In this technocracy dominated era, there's no dearth of technological approaches to improve clinical trial (CT) participation. Ranging from alert systems linked to electronic health records (1) to online registries (2, 3,
4), the usual technology-based suspects have made their appearance on
the scene to no avail. For e.g., available free to anyone online,
ResearchMatch allows any US resident to register as a potential CT
participant (volunteer). Hosted at Vanderbilt University and funded by
the NIH, this registry launched in December 2008. Yet >7 years on,
its name recognition is limited and <100000 volunteers have signed up
(2).
Obviously,
core of the problem requires a human, not technological, touch.
Meantime, the general population gains the bulk of its knowledge about
CTs from entertainment fare online or on TV and from news (5, 6, 7, 8).
Obviously such sources are more likely to fuel and sustain
misconceptions rather than anything remotely close to the truth about
CTs. Essentially, the current CT ecosystem woefully under-utilizes two
of its foundational pillars,
2) Current and previous CT participants, i.e., potential Patient Advocates.
Even more inexplicably, pertinent questions relating to the CT process remain unanswered
- What's the difference between healthcare providers who either do or don't participate in CTs, and between those who either do or don't refer patients to CTs?
- What are the recruiting strategies used by successful CTs (11, 12, 13)?
- Why don't organizers of successful CTs routinely record and report their recruiting strategies? Clearly trial funders should mandate their doing so.
- What level of engagement remains with CT participants after a trial's over? Do trial organizers and their staff stay in touch with them? While volunteers are enrolled in a trial, which can be for several months to even years, do trial organizers develop a rapport with at least their most enthusiastic participants, and teach and encourage them to advocate and recruit newer volunteers on their behalf within their families and communities (14, 15)? Given the current state of affairs, clearly not and yet wouldn't doing so set up a virtuous positively reinforcing cycle leading to cumulatively increasing CT participants? Instead, why is the system set up to recruit and forget once the trial's over? Isn't this an egregious example of re-inventing the wheel every time?
~70
years since the 1st double-blind, placebo-controlled randomized CT and
with >210,000 ongoing registered CTs across the US and 193 other
countries (see figure below from 16),
it's scarcely believable but sadly true that such basic issues aren't
well-studied nor their lessons freely available for others' benefit (17,
18).
Upon
reflection, it's only to be expected that an inherently top-down and
paternalistic enterprise like human biomedical research would
under-utilize Patient Advocates. After all so insular is it that its very basics such as research ethics and regulatory oversight have been developed without seeking and incorporating the input of research volunteers (19), who are more frequently described condescendingly as subjects.
Even peer-reviewed literature about woefully lacking CT participation
rates is dominated by the voices of biomedical research aficionados.
Where are the voices of CT participants? Why don't medical and
scientific journals report their perspective, about their experiences
and suggestions in their own words? Imbalance couldn't get starker than
this (20). When was the last time the US FDA or the NIH convened
meetings or town halls specifically inviting volunteer input into the CT
process? Never. The current CT world is strikingly insular (21, 22).
'Findings concur with previous research suggesting that CT investigators rarely communicate about clinical research outside of specific, study-based recruitment messages, which are often only provided to current patients already familiar with the medical institution...Findings from the current study, however, show that CT teams rarely promote CT research outside of the medical setting or reach out to community organizations to serve as an important conduit between the medical institution ß and hard-to-reach populations...Although investigators rely heavily on local physicians to recruit patients into their studies, there may be limited communication between the investigators and local physicians [37] and between these local doctors and their patients [28].'
(8).
The
funders and fund recipients, i.e., clinical researchers and their
support staff working largely in academic medical centers, currently
control the process. They hold endless rounds of meetings and write
exhaustive white papers and reports filled with earnest recommendations.
These current CT stakeholders haven't yet thought to expand their fold
and bring into it the ones whose voices perhaps matter the most in CT participation and logistics, patients and volunteers who've participated in CTs, i.e., Patient Advocates.
We all know new drugs and therapies can't get approved unless robustly
tested on large pools of volunteers, and yet those same volunteers, the
very heart of human biomedical research, have no say in how the process
could be structured so their ranks stay filled, not depleted.
What Factors Deter CT Participation And How They Could Be Mitigated
Obvious
ones are fears about unapproved medications and procedures, i.e., that
one could be used as a 'guinea pig', as well as fears of side-effects,
and that one could get a placebo instead of Rx due to randomization.
Given such fears are likely pervasive among the population at large (23, 24, 25,
26), who could be more persuasive in convincing others to participate
in CTs than those who've done so themselves? If previous trial
participants aren't doing so, maybe there's something inherently
discouraging about the process that urgently needs to be overhauled?
While the medical and scientific aspects of CTs are rightfully the
purview of clinical researchers and scientists, and should remain so,
these patient-centric aspects are areas where Patient Advocates could help reshape the process to encourage others.
Studies
also suggest local community-based sources of CT information are seen
as more trustworthy. These include local doctors, TV and community
health centers (7). As well, informal family and community networks,
i.e., family and friends, and local church and faith-based organizations
(26).
Cancer Clinical Trial (CT) Participation Rates Are High In Children Regardless of Race/Ethnicity But Very Low Among Adults. What Accounts For Such A Difference?
Poorly
envisaged top-down policies often lack mechanisms to enforce their
recommendations. In US biomedical research, one of the most prominent
examples is the 1993 NIH Revitalization Act that mandates inclusion of
racial and ethnic minorities in federally funded biomedical research (27).
23 years on, African Americans and Hispanics represent 12% and 16%,
respectively, of the US population and yet constitute only 5% and 1% of
CT participants (28) while whites are over-represented (29). Why is this so? Among US CT volunteers, blacks are supposed to mistrust medical research, and language and culture are supposed to be barriers to Hispanic participation while implicit bias among clinical researchers is supposed
to disfavor minority participation in CTs. However, a crucial piece of
data unerringly rebuts these oft-repeated myths because there's more
than adequate participation among children regardless of race/ethnicity compared to dismal rates among adults.
In the US, only 3 to 5% of ~10 million adults with cancer participate in CTs (30).
However, CT enrollment among <15 years old is anything but dismal.
In the US, 60% of cancer patients aged <15 years are enrolled in CTs
(31). That's not all. Proportion of minority pediatric cancer patients
enrolled in cancer CTs (~10% blacks, ~12% Hispanic) ~matches their
proportion in the population (32). This means neither do pediatric
minorities systematically lack access to health research nor face
systemic bias against CT enrollment. How to explain this huge difference
between children and adult CT enrollment rates? What's different about
the pediatric CT recruitment process? Undoubtedly, applying what works
in recruiting children to CTs would hugely improve adult enrollment
rates.
Crux Of The Problem: Huge Gap Between Eligible And Actual Adult Clinical Trial (CT) Participants
Real
gap in adult CT enrollment is ~10X. For e.g., in the US, ~20% of cancer
patients are typically eligible to participate (33, 34) but only 3 to 5% of them do so (30).
This huge gap between eligible and actual participants is the critical
problem needing to be solved. Weakest link in the chain? Extremely poor
inclusion of referring physicians and Patient Advocates into the
CT recruitment process, i.e., we're back to square one, the need to
expand the fold of current CT stakeholders to include patients and
volunteers, and their physicians, and seek their input in improving CT participation and logistics.
One approach could be to have CT participants access trial-related
procedures and services closer to their home rather than exclusively at
academic CT sites, which are often far from their homes.
Clinical Trial (CT) Location Matters Hugely To CT Participants
Travel distance to and lack of transportation to and from the trial site are major barriers in CT participation (35, 36, 37).
Even in the US, arguably the wealthiest country in the world and
unquestionable global CT leader, many if not most CT volunteers need to
drive >1 hour each way to reach a CT site (see figure below from 38).
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https://www.quora.com/How-can-clinical-trial-enrollment-be-increased/answer/Tirumalai-Kamala
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