Decentralizing

research
How reducing patient burden

improves trial diversity

Introduction
In 1976, the National Commission for the Protection of
Human Subjects of Biomedical and Behavioral Research
met for four days to map out the future of medical research.1
They were asked to identify and create guidelines for basic
ethical principles that should underpin biomedical and
behavioral research involving human participants.

The resulting document is known as the
Belmont Report, and it spells out three main
tenets that serve as the foundation for clinical
research to this day:1
• Respect for persons, including autonomy
and informed consent
• Beneficence, which refers to maximizing
benefits and minimizing risk
• Justice, or the fair distribution of costs and
benefits to potential research participants
These principles have held for decades. But
as we look at the current lack of diversity in
clinical trials, it begs the question: are research
opportunities being distributed fairly? Is the
principle of distributive justice being upheld?
And can alternative clinical trial models, such as
decentralized trials, help tip the scales towards
attaining distributive justice?
This whitepaper will look closely at the current
state of diversity in clinical trials, particularly
with regard to geographic diversity. We’ll explore
whether the alternative clinical trial approaches
necessitated by the COVID-19 pandemic might
ensure that more potential research participants
have fair access to clinical trials.

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 Snapshot of diversity
in clinical trials
It’s critical that the makeup of clinical trial participants
reflects real-world populations, so that medications are
tested for all who may need them. Unfortunately, this has
not historically been the case.

It’s no secret that people of color have been and continue to

be underrepresented in clinical research. Statistics from a
panel discussion at the BIO Conference last year reveal that
racial and ethnic minorities make up 39% of the population in
the U.S., but estimated rates of clinical trial participation for
this group range from 2% to 16%. Nearly 14% of Americans
are black, but they make up less than 5% of trial participants,
and while Latinos make up 18% of the U.S. population,
they represent just 1% of clinical trial participants.2,3 And
the need for diversity goes beyond race – people living with
chronic comorbidities and pregnant women, among others,
are often excluded from clinical trials.

Also critical to maintaining diversity is ensuring that clinical

trial sites are geographically accessible to all – not just those
near an urban center. Rural populations remain largely
underrepresented in research.4 A survey about clinical trial
participation barriers revealed that the number one reason
for declining to participate in a trial is inconvenience of travel;
this response was cited by 42% of respondents.5 And, while
some efforts have been made to enroll rural populations in
medical research, these attempts have not been successful
on any broad scale.

...racial and ethnic minorities make up 39% of the

population in the U.S., but estimated rates of clinical
trial participation for this group range from 2% to 16%.
2
Research by Deloitte found that 70% of potential In addition, expanding clinical trial access to include
participants in the United States live more than two more rural areas “may increase the heterogeneity of the
hours away from the nearest study center. One6
population sample and generalizability of the research
study published in the journal Clinical Investigations findings.”4 Importantly, it would also ensure that the
took a close look at the availability of sites based on distributive justice principle of the Belmont Report
geographies throughout the United States and found would be met.
clusters around urban centers. This study confirmed
that “within a region, population density, availability
of healthcare and/or social service facilities, and
educational establishments together were strong
predictors of the number of clinical trial sites per region,
accounting for 69% of the variability seen.”4 This makes
sense – the number of clinical trial sites increases when
healthcare facilities are available, but there may be other
factors at play as well. For example, sponsors may prefer
recruiting for trials in urban areas where they can reach
many people quickly, where patients can travel to a site
easily, and where populations tend to be more diverse.4

…expanding clinical trial access to include more

rural areas “may increase the heterogeneity of
the population sample and generalizability of
the research findings.”

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Decreasing patient burden
In November 2020, the FDA released its official
guidance for industry on “Enhancing the Diversity of
Clinical Trial Populations – Eligibility Criteria, Enrollment
Practices, and Trial Designs.”7 This includes guidelines
to ensure access to trials for all, and focuses on ensuring
that patient burden remains as low as possible.
Some suggestions for decreasing patient burden
include: designing trials to require minimal travel (with
appropriate monitoring in place); ensuring appropriate
financial reimbursement for time and travel; leveraging
digital health tools for real-time data collection; and
limiting the number of site visits needed. This notion
is also echoed in the 21st Century Cures Act (often
known as the Cures Act), which aims to accelerate
medical innovation to bring new advances to the
patients who need them faster and more efficiently.
These calls to push medical research forward while
keeping patient burden low became even more
important in 2020, when the COVID-19 pandemic
caused more than 1,000 clinical trials for non-
COVID-19 conditions to delay their start or to pause. 8
In fact, in an April 2020 survey from Medidata of more
than 1,000 sites, 69% of respondents said lockdown
measures impacted their ability to conduct ongoing
trials, and 78% said COVID-19 affected new trial
starts.9 Many of these trials were forced to add virtual
elements to their traditional trial approaches. While
many could not go fully virtual due to the need to
collect samples at specific milestones and check on
patients in person, folding in technology reduced
patient burden, keeping patients safer and allowing
some trials to get back on track.
When a trial is flexible in this way, including both
elements of virtual trials and traditional trials and
keeping patient burden low, it is referred to as a
“decentralized trial.” As defined by the Clinical Trials
Transformation Initiative, decentralized trials are
those “executed through telemedicine and mobile/
local healthcare providers.”10 With a decentralized
trial, while technology is key, it’s also critical that
any necessary in-person aspects can happen locally,
removing the need to travel to a particular site. With
their flexible approach, these types of trials invite
many more patients to the table, and get researchers
ever closer to fully achieving the Belmont Report’s
principle of distributive justice.
…these calls to push medical
research forward while
keeping patient burden
low became even more
important in 2020.
4
Weighing the benefits
of decentralized trials
As the number of decentralized trials increases, it is important
to take a close look at the potential benefits and drawbacks of
this newer approach. As mentioned, decentralization improves
diversity in trials. Because recruitment can come from a
larger pool of patients, and taking part in a decentralized
trial requires less time and schedule rearrangements on the
patient’s part, trials become more open to those in rural areas
and to those with jobs or life circumstances that do not grant
them a flexible schedule.

Much of the current literature is optimistic about

decentralized trials, and given the potential to expand
participation – that’s for good reason. Here are a few
additional benefits of decentralized trials:

Improved patient experience

Participation in traditional clinical trials can be challenging. Obstacles can include multiple visits
to clinical trial sites over extended periods of time. Technologies like telemedicine simulate the
kind of face-to-face interactions that help build trust between patient and provider and lower
the burden on the patients. Decentralized trials also improve the patient experience by making
necessary in-person visits local and adding in digital measurement tools.

Lower barriers to recruitment

Clinical trial recruitment is difficult. In fact, 80% of clinical trials are delayed or closed due
to recruitment challenges.11 The process typically includes a patient seeing an email or an
advertisement, taking a prescreener online, then visiting the site to determine eligibility and
potentially enroll. By moving some of the discussions about eligibility and informed consent
online, it becomes less challenging for researchers to fill a study. Perhaps more importantly,
however, if a study is largely virtual, location becomes less of an issue. Clinical recruitment
companies can cast a wider geographical net, speeding up the recruitment process overall –
and contributing to accelerations in the development of new therapies.

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Increased patient retention and lower drop-out
rates
Typically, 18% of patients who are randomized into a trial drop out.12 Some reasons cited
– family issues, fear and anxiety, condition not improving, side effects, and so on – are
external and difficult to prevent. Others, however, can certainly be addressed through
a decentralized trial model. These include inconvenient location, schedule conflicts,
physically unable, and forgetting visits.12

Higher data quality

Decentralized trials often require patients to leverage digital technologies to track their
health, and this allows for more real-time data collection than traditional trials. In addition,
because patient populations will be more diverse, data is more generalizable.

Improved long-term follow-up

When the patient’s experience is positive, they’re more likely to stay in touch for long-term
follow-up. And, when it’s as easy as checking in on a video conference call, the likelihood of
losing patients to follow-up is lower.

Better resilience in case of an emergency

The COVID-19 pandemic has laid bare the need to ensure that medical research can
continue in the face of an emergency. With their virtual elements and the flexibility to
become more virtual as needed, decentralized trials provide reassurance that even if
something catastrophic happens, the trial is likely to be able to continue.

Optimized efficiencies in order to run trials faster

Quicker recruitment, more diverse patient population, ease of virtual appointments,
and improved data quality all boil down to faster clinical trials. These efficiencies allow
researchers to see more patients and gather data more quickly, effectively accelerating
their research so that the therapies they’re developing can be brought to market sooner.

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Drawbacks of
decentralized trials
While there is a long list of benefits to the flexible approach of a
decentralized trial, it’s important for researchers to also consider
any potential negative aspects before selecting any particular
approach to conducting their clinical trials. Here are a few
drawbacks of making the move to decentralized trials.

Steep learning curve

It can’t be denied that decentralized or fully virtual trials are very different
from how research has been conducted traditionally. Study teams need to be
trained on telework, network access including electronic health records, and
patient privacy (such as turning off smart speakers at home). Site staff is also
responsible for setting expectations for their patients, and ensuring all are
comfortable with the digital aspects of the trial.

Therapy and disease limitations

The technical requirements for conducting trials in a decentralized way (such
as remote monitoring) can make it difficult or infeasible to execute when
studying certain therapies or working with patients with particular illnesses.13

Lack of personal touch

Fully virtual or “siteless” trials may leave patients feeling like they have no one
to guide them. Healthcare decisions are important and research has shown
that the human touch is critical to ensuring patients feel confident with
their decisions.14 Even with a decentralized model that includes some local
in-person visits, researchers will need to focus on ensuring that patients are
feeling fully informed and supported throughout the clinical trial process.
Telemedicine can go far in building trust with patients without necessitating
additional in-person interactions.

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Considerations for
going decentralized
For sponsors considering decentralizing their clinical trials,
it’s important to be fully prepared for the new approach.
There are many aspects that need to be thought through,
including:15

Patient education
Even if a researcher is speaking with patients via video or a local physician is
meeting with the them in-person, patients need to be fully informed about
the trial, including the purpose, procedures, and what to expect. When trials
are decentralized, this may mean creating a repository of information online
that patients can access from anywhere, or sending documents to their home.
Regardless of the method, remember the goal: the patient should feel as “in
the know” as they would during a traditional clinical trial.

Broad recruitment
As geographical parameters widen in decentralized trials, so too does the
scope of recruitment. Many recruitment tactics, like digital marketing
and advocacy partnerships, will still hold – but hyperlocal tactics such as
newspaper and radio ads are likely not appropriate for decentralized trials.
Broadening geotargeting on social media and paid search can help expand
reach in a way that controls for volume and cost.

Remote consenting and enrollment

processes
Without physical sites for patients to go to, eConsent is the substitute for
obtaining digital signatures as part of the informed consent process. Of note,
there is currently limited established regulatory guidance around eConsent,
but this is likely to change as more trials add virtual components.16

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Centralized monitoring
Even decentralized trials need data to feed into a single place to be documented
and evaluated. Centralized monitoring reveals trends in the clinical data, and
helps sponsors keep an eye on quality and risk indicators so that they can take
appropriate action if needed.

Telemedicine visits
If decentralizing, a sponsor or site needs to provide HIPAA-compliant telemedicine
visits to their patients. There are many established platforms that offer this service.
Even with the right program in place, however, establishing a positive patient-
provider relationship online can be difficult. Staff should be trained to ensure
positive outcomes within a digital environment; training should include specific
telehealth terminology and communication skills, which can help providers read a
patient’s physical appearance and body language.

Home healthcare solutions

If a trial requires in-person components, consider hiring home healthcare staff to
visit patients in their homes to examine them, distribute the study drug, or monitor
certain measurements. Think through how to link the home healthcare providers
with a centralized monitoring system so that the principal investigator and sponsor
are aware of progress or any changes that need to be made.

Local lab draws

Decentralized trials often require patients to visit local labs to provide samples.
Many labs partner on various aspects of clinical trials, from recruitment to
execution. Speak clearly with the patient about what to expect at the lab and once
again, ensure results of any tests are shared to a centralized monitoring system.

Direct-to-patient investigational product

shipments
For some trials, it will be appropriate to ship the study drug to each participant or a
named responsible person, such as a relative or a home care nurse. It’s critical that
the study drug maintain its integrity during shipping, so appropriate temperature
control, packaging, and monitoring should be in place. Documentation is especially
important here as some studies include chain of custody requirements and
temperature deviation verification.

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Conclusion
Medical research cannot move forward without volunteers to take part. But, the
way that trials have traditionally been run excludes large swaths of people, including
people of color and those in rural communities. One way that researchers can ensure
the Belmont Report principle of “fair distribution of cost and benefits to potential
research participants” is to lower the burden on individuals taking part in trials. The
COVID-19 pandemic has forced many researchers to move toward decentralized
trials, and it's clear that the benefits of adding virtual and local in-person elements to
trials will go far to reduce patient burden and tackle the issue of distributive justice.
Ensuring that everyone has the option to take part in a clinical trial – including those
who may live far from a health center – will lead to stronger data and ultimately,
accelerated research.

To learn more about Antidote and

our work, please get in touch
www.antidote.me | 1 (888) 509 1308 | hello@antidote.me

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1
https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html

2
https://medcitynews.com/2019/07/as-precision-medicine-grows-so-does-the-
importance-of-clinical-trial-diversity/?rf=1

3
https://www.census.gov/quickfacts/fact/table/US/PST045218

4
https://www.openaccessjournals.com/articles/geographic-distribution-of-
clinical-trials-may-lead-to-inequities-in-access.pdf

5
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327530/#!po=2.27273

6
https://www2.deloitte.com/us/en/insights/industry/life-sciences/digital-
research-and-development-clinical-strategy.html

7
https://www.fda.gov/media/127712/download

8
https://www.clinicaltrialsarena.com/comment/us-clinical-trials-covid-19/

9
https://www.medidata.com/wp-content/uploads/2020/05/COVID19-
Response4.0_Clinical-Trials_2020504_v3.pdf

10
https://www.healthaffairs.org/do/10.1377/hblog20200702.963588/full/

11
https://www.biopharmadive.com/spons/decentralized-clinical-trials-are-we-
ready-to-make-the-leap/546591/

12
https://forteresearch.com/news/infographic/infographic-retention-in-clinical-
trials-keeping-patients-on-protocols/

13
https://www.healthaffairs.org/do/10.1377/hblog20200702.963588/full/

14
https://www.antidote.me/tech-human-touch-whitepaper

15
https://www.rhoworld.com/covid-19-resource-center/conducting-clinical-
trials-during-the-pandemic/

16
https://www.transceleratebiopharmainc.com/assets/econsent-solutions/
what-is-econsent/#:~:text=Empowers%20patients%20to%20make%20
informed,and%20a%20fully%20electronic%20system