ME?
H0W?
a.
Geographical Proportionality
Trial Enrollment
(Region)
b.
Enable Access and Commercialization (Country)
c.
Representative real-world population
(Site)
Enrollment Goal Setting Guidance, DAP Template, AIR Calculator, R-Index (links)
6
End-to-End Inclusive Trial Design
WHAT considerations to include in protocol design
WHO
PRINCIPLE 3
WHERE
WHAT?
WHY ME?
H0W?
Artificial intelligence algorithms combined with real-world data can potentially improve several aspects of clinical trials including:
Data-driven
Include input from providers, patient/patient advocacy groups, and investigators on the study trial design.
New Roche PDG mandate: New protocols due to be finalised Q1 ‘24 onwards are developed with
consideration for the patient.
User Informed
ASCO evidence-based recommendations that laboratory tests should be used as exclusion criteria only when necessary. (link)
FDA has also developed a series of guidelines for eligibility criteria, however these are not standards and have not been widely implemented by many companies.
7
Patient-Reported Data Collection Standards
(eg. eCRF, SOGI)
WHO
PRINCIPLE 4
WHERE
WHAT?
WHY ME?
H0W?
Current Roche eCRF Race or Ethnicity Categories | Proposed Roche eCRF Race or Ethnicity Categories | Race or Ethnicity eCRF Sub-categories | Directive No 15 (1997) | Directive No 15 (2024) |
HISPANIC OR LATINO | HISPANIC OR LATINO | Mexican | Hispanic or Latino | Hispanic or Latino |
Puerto Rican | ||||
Salvadoran | ||||
Cuban | ||||
Dominican | ||||
Guatemalan | ||||
Other Hispanic or Latino culture or origin | ||||
ALASKA NATIVE OR AMERICAN INDIAN | ALASKA NATIVE OR AMERICAN INDIAN | North American Indian Or Alaska Native | American Indian or Alaska Native | American Indian or Alaska Native |
Central American Indian | ||||
South American Indian | ||||
Other Indigenous Not Listed | ||||
ASIAN | ASIAN | Chinese | Asian | Asian |
Filipino | ||||
Japanese | ||||
Korean | ||||
South Asian | ||||
Vietnamese | ||||
Other Asian Not Listed | ||||
BLACK | BLACK | African American | Black or African American | Black or African American |
African Caribbean | ||||
Black African | ||||
Other Black Identity Not Listed | ||||
INDIGENOUS AUSTRALIAN OR PACIFIC ISLANDER | INDIGENOUS AUSTRALIAN OR PACIFIC ISLANDER | Aboriginal Or Torres Strait Islander | Native Hawaiian or Other Pacific Islander | Native Hawaiian or Other Pacific Islander |
Maori | ||||
Native Hawaiian | ||||
Other Pacific Islander Not Listed | ||||
MIDDLE EASTERN, NORTH AFRICAN, OR WHITE | MIDDLE EASTERN OR NORTH AFRICAN | Middle Eastern | White | Middle Eastern or North African |
North African | ||||
WHITE | White | White | White |
1. What is your sexual orientation?
2. What is your current gender identity?
Optional SOGI Questionnaire for
Clinical Research Survey
Reconciliation of eCRF to FDA/OMB Race Categories
8
Patient-Reported Data Collection Standards
(cont. SDOH Questionnaire)
WHO
PRINCIPLE 4
WHERE
WHAT?
WHY ME?
H0W?
Education
What is your level of education/schooling?
[ ] Elementary School
[ ] Middle School
[ ] Some High School
[ ] Graduated from High School
[ ] Some College
[ ] Graduated from College
[ ] Post-Graduate
Employment Status
Before your diagnosis, what was your employment status?
[ ] Full-time Employed
[ ] Part-time Employed
[ ] Self-employed (either full-time or part-time)
[ ] Retired
[ ] Not employed
Health Insurance Status
What type of health insurance do you have, if any. Please select one:
[ ] Private/Commercial
[ ] Medicare
[ ] Medicaid
[ ] Veteran Affairs (VA) Health Plan
[ ] Other
[ ] I do not have a health insurance
Income Status
What is your annual household income?
[ ] E< $15,000
[ ] $15,000 - $34,999
[ ] $35,000 - $49,999
[ ] $50,000 - $74,999
[ ] $75,000- $99,999
[ ] $100,000 - $149,999
[ ] >$150,000
Marital Status
What is your marital status?
[ ] Single (never married)
[ ] Married (including common law)
[ ] Separated
[ ] Divorced
[ ] Widowed
[ ] Domestic Partnership [ ] (same sex, opposite sex or unregistered)
Zip Code of Home Residence
What is the zip code of your home residence?
9
Maximize Patient Access to trials
WHO
PRINCIPLE 5
WHERE
WHAT?
WHY ME?
HOW?
Partnerships to enable access during trials ie. transportation
A fundamental and ethical aspect of study placement and
access is Roche will only conduct trials in countries where
a sustainable path to regulatory and access approval exists.
Post-trial access/reimbursement
programs
Demonstrating
Trustworthiness
10
Maximize Patient Access to trials
1.
P5
Enhanced Patient Support Services (EPSS)
11
Where are the patients most affected by multiple myeloma?
121.9-194.0
60.4-121.9
36.5-60.4
22.5-36.5
4.3-22.5
Crude rate per 100,000
Principle 2
Data-driven country and site selection
Incidence per 100,000 people
Who are the patients most affected by multiple myeloma?
Principle 1
Biological/genetic and population health considerations
Patient demographics
Patient risk factors
Region | Number of cases | % |
Africa | 6882 | 4 |
Americas | 52,190 | 28 |
United States | 4779 | 3 |
East Mediterranean | 7309 | 4 |
Europe | 53,889 | 29 |
Southeast Asia | 23,117 | 12 |
Western Pacific | 44,541 | 24 |
Race | |
White | 74% |
Black | 21% |
Asian/Pacific Islander | 3% |
American Indian/Alaska Native | 0.7% |
Ethnicity | |
Non-Hispanic | 91% |
Hispanic | 9% |
Age | |
<40 | 1% |
40-64 | 34% |
≥65 | 65% |
Sex at birth | |
Male | 55% |
Female | 45% |
Race | 2-3x higher incidence in African Americas than other race/ethnic origins |
Gender | 1.5x higher in men than women |
Age | Older age of diagnosis, median age of diagnosis 69 years old Younger median age of diagnosis among Black patients compared to White patients |
Family history | 2-4x risk 1st degree relative with MM |
Environmental exposures | Post 9/11 workers, exposure to agent orange in Vietnam War, pesticides and chemicals |
What will the multiple myeloma trial design look like?
Principle 3
User informed end-to-end inclusive trial design
Why are we focusing on these patients?
Principle 4
Patient-reported demographic identification
How will patients access trials and treatment?
Principle 5
Enabling access to trials
12
Where are the patients most affected by breast cancer?
Principle 2
Data-driven country and site selection
Overall incidence per 100,000 people
71.1-105.4
52.2-71.1
39.2-52.2
27.8-39.2
4.6-27.8
Crude rate per 100,000
Prevalence rate, %
Prevalence of HR+ HER2- breast cancer
Clinical trial site locations
Who are the patients most affected by breast cancer?
Principle 1
Biological/genetic and population health considerations
Patient demographics
What will the breast cancer trial design look like?
Principle 3
User informed end-to-end inclusive trial design
Why are we focusing on these patients?
Principle 4
Patient-reported demographic identification
How will patients access trials and treatment?
Principle 5
Enabling access to trials
| US Target | Number on study | Percent on study |
Race | | | |
American Indian/Alaska Native | 0.4% | 2 | 1.4% |
Black or African American | 11.1% | 15 | 10.4% |
Asian | 5.7% | 12 | 8.3% |
Native Hawaiian/Pacific Islander | 0 | 0 | |
White | 82.9% | 101 | 70.1% |
Multiple (eg, Black and Asian) | | 1 | 0.7% |
Not reported/unknown | | 13 | 9.0% |
Ethnicity | | | |
Non Hispanic White | 91.1% | 115 | 79.9% |
Hispanic any race | 8.9% | 20 | 13.9% |
Not reported/unknown | | 9 | 6.3% |
North America |
United States |
Europe |
Germany |
Greece |
Italy |
Spain |
Turkey |
United Kingdom |
Asia |
Japan |
Republic of Korea |
Singapore |
Taiwan |
South America |
Argentina |
Africa |
South Africa |
13
Where are the patients most affected by COPD?
Principle 2
Data-driven country and site selection
COPD prevalence, 2021
Age standardized incidence per 100,000 people
South Asia
North America
East Asia
Latin America
Sub-Saharan Africa
Clinical site locations
What will the COPD trial design look like?
Principle 3
User informed end-to-end inclusive trial design
Why are we focusing on these patients?
Principle 4
Patient-reported demographic identification
How will patients access trials and treatment?
Principle 5
Enabling access to trials
Who are the patients most affected by COPD?
Principle 1
Biological/genetic and population health considerations
Patient risk factors
Race | Latin American / Indigenous American ancestry had multiple protective factors (PRDM15, IL6R, CYP2F2P). Risk variants established in European-ancestry cohorts, such as KCNE2, GPR126 |
Age | NHBs are more likely to develop COPD at a younger age, with less cumulative smoking |
Environmental exposures | Smoking, including secondhand smoke, global rural populations had higher COPD rates than urban populations, ambient particulate matter, household air pollution, occupational particulates, and ozone |
North America |
Canada |
United States |
South America |
Argentina |
Brazil |
Chile |
Africa |
Kenya |
South Africa |
Europe | ||||
Austria | Denmark | Hungary | Netherlands | Sweden |
Belgium | France | Israel | Poland | Switzerland |
Bulgaria | Germany | Italy | Romania | Turkey |
Czechia | Greece | Latvia | Spain | UK |
Asia Pacific | |
Australia | Republic of Korea |
China | New Zealand |
Hong Kong | Philippines |
India | Taiwan |
Japan | Thailand |
14
More variable; dependent on unique disease characteristics, and prioritization may differ across disease conditions
May be less dynamic; strategies can be less dependent on disease-specific factors
5P AIR Framework:
Interdependencies with Disease Condition
5
2
3
4
1
Population Health (Biological/Genetic/
Demographic) Considerations
Data-Driven Region, Country & Site
Selection
End-to-End Inclusive Trial Design (Data-driven & User-informed)
Patient-Reported data collection standards (eg. eCRF, SDOH, SOGI)
Enabling Access �to Trials
15
Applying 5Ps End-to-End
Population Health (Biological/Genetic/
Demographic) Considerations
Data-Driven Region, Country �& Site Selection
End-to-End Inclusive Trial Design (Data-driven and User-informed)
Patient-Reported data collection standards (eg. eCRF, SDOH, SOGI)
Enabling Access �to Trials
Pre Trial
Clinical Trial
Post Trial
Enrollment by global regions �should be proportional to the geographical burden of disease �both between and within countries
Enrollment by demographic �variables such as race, ethnicity, �age and sex should adhere to �country-specific standards
Understand country-specific operational constraints: capabilities, resource and regulatory guidelines
Guided by regulatory requirements, local demographics, disease burden for optimized representativeness �and efficiency
Established regional frameworks to benchmark to advance diverse trial enrolment on a global basis
If study targets are not met can activate resources or alternative sites for future trials
Decisions made at study level that are specific to each study
Collection of patient reported data to ensure equity and representativeness in trials (eCRF, SDOH, SOGI) to also reflect county appropriateness
Data collection should respect country and region categorizations
Modifications based on systematic vs ad hoc assessments of �available data
Modifications with the goal of removing barriers or ensuring appropriate considerations
Real world data can inform the 5Ps
Ensuring access to treatments and post-trial access programs
16
The 5Ps of Advancing Inclusive Research (AIR)
eCRF=electronic case report forms with self-reported race / ethnicity categories applicable globally; SDOH=social determinants of health; SOGI=sexual orientation and gender identity
WHO?
Population Health�(Biological/�Genetic/ Demographic ) Considerations
WHERE?
Data-Informed Country & Site Selection to reach representative
patient cohorts
a. Geographical Proportionality Trial Enrollment (Region)
b. Accurate Demographic Representation (Country)
c. Representative real-world population (Site selection)
WHAT?
End-to-End
Inclusive
Trial Design (User-informed
and Data-Driven)
WHY ME?
Patient- Reported Data Collection Standards
(incl. eCRF,
SDOH, SOGI)
HOW?
Maximize Patient
Access to Trials
1
2
3
4
5
17
Doing now what patients need next
18