Summary
Evidence Report/Technology Assessment: Number 122
Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.
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Introduction / Methods / Literature Search Methods / Results / Discussion / Recommendations and Future Research / Availability of Full Report / References
Authors: Ford JG, Howerton MW, Bolen S, Gary TL, Lai GY, Tilburt J, Gibbons MC,
Baffi C, Wilson RF, Feuerstein CJ, Tanpitukpongse P, Powe NR, Bass EB.
Introduction
The burden of cancer falls disproportionately
upon the medically underserved, and research
studies are essential to improving health care in
general, including for medically underserved
populations. Clinical trials are used to evaluate
efficacious prevention and treatment
interventions; however, studies often fail to recruit
the planned number of participants.1 Trials often
do not include an adequately diverse population
to ensure broad generalizability of results.2
Recent
studies of patients enrolled in cancer treatment
trials sponsored by the National Cancer Institute
(NCI) have demonstrated that the following
populations are underrepresented in terms of their
participation in cancer treatment trials: the
elderly, those of low socio-economic status, those
living in rural areas and Latino/Hispanic, Asian/Pacific Islander and American Indian/Alaska
native men and women, as well as African-American men.3,4
Since the 1980s cancer
prevention trials have been conducted with
participants at highest risk for disease to reduce
the cancer burden, and as in treatment trials,
adequate representation of underserved
populations in prevention trials is desirable.
Questions remain regarding the appropriate level
of inclusion, i.e., whether it might depend on the
prevalence of the condition/disease studied in the
overall population. This issue has not been
addressed adequately in the literature. Moreover,
there is substantial uncertainty about what are
important barriers and promoters of recruitment
of underrepresented populations, and what
evidence-based interventions would address them.
At the request of and with the financial
support of NCI, AHRQ commissioned a
systematic review of the existing evidence on the
recruitment of underrepresented populations into
cancer clinical trials, to be performed by the Johns
Hopkins University EPC. Specifically, the EPC
investigators were asked to consider six key
questions:
- Key Question 1: What methods (e.g., survey
studies, focus groups) have been used to
study strategies to recruit underrepresented
populations into cancer prevention and
treatment trials? We defined
underrepresented populations as including
the elderly, adolescents, those of low
socioeconomic status, those living in rural
areas, African Americans, Hispanics/Latinos,
Asian Americans, and American Indians.
- Key Question 2: What measures of success
(e.g., proportional representation relative to
the U.S. population; proportional
representation relative to incidence in a
specified population) have been used to
evaluate the efficacy and/or effectiveness of
strategies for recruitment of
underrepresented populations into cancer
prevention and treatment trials?
- Key Questions 3 and 4: Which recruitment
strategies (e.g., media appeals, incentives,
etc.) have been shown to be efficacious
and/or effective in increasing participation of
underrepresented populations in cancer treatment and
prevention trials?
- Key Question 5: What are the documented barriers to
and promoters of participation of underrepresented
populations in cancer prevention and treatment trials?
Examples of potential barriers include access, knowledge,
attitudes, eligibility, fatalism, religiosity/spirituality and
exclusions by design. Examples of potential promoters
include attitudes, altruism, advanced disease, financial
incentives, and no-cost treatment.
- Key Question 5a: Do these barriers and promoters
differ by age, gender, socioeconomic status or
race/ethnicity?
- Key Question 5b: Are these barriers and promoters
modified by cultural factors?
- Key Question 6: What effects do the attitudes and
perceptions of health care providers have on the
efficacy/effectiveness of strategies for recruitment of
underrepresented populations into cancer prevention and
treatment trials? Health care providers were defined as
including any health professional or health care
organization that provides health services to patients.
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Methods
We developed a conceptual framework to guide our analysis,
based on the factors leading to the acceptance or refusal of
participation in a cancer clinical trial. This framework was
derived from a conceptual model developed previously by two
members of the EPC team.4 The premise for the framework is
that in order to accept or refuse participation in a clinical trial,
one must first be aware of the availability of the trial, and have
an opportunity to participate in the trial. The opportunity to
participate in a clinical trial may present itself first, encouraging
patients to seek information about the trial. This, in turn, may
lead to the decision to accept or refuse participation in the trial.
There are multiple pathways to successful recruitment to a
clinical trial, including: (1) patients/clients receiving
information about clinical trials in general through health care
providers or their own social ties, and subsequently accepting a
specific opportunity to participate in a trial; and (2) in the
absence of prior awareness about clinical trials, patients/clients
may consider an opportunity to participate in a trial, with the
result of encouraging them to seek or receive information
regarding the trial, thereby increasing trial awareness. Key
questions 5 and 6 of this report address barriers and promoters
of awareness, opportunity, and acceptance/refusal.
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Literature Search Methods
Searching the literature included the steps of identifying
reference sources, formulating a search strategy for each source,
and executing and documenting each search.
Sources
Our comprehensive search plan included electronic and
hand searching. In March 2004, we searched the following
electronic databases: MEDLINE®, the Cochrane CENTRAL
Register of Controlled Trials (Issue 1, 2003), the Cochrane
Database of Methodology Reviews (CDMR), the Cumulative
Index of Nursing and Allied Health Literature (CINAHL®),
the Psychological Abstracts (PsycINFO), and The Campbell
Collaboration's Social, Psychological, Educational, and
Criminological Trials Register (C2-SPECTR).
Hand searching for possibly relevant citations took several
forms. First, we identified 34 journals by asking our experts
what journals were most likely to contain relevant articles. We
scanned the table of contents of each issue of these journals for
relevant citations from January 2003 through July 2004.
For the second form of hand searching, we used ProCite®, a
reference management software, to create a database of
reference material identified through an electronic search for
relevant guidelines and reviews, through discussions with
experts, and through the article review process. The principal
investigators reviewed the articles identified as being possible
review articles during the abstract review process. The
references in these review articles were searched to identify any
additional article for consideration. We also used MEDLINE®
to search articles published by selected experts known to have
interests related to our questions. Finally, we examined the
reference lists of eligible articles to identify any potentially
relevant articles (this was completed by the second reviewer as
part of the article review process).
Study Selection
Articles included in this evidence synthesis were English-language
reports of original data from published studies that
addressed one of the key questions.
Data Extraction
Pairs of reviewers assessed the study quality and abstracted
data for each eligible article. Data were entered into a relational
database.
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Results
Of the 4,436 citations retrieved by the search methods,
1,089 were eligible for abstract review and 218 of those were
eligible for article review. Only 67 of the articles were eligible
after article review. Many articles were excluded because they
did not address underrepresented populations, did not address
cancer treatment or prevention, or did not discuss recruitment
to a controlled trial. Ultimately, the EPC investigators
identified 14 articles on key question 1, 23 articles on key
question 2, five articles on key questions 3 and 4, 45 articles on
key question 5, and 10 articles on key question 6.
Key Question 1: Methods to Study Recruitment Strategies
We analyzed 14 articles to identify methods (e.g., survey
studies, focus groups) that have been used to study strategies to
recruit underrepresented populations into cancer prevention
and treatment trials. 5-18
- All 14 studies were of U.S. origin, primarily based in
community settings, and targeting patients/participants.
- The reported study designs of the 14 studies varied,
including descriptive (n=4), randomized controlled trials
(n=3), quasi-experimental (n=1), comparisons of two or
more interventions (n=2), survey (n=1), qualitative (n =
1), case study (n=1), and other (n=1).
- There was substantial variability across the studies in the
reporting of demographic variables such as age, gender,
income or education levels of participants; information
regarding the racial or ethnic distributions of the
participants was available for only eight of these studies.
- The reporting of the studies limited our ability to
accurately categorize age groups (e.g., adolescents, elderly),
socioeconomic status, or residence (urban versus rural).
Overall, the evidence indicated the need for greater
consistency in the reporting of target population characteristics,
so that key findings may be considered in relation to specific
populations. This would make it feasible, when the sample size
is adequate, to conduct subgroup analyses to assess whether
barriers to recruitment vary by sociodemographic and cultural
factors.
Key Question 2: Measures of Success
We sought to identify what measures of success (e.g.,
proportional representation relative to the U.S. population, or
proportional representation relative to incidence in a specified
population) have been used to evaluate the efficacy and/or
effectiveness of strategies for recruitment of underrepresented
populations into cancer prevention and treatment trials.
- All studies (n=23) were from the U.S. and 22 studies
targeted patients/participants for the recruitment
intervention; and over 50 percent of the studies were
based on multi-center cancer clinical trials conducted in
community settings (n=9) or hospital centers (n=7). 5-9,11,13,16,17,19-32
- Most of the reports were based on retrospective review of
enrollment to a single or multiple cancer trials.
- Only two articles reported having a recruitment goal for
the underrepresented group prior to enrollment in the
study. The majority of studies either defined recruitment
success as equaling the proportion of underrepresented
selected by the researcher (n=13) for various reasons or as
the disease-specific proportion of underrepresented (n =
9). The rest of the studies defined recruitment success as
equaling the geographic proportion of underrepresented
(n=2), or the local research institution's proportion of the
underrepresented (n=1).
- Very few studies evaluated recruitment success in
underrepresented groups especially those with low
socioeconomic status, Asian/Pacific Islanders, adolescents,
and rural populations (less than three studies in each
group). No study reported recruitment success measures
for American Indians/Alaska Natives.
The evidence reviewed indicated that success in recruitment
of underrepresented populations is defined primarily by the
goal of each study. When reporting on cancer trials,
investigators should give careful thought to success measures for
recruitment of underrepresented populations, avoid setting
such measures arbitrarily, and report recruitment results based
on the recruitment strategies for individual cancer clinical trials.
Key Questions 3 and 4: Methods to Study Recruitment
Strategies
We sought to identify recruitment strategies (e.g., media
appeals, incentives, etc.) that have been shown to be efficacious
and/or effective in increasing participation of underrepresented
populations in cancer treatment and prevention trials. We
found a total of five eligible articles. 6,7,9,11,17
The results of the interventions varied from no observed
improvement to an increase in recruitment into cancer clinical
trials. Two studies examined enrollment differences between
two different intervention methods. Two other studies
compared enrollment differences between interventions to a
control group. These control groups were either no
intervention (usual medical care from physicians) or a standard
recruitment "intervention" of mailed letters and telephone
contact. However, whether various interventions had a true
effect (null, positive, or negative) was somewhat unclear. Some
authors cautioned that their results could be due to factors such
as changes in recruitment strategy during the duration of the
intervention. To give a clearer picture, each of the five studies is
discussed in detail.
Linnan et al. investigated the differences between passive and
active recruitment into a home-based cancer prevention
randomized trial among employees.17 In the passive employee
contact arm, the research team contacted the employees from a
list of employee names and telephone numbers provided by the
company. In the active employee contact arm, employees
actively signed up to participate. While lower enrollment and
higher attrition were observed in the passive recruitment arm,
the passive method enrolled a more diverse group of
participants than did the active recruitment method.
Brewster, et al. examined differences in recruitment into
cancer prevention clinical trials between a clinic registry
method and a media campaign targeting Latina women.6 In the
media recruitment strategy, the study was advertised in flyers
placed in local community businesses, and advertised in
community and regional newspapers in English and Spanish.
The odds of presenting to the clinic and of recruitment were
nearly three times more successful via the media campaign than
via the clinic registry.
Paskett, et al. examined the effect of an intervention program
aimed at physicians and the community to increase the number
of rural patients with breast cancer or colorectal cancer in
clinical trials.7 The intervention program consisted of the
installation of a rapid tumor-reporting system to improve data
quality and to expedite the receipt of information on cancer
patients from physicians, a nurse facilitator who would notify
physicians of clinical trials, a quarterly newsletter mailed to
physicians about cancer treatment and clinical trials, and a
health educator who trained lay health educators and provided
community-based information about cancer screening,
treatment, and clinical trials. Five counties in North Carolina
received an intervention program while five counties in South
Carolina served as controls where usual medical care was
practiced. The rates of enrollment into clinical treatment trials
did not improve significantly in the intervention communities.
Moinpour, et al. reported the results of a randomized trial in
increasing participation of minorities.9 Minority recruitment
strategies were designed and implemented in five pilot sites:
African Americans in four sites and Hispanics in one site.
While each site had a minority recruiter who was given
requirements and a set of tasks, the specific details of the
minority recruitment interventions for each site were not given.
The overall impact was minimal, and it was unclear if, and at
which site the intervention was fully implemented.
Ford et al. examined recruitment differences among African
Americans randomized into either a control group or three
increasingly intensive intervention arms.7 The control group
used a standard method of recruitment such as a standard
recruitment letter, African-American or Caucasian interviewers
for eligibility screening, baseline information collection via
mailed packets, and reminder phone calls and mailings for
completion of the mailed packets (Arm D). The basic
intervention arm (Arm A) attempted to reduce potential
sociocultural and individual barriers through the use of an
enhanced recruitment letter and eligibility screening by African-
American interviewers. The second more intensive intervention
arm (Arm B) did not use mailed packets for baseline
information collection but telephone interviews to facilitate
ease of participation in addition to the enhanced recruitment
letter. The third, and most intensive, intervention arm (Arm C)
did not use a mailing packet or telephone interview but a
church-based project site to gather baseline information in
addition to the enhanced recruitment letter and eligibility
screening telephone calls by an African American. The authors
reported significantly higher enrollment yield (3.9 percent) in
the most intensive church-based, face-to-face recruitment
intervention arm (Arm C), compared to the other two
intervention arms (2.5 percent [Arm A] and 2.8 percent [Arm
B]) or the control group (2.9 percent [Arm D]) (p < 0.01).
There is only scant evidence in support of specific
interventions to improve recruitment to cancer clinical trials, as
indicated by the small number of studies comparing
interventions.
Key Question 5: Barriers and Promoters of Recruitment
We sought to identify the documented barriers and
promoters of participation for underrepresented populations in
cancer prevention and treatment trials. Our search yielded 45
eligible studies that were conducted in a variety of settings.3,5,8,13,22,23,25,26,29,33-63 Among the underrepresented populations, the
available studies targeted African Americans primarily (n=27),
as well as Latinos/Hispanics (n=7); American Indian/Alaska
Native (n=4 ); the elderly (n=14); adolescents (n=3);rural
populations (n=2); and Asian/Pacific Islanders (n=2). While
a large proportion of the available studies included populations
with low socioeconomic status, only one did so by design.9 The
search strategy yielded 40 U.S.-based studies, and we included
evidence from 5 non-U.S.-based studies that featured relevant
evidence.22
Barriers and promoters of participation in cancer
prevention and treatment trials
Types of barriers and promoters identified. Overall, the
eligible studies identified 118 distinct barriers to accrual to
cancer clinical trials, including 97 barriers to accrual to
therapeutic trials, 18 barriers to accrual to prevention trials, and
32 barriers to accrual to both therapeutic and prevention trials.
There were more reported barriers to opportunity (n=80) than
to awareness (n=7) or acceptance (n=40) of clinical trials. Of
the 59 distinct promoters of enrollment, most (n=29) were
promoters of the opportunity to participate in a cancer trial.
Barriers and promoters of accrual of African Americans to
cancer treatment trials. Overall, there were 19 studies of accrual
of African Americans to cancer therapeutic trials, which
reported 85 barriers to accrual to therapeutic trials, including
barriers to opportunity (n=56), barriers to acceptance (n =
28), and awareness (n=6). Of the 28 barriers to acceptance,
the most frequently reported were perceived harms of clinical
trial participation (n=8), mistrust of research, researchers, and
the medical system (n=10), and fear (n=5). Promoters were
predominantly of promoters of awareness (n=6). Of the
reported 14 promoters of opportunity, the most frequently
reported were culturally relevant education about trials (n=3),
and providing transportation (n=2). Of the 14 promoters of
acceptance, the most frequently reported were altruism (n=3),
perceived benefits of trial participation (n=5), and incentives
(n=5).
Barriers and promoters of accrual to therapeutic trials in
other underrepresented populations.
Latinos/Hispanics. Four
studies reported evidence on barriers to accrual of
Latinos/Hispanics to cancer therapeutic trials. The reported
eight barriers to opportunity were dominated by transportation
(n=2), age (n=1), toxicity of treatment (n=1), comorbid
conditions (n=1), and disease stage (n=1). Of the seven
barriers to acceptance, the most frequently reported was
mistrust of research and the medical system (n=2). Only two
of the eligible studies for this question reported evidence on
promoters of enrollment of Latinos/Hispanics. Brewster and
colleagues found that a media-based strategy was superior to a
clinic based strategy in recruiting Latino-Hispanic women.6
Others have reported the lack of adequate health insurance,
incentives, culturally relevant education about trials and the
perceived benefits of trial participation as additional promoters
of accrual for Latinos/Hispanics.5,55
American Indians/Alaska Natives. The amount of evidence
available for the American Indians/Alaska Natives population
with regard to accrual to clinical trials, in general, was very
limited. The aggregate number of American Indians/Alaska
Natives in all of the eligible studies for which data on
population subgroups was reported, was 19.35,41,43,55
Asian and Pacific Islanders.We did not find any evidence
regarding barriers or promoters of participation in cancer
prevention or treatment trial for the Asian and Pacific Islander
population.
The elderly. In the 11 available studies, barriers and
promoters of opportunity were predominant in this population.
Of the 22 barriers to opportunity, the most frequently reported
were age (n=2).
Adolescents. Only two of the available studies yielded
evidence, and reported the lack of available trials as a significant
barrier to enrollment of adolescents. Promoters of participation
for this population included the perceived benefits of trial
participation, including a chance for better treatment, and
altruistic motives.
Rural populations. Only two of the available studies focused
on recruitment of rural populations to cancer clinical trials,
including cross-sectional surveys of physicians,11 and focus
groups. The studies reported numerous barriers to awareness,
opportunity and acceptance of trial participation. They also
reported altruism and incentives (financial and otherwise) as
promoters.43
Barriers and promoters of accrual to prevention trials in
African-American populations. Overall, there were 13 studies
of barriers and promoters of accrual of African Americans to
cancer prevention trials. We did not include studies of accrual
to other types of primary prevention trials (e.g., diet and
exercise) in this systematic review. Among the 41 barriers to
accrual to prevention trials, barriers to opportunity (n=24)
were predominant, and of the 13 barriers to acceptance,
mistrust of research and the medical system (n=8), and the
perceived harms of clinical trial participation (n=4) were the
most frequently reported. Promoters included provision of
transportation (n=1) and incentives (n=2).
Chemoprevention trials.9,37,56 On average, each of the
chemoprevention trials reported two barriers (range: 1 to 2).
There were no barriers to awareness, two barriers to
opportunity, and three barriers to acceptance with mistrust of
research reported in two studies. In one study, promoters
included preference for the study's principal investigator to be
black, and the perception that it is better to be treated by
research doctors.
Smoking cessation trials.5,56,60 Out of the three smoking
cessation trials in African-American populations, only one trial
reported barriers to accrual, and not being ready to quit may
have been a confounding factor. The reported promoters were
incentives, support, encouragement, prayer, the certainty of
receiving actual medication, and the impact of diagnosis on risk
perception.
Screening trials.7 The results of this one study were discussed
in detail under key questions 3 and 4.
Barriers and promoters of accrual to prevention trials
among other underrepresented populations.
Latinos/Hispanics. Overall, there were four studies reporting
primarily barriers to opportunity (n=7), especially
transportation (n=2). Mistrust of research and the medical
system (n=2) and family considerations or issues (n=2) were
the most frequent barriers to acceptance.
American Indians/Alaska Natives and Asian and Pacific
Islanders. As discussed in the section on accrual to therapeutic
trials, very little information is available on these two
populations.
The elderly. Overall, there were three studies of barriers and
promoters of enrollment to cancer prevention trials in the
elderly. These studies reported three distinct barriers, age being
the most frequently cited (n=2). Among the three promoters
of accrual to prevention trials, there were no promoters of
awareness or acceptance. The three reported promoters of
accrual were the entry criteria, age and low-income status.
Rural populations. The available evidence on barriers and
promoters of accrual of rural populations to cancer prevention
and treatment trials is based on two studies that we discussed in
the section on barriers and promoters of accrual to therapeutic
trials.10,43
Key Question 5a: Effects of Demographic Factors
Overall, the available evidence for key question 5 suggested
that accrual to or intention to participate in a trial varied by the
following sociodemographic factors: age (n=16); gender
(n=3); socioeconomic status (n=4); and race/ethnicity
(n=4). These barriers and promoters related most frequently
to study design barriers, including exclusion by age (n=6),
study duration and visit structure (n=4), comorbid conditions
(n=7), and functional status (n=6). Few trials were available
for adolescents; and as expected, parental influence was
reported as a factor in decision-making only in this population.
However, the available evidence did not suggest age as a factor
that reduced awareness or acceptance of participation.
Key Question 5b: Effects of Cultural Factors
Three of the studies reported that barriers or promoters of
enrollment varied by cultural factors;39,55,60 however, it is not
entirely clear whether such "cultural factors" refer to cultural
norms, values or beliefs. For the elderly population, enrollment
barriers and promoters did not vary by culturally relevant
factors other than race or ethnicity. The heterogeneity of the
available evidence and the definitional overlap among several of
the underrepresented populations limited our ability to
synthesize the evidence regarding whether some barriers or
promoters vary by cultural factors.
Key Question 6: Role of Provider Attitudes and
Perceptions
Nine studies presented data on how provider
attitudes/perceptions were attitudes to and promoters of accrual
to cancer clinical trials. Four studies found provider attitudes
as a barrier to enrollment11,23,44,64 while one study found provider
attitudes to be a promoter of patient accrual.23 The studies also
reported that patient age,23,59,65 comorbidity,23,59 disease stage,23
mistrust of researchers,23,31 and lack of physician awareness
about trials44,52 were factors that prevented providers from
enrolling their patients into clinical trials. Two studies64,66 found
that provider communication or method of presentation were
barriers to patient enrollment, whereas one study found it to be
a promoter of trial enrollment.41
For studies that targeted minority populations,29,44,52 mistrust
of researchers and lack of provider awareness about trials were
leading provider barriers44,52 that decreased patient enrollment
in clinical trials. Additionally, concerns about patient noncompliance
and a lack of available protocols were reasons cited
for not talking to patients about clinical trials.29 For studies that
targeted the elderly, provider attitudes regarding clinical trials
prevented them from sharing information about trials with
their patients in one study,23 and increased their willingness to
enroll patients in clinical trials in another study.41
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