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Ford JG, Howerton MW, Bolen S, et al. Knowledge and Access to Information on Recruitment of Underrepresented Populations to Cancer Clinical Trials. Rockville (MD): Agency for Healthcare Research and Quality (US); 2005 Jun. (Evidence Reports/Technology Assessments, No. 122.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Knowledge and Access to Information on Recruitment of Underrepresented Populations to Cancer Clinical Trials

Knowledge and Access to Information on Recruitment of Underrepresented Populations to Cancer Clinical Trials.

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2Methods

The NCI requested an evidence report to synthesize the available evidence on the effect of interventions to increase participation by underrepresented populations in clinical trials, with an overall goal of improving the opportunities for underrepresented populations to participate in cancer-related clinical trials. The EPC was awarded this contract in December 2003. We established a team and work plan to develop the evidence report. The project consisted of recruiting technical experts, formulating and refining the specific questions, performing a comprehensive literature search, summarizing the state of the literature, constructing evidence tables, and submitting the report for peer review.

Recruitment of Technical Experts and Peer Reviewers

At the beginning of the project, we recruited a panel of internal and external technical experts to give us input on key steps including the selection and refinement of the questions to be examined. The panel included seven internal technical experts from the Johns Hopkins University who had expertise in various aspects of recruitment strategies for controlled clinical trials and 15 external experts who had special interests in underrepresented populations (see Appendix A). Many of our external experts also were a part of the NCI Special Populations Network (SPN).37 In addition to this panel of technical experts, we recruited a group of peer reviewers to examine a draft of the evidence report, as described further in the section on Peer Review. This group included representatives of organizations or agencies having different perspectives on the topic (See Appendix A). We also sought input throughout the project from representatives of the NCI.

Key Questions

We refined the original questions provided by AHRQ after obtaining input from the technical experts and NCI representatives. Listed below are the Key Questions addressed in this report.

  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. We included the elderly as underrepresented because of concerns that they are not recruited into trials as aggressively as younger patients when diagnosed as having cancer. We included adolescents as underrepresented because of concerns that they may be more resistant to participating in cancer-related trials than adults.
  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?
  3. 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 trials?
  4. Which recruitment strategies have been shown to be efficacious and/or effective in increasing participation of underrepresented populations in cancer prevention trials?
  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 exclusion by design. Examples of potential promoters include attitudes, altruism, advanced disease, financial incentive, and no-cost treatment.
    1. How do these barriers and promoters differ by age, gender, socioeconomic status, or race/ethnicity?
    2. How are these barriers and promoters modified by cultural factors?
  6. What effects do the attitudes and perceptions of healthcare providers have on the efficacy/effectiveness of strategies for recruitment of underrepresented populations into cancer prevention and treatment trials? Healthcare providers are defined as including any health professional or healthcare organization that provides health services to patients.

Conceptual Framework

We constructed a conceptual framework for our questions based on the relationships among the factors leading to a patient's decision to enroll in a cancer-related clinical trial (see Figure 1). This framework was derived from a conceptual model developed by two members of the EPC team.39

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 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 recruitment into a trial, including: 1) patients/clients receiving information about clinical trials in general through healthcare providers or their own social ties, and subsequently accepting a specific opportunity to participate in the 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 to and promoters of awareness, opportunity, and acceptance/refusal.

In the hypothesized conceptual framework, there are several factors that are promoters of or barriers to clinical trial awareness. First, a person must know about and believe in the value of participating in the clinical trial before one can agree to participate. Knowledge about a clinical trial involves knowing what the anticipated outcomes may be, the costs of participation in terms of money, time, and effort, as well as information about the disease. Second, a person's attitudes and beliefs regarding cancer, the medical profession, and medical research may influence their willingness to receive and attend to information about clinical trials. Third, a person's belief in his/her ability to participate in a clinical trial, or self-efficacy, may influence awareness of the clinical trial. If individuals do not believe that they can participate in the trial, then they may not be open to hearing information about the trial. Fourth, the organizational environment, which involves the physical and psychosocial environment in which the information is being disseminated as well as the trial is being conducted, may influence a person's willingness to receive information about clinical trials. If the organizational environment makes patients/clients uncomfortable or defensive, then they will be less open to recruitment efforts. The final hypothesized barrier to or promoter of clinical trial awareness is health literacy. A lack of understanding of the medical system, cancer, and health information in general lead to poor health literacy, making patients less inherently aware about clinical trials as well as more difficult to educate them about trials.

As denoted in the conceptual framework, individuals must have an opportunity to participate in a clinical trial before they can accept or refuse participation. Some barriers and promoters of opportunity are access to the hospital or clinical trial site, trial eligibility, advanced disease, comorbidities, and medical insurance status. Additionally, providers can play a vital role in the successful recruitment of patients to clinical trials in that they are often the gatekeepers of information about clinical trials. They can decide which patients to refer for trial participation. Therefore, provider knowledge, attitudes, and beliefs about clinical trials and their patients' abilities to enroll in the trials may influence their disseminating information about the trials (key question 6).

The third main component of the conceptual framework involves acceptance/refusal of trial participation. The decision to accept or refuse enrollment in a clinical trial is based on many factors, which often involves a decisional balance. For example, do the perceived benefits outweigh the perceived harms? If so, then people are more likely to agree to enroll in a trial. Also, trust in the sponsor, physician, or investigator may play a large role in whether people are willing to participate in a clinical trial. Other factors that are important to acceptance/refusal are self-efficacy, quality of life, advanced disease, no cost treatment, financial incentives, as well as personal experience with cancer, the medical system, and clinical trials. The timing of the trial may also influence the decision to participate. For an example, a person who has just been diagnosed with cancer may be more or less willing to participate than someone who is at the end-stage of cancer. Finally, religious beliefs and altruism may play a role in the decision regarding participation.

Encompassing clinical trial awareness, opportunity, and acceptance/refusal are sociodemographic factors that serve as moderators/covariates of participation. These sociodemographic factors include race/ethnicity, age, gender, geography, language, income, social ties, education, and culture. In the hypothesized conceptual framework, each of these factors influences individual barriers to and promoters of awareness, opportunity, and willingness to participate in cancer clinical trials among underrepresented populations.

As part of this report, we evaluated interventions to increase accrual to cancer clinical trials (Key Questions 3 and 4). The types of interventions targeted were directed at individuals, physicians/providers, the medical system, and the community; and intervention strategies varied, including incentives, as well as media-based campaigns. Based on our conceptual framework, interventions are directed at decreasing barriers to and/or promoters of clinical trial awareness as well as opportunities for participation and willingness to participate or actual enrollment. In addition, we looked at the types of studies used to address the recruitment of underrepresented populations to clinical trials (Key Question 1). These were expected to be primarily surveys, focus groups, and concurrent controlled trials (CCT) (both randomized and non-randomized). Finally, as denoted in the bottom right of the conceptual framework, we attempted to assess whether investigators reported on measures of success (Key Question 2). For example, if a recruitment goal was stated a priori, was that goal achieved? We attempted to identify the different ways recruitment success was measured. Some examples of potential success measures are proportional representation relative to the U.S. population and proportional representation relative to cancer incidence.

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). This electronic search strategy was not limited by year of publication, and the MEDLINE database goes back to 1966

Hand searching for possibly relevant citations took several forms. Our experts identified 34 journals that were thought to be most likely to contain relevant studies (see Appendix B). 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® (ISI ResearchSoft, Berkeley, CA), a reference management software package, 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 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 articles for consideration. We also used MEDLINE to search for articles published by selected experts known to have interests related to our Key Questions.

Finally, we examined the reference lists of eligible articles to identify any potentially relevant ones. This task was completed by the second reviewer as part of the article review process (see description of article review process below).

Search Terms and Strategies

Search strategies, specific to each database, were designed to maximize sensitivity. Initially, we developed a core strategy for MEDLINE, accessed via PubMed, based on an analysis of the Medical Subject Headings (MeSH) and text words of key articles identified a priori. The PubMed strategy formed the basis for the strategies developed for the other electronic databases (see Appendix C).

General search terms

MEDLINE general search terms: (neoplasm [mh] OR cancer [tw] OR carcino*[tiab] OR tumor [tiab] OR oncolog*[tiab]) AND (patient selection [mh] OR recruit*[ti] OR participat*[ti] OR enrol*[ti] OR enlist*[ti]) AND eng [la] NOT (animal [mh] NOT human [mh]).

PsychINFO general search terms: (neoplasm or cancer or carcinogen or tumor or oncolog*) and (patient selection or TI recruit* or TI participat* or TI enrol* or TI enlist* or TI refer*) and (trial* or stud*) And LA english and human.

CINAHL general search terms: (neoplasm or cancer or carcino* or tumor or oncolog*) and (MW patient selection or MW research subject recruitment or TI recruit* or TI participat* or TI enrol* or TI enlist* or TI refer*) and (trial* or stud*) and LA English and human.

Cochrane Database (CENTRAL and Methodology Review) general search terms: (neoplasm* or cancer or carcino* or tumor* or oncolog*) and (patient selection or recruit*:ti or particip*:ti or enrol*:ti or enlist*:ti or refer*:ti) and (trial* OR stud*) NOT (animal NOT human).

C2-SPECTR: {neoplasm} or {cancer} or {carcino} or {tumor} or {oncolog}

OR All Non-Indexed Fields: {neoplasm} or {cancer} or {carcino} or {tumor} or {oncolog} AND All Non-Indexed Fields {patient selection} or {recruit} or {participat} or {enrol} or {enlist} or {refer} AND All Non-Indexed Fields {trial} or {stud} NOT All Non-Indexed Fields {animal} NOT {human}.

Organization and Tracking of Literature Search

Whenever possible, the results of the searches were downloaded and imported into ProCite. We used the duplication check in the bibliographic software ProCite to include in the Recruitment Citations Database only articles that were not previously retrieved. This database was used to store citations and to track the search results and sources. We also used this database to track the results of the title and abstract review processes and the retrieval of the full text copies of articles (see Figure 2).

Figure 2. Summary of literature search and review process (number of articles).

Figure

Figure 2. Summary of literature search and review process (number of articles).

Title Review

After the electronic databases were searched and citations downloaded into ProCite, the study team scanned all of the titles. During the scan, team members deleted any titles that did not apply to the study topics. Title scans were conducted in a parallel fashion by two independent reviewers. If a title was selected as irrelevant by both reviewers, it was tagged in the ProCite database and deleted from further study.

Abstract Review

Specific inclusion and exclusion criteria were applied at each of the levels of review, with criteria becoming more stringent as the process moved from searching, to the review of titles, to the review of abstracts, and to the review of articles. After identifying a title as potentially relevant, two team members independently reviewed the abstract of the citation, and articles were included or excluded from the article review on this basis. Disagreements between reviewers were adjudicated by consensus.

Inclusion and Exclusion Criteria

During the abstract review process, emphasis was placed on identifying all articles that could have original data pertinent to the questions about recruitment of underrepresented populations into cancer prevention and treatment trials. As previously described, representatives from NCI were consulted during the development of inclusion and exclusion criteria.

In evaluating titles and abstracts, the following criteria were used to exclude articles from further consideration:

  • Not written in English.
  • Did not include human data.
  • No original data.
  • Meeting abstract only (no full article for review).
  • Did not address cancer treatment or prevention.
  • Did not report a controlled trial or discuss recruitment to a controlled trial.
  • Article did not apply to any of the study questions.

For citations relevant to Key Questions 3 and 4, we limited eligibility further to studies that compared at least two groups. This comparison group could include groups from randomized and non-randomized designs with concurrent or historical controls. Non-controlled designs (e.g., case series with no comparison groups) were excluded for Key Questions 3 and 4, but remained potentially eligible for Key Questions 1 and 2.

When the initial exclusion criteria were developed, “not a U.S.-based study” was an exclusion criterion. As the review process progressed, however, the EPC team determined that this exclusion criterion might delete some articles from the review that could provide important information. Abstract reviews were then conducted on articles initially excluded because they were not U.S.-based studies. A number of articles were then eligible for article review that would not have been eligible otherwise. We included studies that addressed underrepresented minority populations using whatever definitions of race/ethnicity were provided by the study authors.

Abstract Review Process

We reviewed abstracts by printing titles and abstracts of all articles retrieved by the literature search on a standardized form and distributing them to two reviewers (see Appendix D *). The reviewers independently screened the abstracts for eligibility and classified them by research question addressed. When reviewers agreed that a decision regarding eligibility could not be made because of insufficient information, the full article was retrieved for review.

The results of the abstract review process were entered into the Recruitment Citations Database. Deleted citations were tagged with the reason for exclusion. Citations were returned to the reviewers for adjudication if there was disagreement on eligibility.

Article Review

The purpose of the article review was to confirm the relevance of each article to the research questions, to determine methodological characteristics pertaining to study quality, and to collect evidence that addressed the research questions. Articles eligible for full review could address more than one of the Key Questions. If reviewers felt this was the case multiple forms were used.

Quality Assessment and Data Abstraction

Forms were developed to confirm eligibility for a full article review, to assess study characteristics, and to extract the relevant data to address the study questions (see Appendix E). The forms were developed through an iterative process that included the review of forms used for previous EPC projects, discussions among team members, and pilot testing. This process was complex because of the heterogeneity of the literature. We developed a general form and question-specific content review forms for the abstraction of data to address Key Questions 1 and 2, 3 and 4, and 5 and 6. We used one form to assess the quality of articles eligible for Key Questions 3 and 4, and a separate form to assess the quality of articles eligible for Key Questions 5 and 6. A quality assessment form was not used for articles eligible for Key Questions 1 and 2 because the questions called for only a listing of methods that have been used. The forms were color coded to aid reviewers.

Assessment of the quality of individual studies

  • The study quality assessment form Key Questions 3 and 4 had six sections and was completed only for studies that met the criteria for these Key Questions.
    • The first section addressed the representativeness of the study populations, thus allowing the reviewers to assess each study's descriptions of setting and population as well as the inclusion/exclusion criteria and the characteristics of participants/non-participants.
    • The second section was used to evaluate potential bias and confounding factors.
    • The third section assessed the description of the recruitment strategy by evaluation of the details of the flow of participants through the clinical trial and the details of the recruitment strategy.
    • The fourth section assessed the reporting of recruitment outcomes and follow-up. It included the description of the measures used to define barriers and promoters to recruitment and each study's reporting of the reasons for withdrawal from the study.
    • The fifth section assessed the statistical quality and interpretation, and the sixth covered conflict of interest. The last item called for an overall rating of the quality of the study.
  • The study quality assessment form for Key Questions 5 and 6 had three sections.
    • The first section covered the representativeness of the study population in much the same manner as the quality assessment form for Key Questions 3 and 4.
    • The second section was designed to assess the quality of survey studies.
    • The third section was designed to assess the quality of qualitative studies.

Data abstraction

A separate general abstraction form was used for each question to abstract information such as study design, intervention, study location, objectives, target population characteristics, and timeline. Additional question-specific forms were used for Key Questions 1 and 2, Key Questions 3 and 4, and Key Questions 5 and 6. Each of these three forms addressed questions dealing specifically with the respective Key Questions.

Article Review Process

We used a serial article review process. In this process, the quality assessment and data abstraction forms were completed by the primary reviewer. The second reviewer, after reading the article, performed an independent assessment of the study's quality using a separate quality assessment form and then checked each item on the data abstraction form for completeness and accuracy. The reviewer pairs were formed to include personnel with both clinical and methodological expertise. A third reviewer re-reviewed all articles that were marked as “ineligible” by the first two reviewers to ensure consistency in the classification of the articles. Reviewers were not masked to the articles' authors, institution, or journal. In most instances, data were directly abstracted from the article. If possible, relevant data were also abstracted from figures.

All information from the article review process was entered in a relational database (Recruitment Evidence Database). The database was used to maintain and clean the data, as well as to create detailed evidence tables (see Appendix F ) and summary tables (see Tables 1 to 7).

Table 1. Summary of the Characteristics of Studies about Strategies to Recruit Underrepresented Populations to Cancer Prevention and Treatment Trials (Key Question 1).

Table 1

Summary of the Characteristics of Studies about Strategies to Recruit Underrepresented Populations to Cancer Prevention and Treatment Trials (Key Question 1).

Table 7. Summary of Studies on the Effects of Attitudes and Perceptions of Healthcare Providers on the Effectiveness of Strategies for Recruitment of Underrepresented Populations into Cancer Prevention and Treatment Trials (Key Question 6).

Table 7

Summary of Studies on the Effects of Attitudes and Perceptions of Healthcare Providers on the Effectiveness of Strategies for Recruitment of Underrepresented Populations into Cancer Prevention and Treatment Trials (Key Question (more...)

Grading of the Total Body of Evidence

After all articles were reviewed, we graded the total body of evidence supporting each question on the basis of its quantity, quality, and consistency. Our evidence-grading scheme followed the approach recommended by the International GRADE Working Group.40 In terms of quantity of evidence for each question, we determined the number of studies and the total number of patients studied. We assessed the quality and consistency of evidence on each key question based on the criteria recommended by the Grade Working Group that applied to the questions (see Tables 8 to10). Although the GRADE criterion were developed primarily for treatment effectiveness questions, they are based on fundamental principles that apply to a variety of study questions. As shown in Tables 8 to 10, we downgraded our grading of the evidence if any of the following criteria were met: 1) if the studies had serious limitations in quality; 2) if the studies had important inconsistency; 3) if there was uncertainty about the directness or extent to which the people, measures and/or outcomes are similar to those of interest; 4) if data were imprecise or sparse; and 5) if the studies had high probability of reporting bias.

Table 8. Grading of the Quality of Evidence on the Efficacy or Effectiveness of Strategies for Recruiting Underserved Populations Into Cancer Prevention and Treatment Trials (Key Questions 3 and 4).

Table 8

Grading of the Quality of Evidence on the Efficacy or Effectiveness of Strategies for Recruiting Underserved Populations Into Cancer Prevention and Treatment Trials (Key Questions 3 and 4).

Table 10. Grading of the Quality of Evidence on the Effects of Attitudes and Perceptions of HealthCare Providers on Recruitment of Underserved Populations Into Cancer Prevention and Treatment Trials (Key Question 6).

Table 10

Grading of the Quality of Evidence on the Effects of Attitudes and Perceptions of HealthCare Providers on Recruitment of Underserved Populations Into Cancer Prevention and Treatment Trials (Key Question 6).

Peer Review

Throughout the project, feedback was sought from the technical experts through ad hoc and formal requests for guidance. A draft of the completed report was sent to the technical experts and peer reviewers, as well as to the representatives of the NCI and AHRQ. Substantive comments were entered into a database. Revisions were made to the evidence report as warranted, and a summary of the comments and their disposition was submitted to AHRQ with the final report.

Footnotes

Note: Appendixes cited in this report are provided electronically at: http://www​.ahrq.gov/clinic/tp/recruittp​.htm

Note: Appendixes cited in the report are provided electronically at: http://www​.ahrq.gov/clinic/tp/recruittp​.htm

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