- Email: [email protected]
Mistrust of Pediatric Sickle Cell Disease Clinical Trials Research
Mistrust of Pediatric Sickle Cell Disease Clinical Trials Research Evelyn M. Stevens, MPH,1 Chavis A. Patterson, PhD,1,2 Yimei B. Li, PhD,1,2 Kim Smith-Whitley, MD,1,2 Lamia P. Barakat, PhD1,2 Introduction: Sickle cell disease (SCD) research is hampered by disparities in participation due in part to mistrust of research among racial/ethnic minorities. Beyond the historic context of research misconduct, little is known about the associations of social ecologic factors with mistrust and of mistrust with SCD clinical trials enrollment. This study evaluated proximal (age, gender, disease severity, perceived stress, SES) and distal (religious beliefs, social support, instrumental support) factors related to mistrust of research among caregivers of children with SCD and adolescents and young adults (AYAs) with SCD.
Methods: Over an 18-month period (2009–2010), participants completed questionnaires of perceived barriers and benefits to clinical trials enrollment, perceived stress, and self-reported demographic and disease-related information. Analyses (January–June 2015) used multivariable linear regressions to evaluate predictors of mistrust. Results: Data were analyzed for 154 caregivers (mean age, 38.75 years; SD¼9.56 years; 90.30% female) and 88 AYAs (mean age, 24.76 years; SD¼7.25 years; 46.40% female). Among caregivers (full model, R2¼0.14, pr0.001), greater mistrust was explained by higher perceived stress (β¼0.04, p¼0.052); religious beliefs (β¼0.61, pr0.001); and greater instrumental support (β¼0.07, p¼0.044). Among AYAs (full model, R2¼0.18, pr0.001), higher mistrust was explained by being male (β¼–0.56, pr0.001) and lower instrumental support (β¼–0.11, p¼0.016). Mistrust was significantly greater among caregivers that reported no prior involvement in medical research (p¼0.003). Conclusions: By understanding the complexity through which social ecologic factors contribute to mistrust, researchers may create targeted strategies to address mistrust and increase engagement in SCD research for caregivers and AYAs. (Am J Prev Med 2016;51(1S1):S78–S86) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
S
ickle cell disease (SCD) affects approximately 70,000–100,000 Americans and is one of the most common chronic conditions affecting primarily racial and ethnic minorities (e.g., African ancestry, Hispanic, Mediterranean, and Asian descent).1–3 Relatedly, many factors contribute to health disparities seen in SCD, From the 1The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and 2Perelman School of Medicine of The University of Pennsylvania, Philadelphia, Pennsylvania Address correspondence to: Evelyn M. Stevens, MPH, The Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard, Colket Translational Research Building 10300-06, Philadelphia PA 19104. E-mail: [email protected]. This article is part of the supplement issue titled Developing a Unified Approach for Sickle Cell Disease. 0749-3797/$36.00 http://dx.doi.org/10.1016/j.amepre.2016.01.024
including disproportionate percentages of these populations living in poverty and having limited access to specialized care.2–7 The conduct of therapeutic clinical trials to evaluate the feasibility, acceptability, and efficacy of new treatments and technologies among diverse samples is critical to decreasing health disparities and improving long-term health outcomes.8 A recent review revealed that 25 (14%) of the 174 SCD clinical investigations registered with ClinicalTrials.gov were terminated or withdrawn owing to low enrollment, suggesting a need for researchers to continue evaluation of racial/ethnic minorities’ attitudinal beliefs about SCD clinical trials research.9 Mistrust of research, defined through two concepts, cultural mistrust (suspicion of European Americans based on history of racism and unfair treatment) and medical mistrust (overall distrust of the healthcare system), is a frequently cited barrier accounting for
S78 Am J Prev Med 2016;51(1S1):S78–S86 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
overall satisfaction with care and inadequate enrollment of minorities in clinical trials.10–14 Mistrust is often linked to historic misconduct with minorities in research, particularly exploitation of African Americans in medical research (i.e., Tuskegee Syphilis Study).12,15 Although federal guidelines were developed over the past two decades to improve representation of disenfranchised populations in research,16 mistrust is still prevalent and minorities remain under-represented in clinical trials research.8,17,18 Studies among pediatric patients with SCD and their caregivers have focused on barriers to clinical trials enrollment, including study design and practical considerations (i.e., time and demands).19,20 Limited literature highlights mistrust of research as a significant barrier to clinical trials enrollment among the SCD community.21– 24 Most of these studies used qualitative data gathered through focus groups of pediatric patients and their caregivers and were limited by small sample sizes, evaluated attitudes toward enrollment in a specific clinical trial, or evaluated attitudes toward the amount of SCD research conducted as opposed to perceived benefits and barriers toward research.22–24 Additionally, none evaluated factors related to mistrust of research. More effective redress of the barrier of mistrust requires increased understanding of disease-related and psychosocial contributors, which will allow researchers to frame SCD research in a manner that gains community acceptance and increases informed consent. Relevant to this effort, prior work systematically evaluated perceived benefits and barriers of pediatric clinical trials enrollment for SCD and asthma patients and their caregivers based on The Social Ecologic Model.25,26 The social ecology of children with chronic health conditions describes multiple, bidirectional influences on a child and family’s adaptation to the chronic condition. These influences, from proximal to distal variables and organized at each level of a child’s social ecology, are patient, caregiver and family, community, and society/culture.27 Factors affecting research participation may connect to factors influencing mistrust. For example, perceived severity of a child’s illness (a patientlevel variable) has been noted as a factor affecting parents’ willingness to allow their child to participate in research.19 Disease severity can increase stress and anxiety among caregivers and patients, particularly in families that are challenged with management of SCDrelated complications,28,29 and an association between perceived stress and greater mistrust among caregivers of children with SCD and asthma has been established.25 Additionally, minorities may experience stress related to economic difficulties (a family-level variable). Researchers have made attempts to reduce SES-related July 2016
S79
barriers to research participation by offering instrumental support, or tangible and physical support provided to assist people with participating in a clinical trial (e.g., compensation, transportation, child care, access to care).30 Successful use of these supports to encourage participation in clinical trials has been mixed, with some suggesting incentives are an effective recruitment strategy and others noting that incentives have no impact on parents’ decisions to enroll their child in research.31–33 Other factors that influence minority research participation, potentially contributing to mistrust of research, include religious beliefs countering medical science14,34,35 and social supports (e.g., family and friends support research participation).25 Minority families have strong religious beliefs and supportive social networks that are often extremely important within their community. Although medical decision making and healthcare utilization are often influenced by religion and social networks (a society/culture variable),36,37 it is unclear how and to what extent religion and social support influence mistrust. The purpose of this study was to evaluate proximal (age, gender, disease severity, perceived stress, and SES) and distal (religious beliefs, social support, and instrumental support) social ecologic factors as contributors to mistrust among caregivers of children with SCD and adolescents and young adults (AYAs) with SCD. It was hypothesized that greater disease severity, greater perceived stress, religious beliefs countering medical science, and lower social and instrumental support would be associated with greater mistrust of research and having an older child or being an older AYA, being male, and having lower SES would be associated with greater mistrust. Furthermore, greater mistrust was expected to be associated with no prior involvement in research.
Methods This study was performed using data from a multisite study, which evaluated perceived benefits and barriers to pediatric clinical trials participation through development and initial validation of the Pediatric Research Participation Questionnaire (PRPQ).25,26 The PRPQ was developed in four phases that included item generation from the project team, community partners, and SCD medical experts; tailoring of the items for caregivers and for AYAs and children with SCD or asthma; review of the measure by stakeholders; and pilot testing to ensure clarity and ease of administration. The study protocol was approved by the appropriate IRBs. Data were collected over an 18-month period in 2009–2010. An exploratory factor analysis was conducted to identify latent structures of the questionnaire of which mistrust of research/ researchers was identified as a primary consideration affecting decisions to participate in clinical trials.25
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
S80
Study Sample
Measures
In the parent study, 296 of 385 (77.1%) consented to participate; 20.1% (n¼78) refused participation; and 2.8% (n¼11) did not meet inclusion criteria. Reasons for refusal are described elsewhere.25 For this secondary analysis, only caregivers of children with SCD (n¼154) and AYAs (aged Z16 years) with SCD (n¼88) were included. Participants were recruited from East Coast pediatric SCD centers and an adult outpatient clinic associated with the medical universities that provided care for many AYA patients that transitioned out of pediatric care. All participants completed the PRPQ on paper and in private during clinic appointments. A research assistant was available to address health literacy issues. The PRPQ assessed attitudes (with a binary response category of agree or disagree) toward medical and psychosocial research studies to aid in understanding decision making about clinical trials enrollment.
Mistrust of research/researchers, social support, and instrumental support (tangible or physical support offered to encourage trial participation) were factors identified in the exploratory factor analysis of the PRPQ as contributors to clinical trials enrollment decisions. The items that loaded on these factors were used to compute a total score, with higher scores indicating greater levels of mistrust, social support, and instrumental support (Table 1). Reliability was adequate for each of these variables among caregivers and AYAs (mistrust, α¼0.70 and α¼0.66; social support, α¼0.76 and α¼0.80; instrumental support, α¼0.70 and α¼0.68; respectively). Religious beliefs were assessed through one item of the PRPQ that reads: Researchers sometimes undermine the power of God and God’s will. In addition, one item of the social support scale asked participants if their religious leader would want me/my child to be in research (Table 1).
Table 1. Study Measures Mistrust of research/researchers Total score of the following items: 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11)
We participate in research because the healthcare team takes good care of my childa The government sometimes exposes research participants to medicine and procedures known to be harmful to one’s healtha Research is a part of a conspiracy to harm minority groups We are willing to participate in research when we know exactly what we will be asked to doa The healthcare team will view me/my child only as a research participant if I enroll The healthcare team will treat me/my child differently if I enroll When the researcher is of the same race I am more likely to participate Researchers sometimes hide information from participants prior to research Researchers ask for financial information that may get back to the government and cause me to lose my check/benefits Personal information given in research does not stay private and might hurt me/people I care about Researchers are motivated by their own career goals and not the welfare of their participants
Social support of research participation Total score of the following items: 1) 2) 3) 4)
My family would want me/my child to be in research My friends would want me/my child to be in research My religious leader would want me/my child to be in research My community agency would want me/my child to be in research
Instrumental support for research Total score of the following items: 1) 2) 3) 4) 5) 6) 7)
I/We would participate in research if we could learn more about my/my child’s illness I/We would participate in research if we could get tests/medicine my insurance won’t cover I/We would participate in research if we could get tests or medicine not available to the public More people would participate in research if researchers provide childcare More people would participate in research if researchers provide money or gifts More people would participate in research if researchers cover transportation costs More people would participate in research if researchers provide telephone/internet participation
Religious beliefs Endorsement of the following item: 1) Researchers sometimes undermine the power of God and God’s will. 2) My religious leader would want me/my child to be in research. Note: All items were derived from the Pediatric Research Participation Questionnaire (PRPQ) and loaded on one of the four-factor structures that were identified during an exploratory factor analysis of the PRPQ (Barakat et al., 2013).25 a Items did not load on the mistrust factor of the PRPQ but were added to mistrust measure because they were identified as barriers to research participation related to mistrust. The addition of these items resulted in greater reliability.
www.ajpmonline.org
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
S81
The Perceived Stress Scale four-item short form of the 14-item measure evaluated the degree to which participants perceived their lives as stressful. The Perceived Stress Scale showed acceptable reliability in prior validation studies.38 Reliability was adequate for caregivers (α¼0.66) and marginal for AYAs (α¼0.53).25 Participants completed a General Information Form to collect demographic and disease-related information and prior involvement in medical research (coded as yes/no). Disease severity was assessed by SCD genotype; healthcare utilization (total number of daily medications, treatments, and hospitalizations in the past year); and SCD complications (total number of medical and psychosocial diagnoses). Demographics included age of child/ AYA with SCD, gender of caregiver or AYA completing the questionnaire, education level of caregiver or AYA, and monthly household income.
Statistical Analysis Analyses were conducted separately for caregivers and AYAs during January–July 2015. Descriptive statistics were computed for all study variables checking for outliers and distribution. Fisher exact tests, t-tests, Spearman correlations, and linear regressions were used for hypothesis testing. All variables correlated with mistrust (pr0.10) were included in the linear regression models. Hierarchical linear regression models were computed based on the Social Ecologic Model from proximal to more distal—patientand family-level variables on the first step (demographics, disease severity, perceived stress, and SES) and community-level variables on the second step (instrumental support, beliefs about religion, and social support) (Figure 1). A two-sided p-value o0.05 was considered statistically significant for hypothesis testing. Power was 40.80 for detecting medium effects with 0.05 Type I error. All of the analyses were performed in SPSS, version 22.
Results
Figure 1. Factors related to mistrust of clinical trials research: social ecologic framework.
Participants included 154 caregivers (mean age, 38.75 years; SD¼9.56 years) and 88 AYAs (mean age, 24.76 years; SD¼7.25 years) (Table 2). Majority of caregivers and AYAs self-identified as Black or African American (caregivers, 92.20%; AYAs, 96.60%) and all participants self-identified as Non-Hispanic/Latino. SCD genotype SS was most common among AYAs (73.90%) and the children of the caregivers (59.70%). Mistrust, instrumental support, and social support scores did not differ significantly between caregivers and AYAs. Among caregivers, greater instrumental support (r ¼0.18, p¼0.02) and religious beliefs countering medical science (r¼0.28, pr0.000) were significantly correlated with greater mistrust of research (Table 3). There was a trend toward significance for higher perceived stress with greater mistrust among caregivers (r¼0.15, p¼0.069). Among AYAs, lower instrumental support was significantly correlated with lower mistrust (r¼–0.25, p¼0.19). Mistrust differed significantly between female AYAs (mean¼1.03, SD¼0.79) and male AYAs (mean¼1.58, SD¼0.69, pr0.001). Variables found to be associated with mistrust (po0.10) for
caregivers (perceived stress, religious beliefs, and instrumental support) and AYAs (gender and instrumental support) were further evaluated as predictors of mistrust in regression analyses. For caregivers, higher perceived stress contributed significantly to greater mistrust (β¼0.05, p¼0.028) (Table 4). Religious beliefs and instrumental support were added to the model and were also identified as significant predictors of mistrust (β¼0.61, p¼0.000 and β¼0.07, p¼0.044, respectively), such that religious beliefs countering medical science and greater instrumental support predicted greater mistrust among caregivers. Collectively, perceived stress, religious beliefs, and instrumental support explained 14% of the variation in mistrust (full model, F[3,148]¼8.24, R2¼0.14, p¼0.000). Among AYAs, patient gender contributed significantly to mistrust, with male AYAs having greater mistrust as compared with female AYAs (β¼–0.55, p¼0.000). Instrumental support was also a significant independent predictor of greater mistrust (β¼–0.11, p¼0.016). Both
July 2016
S82
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
Table 2. Participant Demographic, Medical, and Summary Score Characteristics
Demographics
Caregiver, n (%) (n¼154)
Adolescent and young adult, n (%) (n¼88)
139 (90.30%)
41 (46.60%)
15 (9.70%)
47 (53.40%)
38.75 (9.56)
24.76 (7.25)
154 (100.00%)
88 (100.00%)
142 (92.20%)
85 (96.60%)
3 (1.90%)
2 (2.30%)
Gender Female Male Age (years), M (SD) Ethnicity Non-Hispanic/Latino
Mistrust was significantly greater in caregivers that reported no prior involvement in medical research (mean¼1.33, SD¼0.77) compared with caregivers that reported prior involvement (mean¼0.94, SD¼0.79, t[152]¼3.02, p¼0.003, d¼0.51). There was no significant difference in mistrust based on prior involvement in medical research for AYAs.
Race Black or African American White
Discussion
Mistrust has been cited as a barrier to clinical trials enrollEducation ment among the SCD communSome high school 11 (7.10%) 27 (30.70%) ity.21–24 This study is among the High school graduate 48 (31.20%) 23 (26.10%) first to evaluate factors of mistrust beyond well-known hisSome college/vocational 45 (29.20%) 28 (31.80%) school toric mistreatment of African Americans in research in a Bachelor’s degree 34 (22.10%) 9 (10.20%) sample of pediatric patients with Professional/graduate 16 (10.40%) 1 (1.10%) SCD and their caregivers. SCD school disproportionately affects racial/ Ever participated in research? ethnic minorities1; therefore, this Yes 95 (61.70%) 47 (53.40%) was a unique opportunity to systematically evaluate mistrust No 59 (38.30%) 41 (46.60%) to improve engagement in clinSCD genotype ical trials. Findings indicate that SS 92 (59.70%) 65 (73.90%) perceived stress, religious beliefs, and instrumental support are SC 42 (27.30%) 19 (21.60%) predictors of mistrust among SBþthal 20 (13.00%) 4 (4.50%) caregivers of children with SCD 4.67 (3.15) 6.97 (8.13) Healthcare utilization,a M (SD) and that gender and instrumental support are predictors of 0.22 (0.55) 0.44 (0.93) Number of health complications,b M (SD) mistrust among AYAs with SCD. c,d Higher caregiver perceived 1.83 (1.96) 2.35 (2.04) Mistrust score, M (SD) stress, a proximal social ecologic 3.42 (1.05) 3.31 (1.18) Social support score,d M (SD) factor, was found to significantly Instrumental support score,d 5.32 (1.74) 5.19 (1.78) contribute to greater mistrust, M (SD) consistent with prior work, a Total number of daily medications, treatments, and hospitalizations in the past year. revealing the same relationship b Total number of medical and psychosocial diagnoses. c Mistrust scores were skewed and thus transformed using the square root transformation (caregiver for caregivers of children with M¼1.09, SD¼0.80; adolescent and young adult M¼1.32, SD¼0.78). SCD or asthma.25 Although not d There were no significant differences between caregivers and adolescent and young adults with sickle a primary finding of this study, cell disease. SCD, sickle cell disease. associations were identified for education level with perceived gender and instrumental support explained 18% of the stress, and monthly household income with perceived variance in mistrust (full model, F[2,85]¼4.88, R2¼0.18, stress, suggesting that among this sample, stress was p¼0.000). associated with lower SES. This association likely impacts Other
9 (5.90%)
1 (1.10%)
www.ajpmonline.org
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
Table 3. Correlates of Mistrust of Clinical Trials Research (Spearman’s Rho Correlations)
Caregiver mistrust (n¼154)
Adolescent and young adult mistrust (n¼88)
Patient age
–0.05
–0.02
Participant gender
–0.05
–0.34***
Education level
–0.09
–0.06
Monthly household income
–0.12
0.04
SCD genotype
–0.07
0.04
Healthcare utilization
–0.11
0.07
Healthcare complications
–0.11
–0.09
Perceived stress
0.15†
–0.03
Instrumental support
0.18*
–0.25*
Social support
–0.06
–0.14
0.28***
0.14
Variables Proximal variables-demographics
Proximal variables-disease-related
Distal variables
Religious beliefs †
Note: Boldface indicates a trend relationship ( po0.10) or statistical significance (*po0.05; **po0.01; ***po0.001). SCD, sickle cell disease.
Table 4. Predictors of Mistrust of Clinical Trials Research (Hierarchical Regression Analyses) b
p-value
Perceived stress
0.05
0.028*
Perceived stress Religious beliefs Instrumental support
0.04 0.61 0.07
0.052* o0.001*** 0.044*
Participant gender
–0.55
o0.001***
Patient gender Instrumental support
–0.56 –0.11
o0.001*** 0.016*
Variables Caregivers (n¼154) Model summary 1 R2¼0.032 Adj. R2¼0.025 Sig¼0.028 Model summary 2 R2¼0.143 Adj. R2¼0.126 Sigo0.001 Adolescents and young adults (n¼88) Model summary 1 R2¼0.126 Adj. R2¼0.116 Sig¼0.001 Model summary 2 R2¼0.184 Adj. R2¼0.165 Sigo0.001
Note: Boldface indicates statistical significance (*po0.05; **po0.01; ***po0.001). Adj., adjusted; Sig, significance.
July 2016
S83
mistrust and decisions regarding clinical trials enrollment, but in indirect ways. Demographic and disease severity variables accounted for low percentage of variance in mistrust, despite having sufficient power to detect small to medium effects; thus, the relationship of demographics or SCD severity with mistrust is likely complex. Further, the role of perceived stress in mistrust may not be exclusive to the SCD community, but rather an indication of mistrust across racial/ethnic minorities. Researchers have tried to address SES-related difficulties by offering instrumental support or incentives to decrease barriers and encourage enrollment; however, present findings reveal that greater instrumental support is associated with greater mistrust for caregivers. Caregivers may believe that researchers attempt to buy their participation by offering incentives or increase the amount of incentives to mask the risks of participation. In addition, the role of greater instrumental support in mistrust may also be the result of a psychological phenomenon known as “stereotype threat,”39 aroused when a patient is aware of belonging to a negatively stereotyped group, evaluates cues where the stereotype is relevant, and ultimately becomes dissatisfied with healthcarerelated interactions.40 For SCD, instrumental support used to encourage enrollment may elicit greater mistrust, as these predominantly racial/ ethnic minority communities
S84
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
may feel that acceptance of incentives confirms negative stereotypes. Future studies are needed to evaluate stereotype threat in the context of disparities in research participation. Religious beliefs countering medical science, a community-level social ecologic factor, was identified as a predictor of greater mistrust among caregivers of children with SCD. Although assessed with only two items, this finding is consistent with published studies14,34,35 that have noted the significance of religion among racial/ethnic minorities, the belief that disease-related outcomes are under the control of God, and the relationship between religion and clinical trials participation. Researchers have taken into account the role of religiosity and have included religious institutions as effective venues for health-based programs and clinical trials enrollment.41,42 However, it is important to consider religious institutions not only as means to encouraging clinical trials participation but also as trusted sources for disseminating general health information. Encouraging religious institutions and leaders to understand the importance of health promotion may increase the likelihood of researchers gaining community acceptance and breaking down mistrust. Factors that influence mistrust for AYAs with SCD vary from those of caregivers. The most proximal factor contributing to AYA mistrust was gender. Male AYAs with SCD were found to have significantly greater mistrust than female AYAs. Male African Americans are underrepresented in biomedical research, and a lack of trust has been noted as the primary source.32,43 When they do participate, they are motivated by civic duty, personal or family history of the disease, and compensation.32 Compensation (e.g., money and gifts) was an incentive captured on the measure of instrumental support; however, unlike caregivers, use of fewer incentives in research contributed to greater mistrust among AYAs. This finding is not surprising; AYAs endorse the use of incentives during recruitment and retention strategies.31 The AYAs in this study, having had a chronic health condition throughout their lifetimes, may feel that participating in SCD research is less of a risk and that incentives are a greater benefit. Additionally, they may not consider the use of incentives as a stereotype threat. Based on these findings, researchers should approach the use of incentives with caution and sensitivity, particularly in studies where parental permission for child participation is needed, given how instrumental support differs across AYAs and caregivers in terms of mistrust.
Limitations These findings are subject to potential limitations. First, mistrust is one among a number of perceived barriers that may deter enrollment in clinical trials research. Others include study design and logistics (e.g., time and location of
study site)19,25,26,44; however, the decision to further evaluate factors related to mistrust of research beyond historic mistreatment of racial/ethnic minorities was warranted based on preliminary findings and lack of current literature in this area. Second, this analysis was conducted with a mistrust measure with only initial support for its validity. There are several clinically validated scales that measure mistrust,44–49 but most measure mistrust within the context of the healthcare system and not clinical trials, are not theoretically derived, or have not been validated in a sample of patients with chronic health conditions. Future studies may use one of these scales in addition to the PRPQ to measure mistrust as it relates to decisions about participating in clinical trials. Lastly, the participants were recruited primarily from comprehensive pediatric sickle cell centers where exposure to research is more prevalent. Thus, predictors of mistrust may be different in patients treated by providers in the community, patients who declined participating in the parent study, and patients with other chronic health conditions that may not expose them to frequent interactions within the healthcare system.
Conclusions Despite these limitations, information from this study may allow researchers to address both proximal and distal factors related to mistrust through recruitment, informed consent, and retention strategies; however, historic contributions cannot and should not be diminished or viewed as a less important cause of mistrust. One such strategy that has been effective in prior work among children with SCD and families could include the use of a patient navigator to address the identified social ecologic factors associated with mistrust, among other barriers to participation, while educating on the potential benefits in order to improve the decision-making process.50 As the findings in this analysis have revealed, acknowledgement of religious beliefs and stressors related to SES, consideration for the appropriateness and types of incentives, and tailoring research and informed consent processes for specific subgroups may reduce the disparities in research participation and ultimately improve SCD treatments and outcomes. Publication of this article was supported by the Centers for Disease Control and Prevention. This study was funded by a grant from the National Center for Minority Health and Health Disparities (1RC1MD004418). Chavis A. Patterson, PhD, was previously affiliated with St. Christopher’s Hospital for Children/Drexel University School of Medicine, Philadelphia, Pennsylvania. Lamia P. Barakat, PhD, was previously affiliated with Drexel University, Philadelphia, Pennsylvania.
www.ajpmonline.org
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
References 1. National Heart, Lung, and Blood Institute. Evidence Based Management of SCD. www.nhlbi.nih.gov/sites/www.nhlbi.nih.gov/files/sicklecell-disease-report.pdf. Published 2014. Accessed January 23, 2016. 2. Hankins J, Wang W. The painful face of poverty. Pediatr Blood Cancer. 2009;52(2):157–158. http://dx.doi.org/10.1002/pbc.21856. 3. Price JH, Khubchandani J, McKinney M, Braun R. Racial/ethnic disparities in chronic diseases of youths and access to health care in the United States. Biomed Res Int. 2013;2013(1):1–12. http://dx.doi. org/10.1155/2013/787616. 4. Brandow AM, Brousseau DC, Pajewski NM, Panepinto JA. Vasoocclusive painful events in sickle cell disease: impact on child wellbeing. Pediatr Blood Cancer. 2010;54(1):92–97. http://dx.doi.org/ 10.1002/pbc.22222. 5. Edwards CL, Scales MT, Loughlin C, et al. A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease. Int J Behav Med. 2005;12(3):171–179. http://dx.doi.org/ 10.1207/s15327558ijbm1203_6. 6. Raphael JL, Shetty PB, Liu H, Mahoney DH, Mueller BU. A critical assessment of transcranial doppler screening rates in a large pediatric sickle cell center: opportunities to improve healthcare quality. Pediatr Blood Cancer. 2008;51(5):647–651. http://dx.doi.org/10.1002/ pbc.21677. 7. Robinson MR, Daniel LC, O’Hara EA, Szabo MM, Barakat LP. Insurance status as a sociodemographic risk factor for functional outcomes and health-related quality of life among youth with sickle cell disease. J Pediatr Hematol Oncol. 2014;36(1):51–56. http://dx.doi.org/ 10.1097/MPH.0000000000000013. 8. Paskett ED, Reeves KW, McLaughlin JM, et al. Recruitment of minority and underserved populations in the United States: the Centers for Population Health and Health Disparities experience. Contemp Clin Trials. 2008;29(6):847–861. http://dx.doi.org/10.1016/j. cct.2008.07.006. 9. Lebensburger JD, Hilliard LM, Pair LE, Oster R, Howard TH, Cutter GR. Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov. Clin Trials. 2015;12(6):575–583. http://dx.doi.org/ 10.1177/1740774515590811. 10. George S, Duran N, Norris K. A systematic review of barriers and facilitators to minority research participation among African Americans, Latinos, Asian Americans, and Pacific Islanders. Am J Public Health. 2014;104(2):e16–e31. http://dx.doi.org/10.2105/ AJPH.2013.301706. 11. Benkert R, Peters RM, Clark R, Keves-Foster K. Effects of perceived racism, cultural mistrust and trust in providers on satisfaction with care. J Natl Med Assoc. 2006;98(9):1532–1540. 12. Katz RV, Green BL, Kressin NR, Claudio C, Wang MQ, Russell SL. Willingness of minorities to participate in biomedical studies: confirmatory findings from a follow-up study using the Tuskegee Legacy Project Questionnaire. J Natl Med Assoc. 2007;99(9):1052–1060. 13. Thompson HS, Valdimarsdottir HB, Winkel G, Jandorf L, Redd W. The Group-Based Medical Mistrust Scale: psychometric properties and association with breast cancer screening. Prev Med. 2004;38(2):209– 218. http://dx.doi.org/10.1016/j.ypmed.2003.09.041. 14. Kibler JL, Brisco K. Evaluation of a brief questionnaire for assessing barriers to research participation. Ethn Dis. 2006;16(2):547–550. 15. Shavers VL, Lynch CF, Burmeister LF. Knowledge of the Tuskegee study and its impact on the willingness to participate in medical research studies. J Natl Med Assoc. 2000;92(12):563–572. 16. Freedman LS, Simon R, Foulkes MA, et al. Inclusion of women and minorities in clinical trials and the NIH Revitalization Act of 1993—the perspective of NIH clinical trialists. Control Clin Trials. 1995;16 (5):277–285; discussion 286–279, 293–309. 17. Geller SE, Koch A, Pellettieri B, Carnes M. Inclusion, analysis, and reporting of sex and race/ethnicity in clinical trials: have we made
July 2016
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
S85
progress? J Womens Health (Larchmt). 2011;20(3):315–320. http://dx. doi.org/10.1089/jwh.2010.2469. Chen MS Jr., Lara PN, Dang JH, Paterniti DA, Kelly K. Twenty years post-NIH Revitalization Act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials. Cancer. 2014;120(suppl 7): 1091–1096. http://dx.doi.org/10.1002/cncr.28575. Wynn L, Miller S, Faughnan L, et al. Recruitment of infants with sickle cell anemia to a Phase III trial: data from the BABY HUG study. Contemp Clin Trials. 2010;31(6):558–563. http://dx.doi.org/10.1016/j. cct.2010.08.007. Roberts DO, Covert B, Rodeghier MJ, et al. Randomization is not associated with socio-economic and demographic factors in a multicenter clinical trial of children with sickle cell anemia. Pediatr Blood Cancer. 2014;61(9):1529–1535. http://dx.doi.org/10.1002/pbc.25072. Haywood C Jr., Lanzkron S, Bediako S, et al. Perceived discrimination, patient trust, and adherence to medical recommendations among persons with sickle cell disease. J Gen Intern Med. 2014;29(12):1657– 1662. http://dx.doi.org/10.1007/s11606-014-2986-7. Liem RI, Cole AH, Pelligra SA, Mason M, Thompson AA. Parental attitudes toward research participation in pediatric sickle cell disease. Pediatr Blood Cancer. 2010;55(1):129–133. http://dx.doi.org/10.1002/ pbc.22450. Omondi NA, Ferguson SE, Majhail NS, et al. Barriers to hematopoietic cell transplantation clinical trial participation of African American and black youth with sickle cell disease and their parents. J Pediatr Hematol Oncol. 2013;35(4):289–298. http://dx.doi.org/10.1097/MPH.0b013e3 1828d5e6a. Lebensburger JD, Sidonio RF, Debaun MR, Safford MM, Howard TH, Scarinci IC. Exploring barriers and facilitators to clinical trial enrollment in the context of sickle cell anemia and hydroxyurea. Pediatr Blood Cancer. 2013;60(8):1333–1337. http://dx.doi.org/10.1002/ pbc.24486. Barakat LP, Patterson CA, Mondestin V, et al. Initial development of a questionnaire evaluating perceived benefits and barriers to pediatric clinical trials participation. Contemp Clin Trials. 2013;34(2):218–226. http://dx.doi.org/10.1016/j.cct.2012.11.001. Patterson CA, Chavez V, Mondestin V, Deatrick J, Li Y, Barakat LP. Clinical trial decision-making in pediatric sickle cell disease: a qualitative study of perceived benefits and barriers to participation. J Pediatr Hematol Oncol. 2014;37(6):415–422. http://dx.doi.org/ 10.1097/MPH.0000000000000216. Kazak AE. A contextual family/systems approach to pediatric psychology: introduction to the special issue. J Pediatr Psychol. 1997;22(2): 141–148. http://dx.doi.org/10.1093/jpepsy/22.2.141. Gil KM, Carson JW, Porter LS, et al. Daily stress and mood and their association with pain, health-care use, and school activity in adolescents with sickle cell disease. J Pediatr Psychol. 2003;28(5):363– 373. http://dx.doi.org/10.1093/jpepsy/jsg026. Porter LS, Gil KM, Carson JW, Anthony KK, Ready J. The role of stress and mood in sickle cell disease pain: an analysis of daily diary data. J Health Psychol. 2000;5(1):53–63. http://dx.doi.org/10.1177/ 135910530000500109. Support & Social Conflict: Section One—Social Support. Psychosocial Notebook 2008. www.macses.ucsf.edu/research/psychosocial/socsupp. php. Accessed December 15, 2015. Jones FC, Broome ME. Focus groups with African American adolescents: enhancing recruitment and retention in intervention studies. J Pediatr Nurs. 2001;16(2):88–96. http://dx.doi.org/10.1053/ jpdn.2001.23151. Byrd GS, Edwards CL, Kelkar VA, et al. Recruiting intergenerational African American males for biomedical research studies: a major research challenge. J Natl Med Assoc. 2011;103(6):480–487. http://dx. doi.org/10.1016/S0027-9684(15)30361-8.
S86
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
33. Rothmier JD, Lasley MV, Shapiro GG. Factors influencing parental consent in pediatric clinical research. Pediatrics. 2003;111(5, pt 1): 1037–1041. http://dx.doi.org/10.1542/peds.111.5.1037. 34. Daverio-Zanetti S, Schultz K, del Campo MA, Malcarne V, Riley N, Sadler GR. Is religiosity related to attitudes toward clinical trials participation? J Cancer Educ. 2015;30(2):220–224. http://dx.doi.org/ 10.1007/s13187-014-0696-9. 35. Rivers D, August EM, Sehovic I, Lee Green B, Quinn GP. A systematic review of the factors influencing African Americans’ participation in cancer clinical trials. Contemp Clin Trials. 2013;35(2):13–32. http://dx. doi.org/10.1016/j.cct.2013.03.007. 36. Pullen E, Perry B, Oser C. African American women’s preventative care usage: the role of social support and racial experiences and attitudes. Sociol Health Illn. 2014;36(7):1037–1053. http://dx.doi.org/ 10.1111/1467-9566.12141. 37. George LK, Ellison CG, Larson DB. Explaining the relationships between religious involvement and health. Psychol Inquiry. 2002;13:190–200. http://dx.doi.org/10.1207/S15327965PLI1303_04. 38. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385–396. http://dx.doi.org/10.2307/2136404. 39. Steele CM, Aronson J. Stereotype threat and the intellectual test performance of African Americans. J Pers Soc Psychol. 1995;69(5): 797–811. http://dx.doi.org/10.1037/0022-3514.69.5.797. 40. Aronson J, Burgess D, Phelan SM, Juarez L. Unhealthy interactions: the role of stereotype threat in health disparities. Am J Public Health. 2013;103(1):50–56. http://dx.doi.org/10.2105/AJPH.2012.300828. 41. Frew PM, Omer SB, Parker K, et al. Delivering a “dose of hope”: a faithbased program to increase older African Americans’ participation in clinical trials. JMIR Res Protoc. 2015;4(2):e64. http://dx.doi.org/10. 2196/resprot.4072.
42. DeHaven MJ, Hunter IB, Wilder L, Walton JW, Berry J. Health programs in faith-based organizations: are they effective? Am J Public Health. 2004;94(6):1030–1036. http://dx.doi.org/10.2105/AJPH.94.6. 1030. 43. Diaz VA, Mainous AG 3rd, McCall AA, Geesey ME. Factors affecting research participation in African American college students. Fam Med. 2008;40(1):46–51. 44. Kennedy BM, Burnett MF. Clinical research trials: factors that influence and hinder participation. J Cult Divers. 2007;14(3):141–147. 45. Shelton RC, Winkel G, Davis SN, et al. Validation of the groupbased medical mistrust scale among urban black men. J Gen Intern Med. 2010;25(6):549–555. http://dx.doi.org/10.1007/ s11606-010-1288-y. 46. Anderson LA, Dedrick RF. Development of the Trust in Physician Scale: a measure to assess interpersonal trust in patient-physician relationships. Psychol Rep. 1990;67(3, pt 2):1091–1100. http://dx.doi. org/10.2466/pr0.1990.67.3f.1091. 47. Rose A, Peters N, Shea JA, Armstrong K. Development and testing of the health care system distrust scale. J Gen Intern Med. 2004;19(1): 57–63. http://dx.doi.org/10.1111/j.1525-1497.2004.21146.x. 48. Zheng B, Hall MA, Dugan E, Kidd KE, Levine D. Development of a scale to measure patients’ trust in health insurers. Health Serv Res. 2002;37(1):187–202. 49. Hall MA, Camacho F, Dugan E, Balkrishnan R. Trust in the medical profession: conceptual and measurement issues. Health Serv Res. 2002;37(5):1419–1439. http://dx.doi.org/10.1111/1475-6773.01070. 50. Daniel LC, Li Y, Smith K, et al. Lessons learned from a randomized controlled trial of a family-based intervention to promote school functioning for school-age children with sickle cell disease. J Pediatr Psychol. 2015;40(10):1085–1094. http://dx.doi.org/10.1093/jpepsy/jsv063.
www.ajpmonline.org
Methods: Over an 18-month period (2009–2010), participants completed questionnaires of perceived barriers and benefits to clinical trials enrollment, perceived stress, and self-reported demographic and disease-related information. Analyses (January–June 2015) used multivariable linear regressions to evaluate predictors of mistrust. Results: Data were analyzed for 154 caregivers (mean age, 38.75 years; SD¼9.56 years; 90.30% female) and 88 AYAs (mean age, 24.76 years; SD¼7.25 years; 46.40% female). Among caregivers (full model, R2¼0.14, pr0.001), greater mistrust was explained by higher perceived stress (β¼0.04, p¼0.052); religious beliefs (β¼0.61, pr0.001); and greater instrumental support (β¼0.07, p¼0.044). Among AYAs (full model, R2¼0.18, pr0.001), higher mistrust was explained by being male (β¼–0.56, pr0.001) and lower instrumental support (β¼–0.11, p¼0.016). Mistrust was significantly greater among caregivers that reported no prior involvement in medical research (p¼0.003). Conclusions: By understanding the complexity through which social ecologic factors contribute to mistrust, researchers may create targeted strategies to address mistrust and increase engagement in SCD research for caregivers and AYAs. (Am J Prev Med 2016;51(1S1):S78–S86) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
S
ickle cell disease (SCD) affects approximately 70,000–100,000 Americans and is one of the most common chronic conditions affecting primarily racial and ethnic minorities (e.g., African ancestry, Hispanic, Mediterranean, and Asian descent).1–3 Relatedly, many factors contribute to health disparities seen in SCD, From the 1The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; and 2Perelman School of Medicine of The University of Pennsylvania, Philadelphia, Pennsylvania Address correspondence to: Evelyn M. Stevens, MPH, The Children’s Hospital of Philadelphia, 3501 Civic Center Boulevard, Colket Translational Research Building 10300-06, Philadelphia PA 19104. E-mail: [email protected]. This article is part of the supplement issue titled Developing a Unified Approach for Sickle Cell Disease. 0749-3797/$36.00 http://dx.doi.org/10.1016/j.amepre.2016.01.024
including disproportionate percentages of these populations living in poverty and having limited access to specialized care.2–7 The conduct of therapeutic clinical trials to evaluate the feasibility, acceptability, and efficacy of new treatments and technologies among diverse samples is critical to decreasing health disparities and improving long-term health outcomes.8 A recent review revealed that 25 (14%) of the 174 SCD clinical investigations registered with ClinicalTrials.gov were terminated or withdrawn owing to low enrollment, suggesting a need for researchers to continue evaluation of racial/ethnic minorities’ attitudinal beliefs about SCD clinical trials research.9 Mistrust of research, defined through two concepts, cultural mistrust (suspicion of European Americans based on history of racism and unfair treatment) and medical mistrust (overall distrust of the healthcare system), is a frequently cited barrier accounting for
S78 Am J Prev Med 2016;51(1S1):S78–S86 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
overall satisfaction with care and inadequate enrollment of minorities in clinical trials.10–14 Mistrust is often linked to historic misconduct with minorities in research, particularly exploitation of African Americans in medical research (i.e., Tuskegee Syphilis Study).12,15 Although federal guidelines were developed over the past two decades to improve representation of disenfranchised populations in research,16 mistrust is still prevalent and minorities remain under-represented in clinical trials research.8,17,18 Studies among pediatric patients with SCD and their caregivers have focused on barriers to clinical trials enrollment, including study design and practical considerations (i.e., time and demands).19,20 Limited literature highlights mistrust of research as a significant barrier to clinical trials enrollment among the SCD community.21– 24 Most of these studies used qualitative data gathered through focus groups of pediatric patients and their caregivers and were limited by small sample sizes, evaluated attitudes toward enrollment in a specific clinical trial, or evaluated attitudes toward the amount of SCD research conducted as opposed to perceived benefits and barriers toward research.22–24 Additionally, none evaluated factors related to mistrust of research. More effective redress of the barrier of mistrust requires increased understanding of disease-related and psychosocial contributors, which will allow researchers to frame SCD research in a manner that gains community acceptance and increases informed consent. Relevant to this effort, prior work systematically evaluated perceived benefits and barriers of pediatric clinical trials enrollment for SCD and asthma patients and their caregivers based on The Social Ecologic Model.25,26 The social ecology of children with chronic health conditions describes multiple, bidirectional influences on a child and family’s adaptation to the chronic condition. These influences, from proximal to distal variables and organized at each level of a child’s social ecology, are patient, caregiver and family, community, and society/culture.27 Factors affecting research participation may connect to factors influencing mistrust. For example, perceived severity of a child’s illness (a patientlevel variable) has been noted as a factor affecting parents’ willingness to allow their child to participate in research.19 Disease severity can increase stress and anxiety among caregivers and patients, particularly in families that are challenged with management of SCDrelated complications,28,29 and an association between perceived stress and greater mistrust among caregivers of children with SCD and asthma has been established.25 Additionally, minorities may experience stress related to economic difficulties (a family-level variable). Researchers have made attempts to reduce SES-related July 2016
S79
barriers to research participation by offering instrumental support, or tangible and physical support provided to assist people with participating in a clinical trial (e.g., compensation, transportation, child care, access to care).30 Successful use of these supports to encourage participation in clinical trials has been mixed, with some suggesting incentives are an effective recruitment strategy and others noting that incentives have no impact on parents’ decisions to enroll their child in research.31–33 Other factors that influence minority research participation, potentially contributing to mistrust of research, include religious beliefs countering medical science14,34,35 and social supports (e.g., family and friends support research participation).25 Minority families have strong religious beliefs and supportive social networks that are often extremely important within their community. Although medical decision making and healthcare utilization are often influenced by religion and social networks (a society/culture variable),36,37 it is unclear how and to what extent religion and social support influence mistrust. The purpose of this study was to evaluate proximal (age, gender, disease severity, perceived stress, and SES) and distal (religious beliefs, social support, and instrumental support) social ecologic factors as contributors to mistrust among caregivers of children with SCD and adolescents and young adults (AYAs) with SCD. It was hypothesized that greater disease severity, greater perceived stress, religious beliefs countering medical science, and lower social and instrumental support would be associated with greater mistrust of research and having an older child or being an older AYA, being male, and having lower SES would be associated with greater mistrust. Furthermore, greater mistrust was expected to be associated with no prior involvement in research.
Methods This study was performed using data from a multisite study, which evaluated perceived benefits and barriers to pediatric clinical trials participation through development and initial validation of the Pediatric Research Participation Questionnaire (PRPQ).25,26 The PRPQ was developed in four phases that included item generation from the project team, community partners, and SCD medical experts; tailoring of the items for caregivers and for AYAs and children with SCD or asthma; review of the measure by stakeholders; and pilot testing to ensure clarity and ease of administration. The study protocol was approved by the appropriate IRBs. Data were collected over an 18-month period in 2009–2010. An exploratory factor analysis was conducted to identify latent structures of the questionnaire of which mistrust of research/ researchers was identified as a primary consideration affecting decisions to participate in clinical trials.25
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
S80
Study Sample
Measures
In the parent study, 296 of 385 (77.1%) consented to participate; 20.1% (n¼78) refused participation; and 2.8% (n¼11) did not meet inclusion criteria. Reasons for refusal are described elsewhere.25 For this secondary analysis, only caregivers of children with SCD (n¼154) and AYAs (aged Z16 years) with SCD (n¼88) were included. Participants were recruited from East Coast pediatric SCD centers and an adult outpatient clinic associated with the medical universities that provided care for many AYA patients that transitioned out of pediatric care. All participants completed the PRPQ on paper and in private during clinic appointments. A research assistant was available to address health literacy issues. The PRPQ assessed attitudes (with a binary response category of agree or disagree) toward medical and psychosocial research studies to aid in understanding decision making about clinical trials enrollment.
Mistrust of research/researchers, social support, and instrumental support (tangible or physical support offered to encourage trial participation) were factors identified in the exploratory factor analysis of the PRPQ as contributors to clinical trials enrollment decisions. The items that loaded on these factors were used to compute a total score, with higher scores indicating greater levels of mistrust, social support, and instrumental support (Table 1). Reliability was adequate for each of these variables among caregivers and AYAs (mistrust, α¼0.70 and α¼0.66; social support, α¼0.76 and α¼0.80; instrumental support, α¼0.70 and α¼0.68; respectively). Religious beliefs were assessed through one item of the PRPQ that reads: Researchers sometimes undermine the power of God and God’s will. In addition, one item of the social support scale asked participants if their religious leader would want me/my child to be in research (Table 1).
Table 1. Study Measures Mistrust of research/researchers Total score of the following items: 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11)
We participate in research because the healthcare team takes good care of my childa The government sometimes exposes research participants to medicine and procedures known to be harmful to one’s healtha Research is a part of a conspiracy to harm minority groups We are willing to participate in research when we know exactly what we will be asked to doa The healthcare team will view me/my child only as a research participant if I enroll The healthcare team will treat me/my child differently if I enroll When the researcher is of the same race I am more likely to participate Researchers sometimes hide information from participants prior to research Researchers ask for financial information that may get back to the government and cause me to lose my check/benefits Personal information given in research does not stay private and might hurt me/people I care about Researchers are motivated by their own career goals and not the welfare of their participants
Social support of research participation Total score of the following items: 1) 2) 3) 4)
My family would want me/my child to be in research My friends would want me/my child to be in research My religious leader would want me/my child to be in research My community agency would want me/my child to be in research
Instrumental support for research Total score of the following items: 1) 2) 3) 4) 5) 6) 7)
I/We would participate in research if we could learn more about my/my child’s illness I/We would participate in research if we could get tests/medicine my insurance won’t cover I/We would participate in research if we could get tests or medicine not available to the public More people would participate in research if researchers provide childcare More people would participate in research if researchers provide money or gifts More people would participate in research if researchers cover transportation costs More people would participate in research if researchers provide telephone/internet participation
Religious beliefs Endorsement of the following item: 1) Researchers sometimes undermine the power of God and God’s will. 2) My religious leader would want me/my child to be in research. Note: All items were derived from the Pediatric Research Participation Questionnaire (PRPQ) and loaded on one of the four-factor structures that were identified during an exploratory factor analysis of the PRPQ (Barakat et al., 2013).25 a Items did not load on the mistrust factor of the PRPQ but were added to mistrust measure because they were identified as barriers to research participation related to mistrust. The addition of these items resulted in greater reliability.
www.ajpmonline.org
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
S81
The Perceived Stress Scale four-item short form of the 14-item measure evaluated the degree to which participants perceived their lives as stressful. The Perceived Stress Scale showed acceptable reliability in prior validation studies.38 Reliability was adequate for caregivers (α¼0.66) and marginal for AYAs (α¼0.53).25 Participants completed a General Information Form to collect demographic and disease-related information and prior involvement in medical research (coded as yes/no). Disease severity was assessed by SCD genotype; healthcare utilization (total number of daily medications, treatments, and hospitalizations in the past year); and SCD complications (total number of medical and psychosocial diagnoses). Demographics included age of child/ AYA with SCD, gender of caregiver or AYA completing the questionnaire, education level of caregiver or AYA, and monthly household income.
Statistical Analysis Analyses were conducted separately for caregivers and AYAs during January–July 2015. Descriptive statistics were computed for all study variables checking for outliers and distribution. Fisher exact tests, t-tests, Spearman correlations, and linear regressions were used for hypothesis testing. All variables correlated with mistrust (pr0.10) were included in the linear regression models. Hierarchical linear regression models were computed based on the Social Ecologic Model from proximal to more distal—patientand family-level variables on the first step (demographics, disease severity, perceived stress, and SES) and community-level variables on the second step (instrumental support, beliefs about religion, and social support) (Figure 1). A two-sided p-value o0.05 was considered statistically significant for hypothesis testing. Power was 40.80 for detecting medium effects with 0.05 Type I error. All of the analyses were performed in SPSS, version 22.
Results
Figure 1. Factors related to mistrust of clinical trials research: social ecologic framework.
Participants included 154 caregivers (mean age, 38.75 years; SD¼9.56 years) and 88 AYAs (mean age, 24.76 years; SD¼7.25 years) (Table 2). Majority of caregivers and AYAs self-identified as Black or African American (caregivers, 92.20%; AYAs, 96.60%) and all participants self-identified as Non-Hispanic/Latino. SCD genotype SS was most common among AYAs (73.90%) and the children of the caregivers (59.70%). Mistrust, instrumental support, and social support scores did not differ significantly between caregivers and AYAs. Among caregivers, greater instrumental support (r ¼0.18, p¼0.02) and religious beliefs countering medical science (r¼0.28, pr0.000) were significantly correlated with greater mistrust of research (Table 3). There was a trend toward significance for higher perceived stress with greater mistrust among caregivers (r¼0.15, p¼0.069). Among AYAs, lower instrumental support was significantly correlated with lower mistrust (r¼–0.25, p¼0.19). Mistrust differed significantly between female AYAs (mean¼1.03, SD¼0.79) and male AYAs (mean¼1.58, SD¼0.69, pr0.001). Variables found to be associated with mistrust (po0.10) for
caregivers (perceived stress, religious beliefs, and instrumental support) and AYAs (gender and instrumental support) were further evaluated as predictors of mistrust in regression analyses. For caregivers, higher perceived stress contributed significantly to greater mistrust (β¼0.05, p¼0.028) (Table 4). Religious beliefs and instrumental support were added to the model and were also identified as significant predictors of mistrust (β¼0.61, p¼0.000 and β¼0.07, p¼0.044, respectively), such that religious beliefs countering medical science and greater instrumental support predicted greater mistrust among caregivers. Collectively, perceived stress, religious beliefs, and instrumental support explained 14% of the variation in mistrust (full model, F[3,148]¼8.24, R2¼0.14, p¼0.000). Among AYAs, patient gender contributed significantly to mistrust, with male AYAs having greater mistrust as compared with female AYAs (β¼–0.55, p¼0.000). Instrumental support was also a significant independent predictor of greater mistrust (β¼–0.11, p¼0.016). Both
July 2016
S82
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
Table 2. Participant Demographic, Medical, and Summary Score Characteristics
Demographics
Caregiver, n (%) (n¼154)
Adolescent and young adult, n (%) (n¼88)
139 (90.30%)
41 (46.60%)
15 (9.70%)
47 (53.40%)
38.75 (9.56)
24.76 (7.25)
154 (100.00%)
88 (100.00%)
142 (92.20%)
85 (96.60%)
3 (1.90%)
2 (2.30%)
Gender Female Male Age (years), M (SD) Ethnicity Non-Hispanic/Latino
Mistrust was significantly greater in caregivers that reported no prior involvement in medical research (mean¼1.33, SD¼0.77) compared with caregivers that reported prior involvement (mean¼0.94, SD¼0.79, t[152]¼3.02, p¼0.003, d¼0.51). There was no significant difference in mistrust based on prior involvement in medical research for AYAs.
Race Black or African American White
Discussion
Mistrust has been cited as a barrier to clinical trials enrollEducation ment among the SCD communSome high school 11 (7.10%) 27 (30.70%) ity.21–24 This study is among the High school graduate 48 (31.20%) 23 (26.10%) first to evaluate factors of mistrust beyond well-known hisSome college/vocational 45 (29.20%) 28 (31.80%) school toric mistreatment of African Americans in research in a Bachelor’s degree 34 (22.10%) 9 (10.20%) sample of pediatric patients with Professional/graduate 16 (10.40%) 1 (1.10%) SCD and their caregivers. SCD school disproportionately affects racial/ Ever participated in research? ethnic minorities1; therefore, this Yes 95 (61.70%) 47 (53.40%) was a unique opportunity to systematically evaluate mistrust No 59 (38.30%) 41 (46.60%) to improve engagement in clinSCD genotype ical trials. Findings indicate that SS 92 (59.70%) 65 (73.90%) perceived stress, religious beliefs, and instrumental support are SC 42 (27.30%) 19 (21.60%) predictors of mistrust among SBþthal 20 (13.00%) 4 (4.50%) caregivers of children with SCD 4.67 (3.15) 6.97 (8.13) Healthcare utilization,a M (SD) and that gender and instrumental support are predictors of 0.22 (0.55) 0.44 (0.93) Number of health complications,b M (SD) mistrust among AYAs with SCD. c,d Higher caregiver perceived 1.83 (1.96) 2.35 (2.04) Mistrust score, M (SD) stress, a proximal social ecologic 3.42 (1.05) 3.31 (1.18) Social support score,d M (SD) factor, was found to significantly Instrumental support score,d 5.32 (1.74) 5.19 (1.78) contribute to greater mistrust, M (SD) consistent with prior work, a Total number of daily medications, treatments, and hospitalizations in the past year. revealing the same relationship b Total number of medical and psychosocial diagnoses. c Mistrust scores were skewed and thus transformed using the square root transformation (caregiver for caregivers of children with M¼1.09, SD¼0.80; adolescent and young adult M¼1.32, SD¼0.78). SCD or asthma.25 Although not d There were no significant differences between caregivers and adolescent and young adults with sickle a primary finding of this study, cell disease. SCD, sickle cell disease. associations were identified for education level with perceived gender and instrumental support explained 18% of the stress, and monthly household income with perceived variance in mistrust (full model, F[2,85]¼4.88, R2¼0.18, stress, suggesting that among this sample, stress was p¼0.000). associated with lower SES. This association likely impacts Other
9 (5.90%)
1 (1.10%)
www.ajpmonline.org
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
Table 3. Correlates of Mistrust of Clinical Trials Research (Spearman’s Rho Correlations)
Caregiver mistrust (n¼154)
Adolescent and young adult mistrust (n¼88)
Patient age
–0.05
–0.02
Participant gender
–0.05
–0.34***
Education level
–0.09
–0.06
Monthly household income
–0.12
0.04
SCD genotype
–0.07
0.04
Healthcare utilization
–0.11
0.07
Healthcare complications
–0.11
–0.09
Perceived stress
0.15†
–0.03
Instrumental support
0.18*
–0.25*
Social support
–0.06
–0.14
0.28***
0.14
Variables Proximal variables-demographics
Proximal variables-disease-related
Distal variables
Religious beliefs †
Note: Boldface indicates a trend relationship ( po0.10) or statistical significance (*po0.05; **po0.01; ***po0.001). SCD, sickle cell disease.
Table 4. Predictors of Mistrust of Clinical Trials Research (Hierarchical Regression Analyses) b
p-value
Perceived stress
0.05
0.028*
Perceived stress Religious beliefs Instrumental support
0.04 0.61 0.07
0.052* o0.001*** 0.044*
Participant gender
–0.55
o0.001***
Patient gender Instrumental support
–0.56 –0.11
o0.001*** 0.016*
Variables Caregivers (n¼154) Model summary 1 R2¼0.032 Adj. R2¼0.025 Sig¼0.028 Model summary 2 R2¼0.143 Adj. R2¼0.126 Sigo0.001 Adolescents and young adults (n¼88) Model summary 1 R2¼0.126 Adj. R2¼0.116 Sig¼0.001 Model summary 2 R2¼0.184 Adj. R2¼0.165 Sigo0.001
Note: Boldface indicates statistical significance (*po0.05; **po0.01; ***po0.001). Adj., adjusted; Sig, significance.
July 2016
S83
mistrust and decisions regarding clinical trials enrollment, but in indirect ways. Demographic and disease severity variables accounted for low percentage of variance in mistrust, despite having sufficient power to detect small to medium effects; thus, the relationship of demographics or SCD severity with mistrust is likely complex. Further, the role of perceived stress in mistrust may not be exclusive to the SCD community, but rather an indication of mistrust across racial/ethnic minorities. Researchers have tried to address SES-related difficulties by offering instrumental support or incentives to decrease barriers and encourage enrollment; however, present findings reveal that greater instrumental support is associated with greater mistrust for caregivers. Caregivers may believe that researchers attempt to buy their participation by offering incentives or increase the amount of incentives to mask the risks of participation. In addition, the role of greater instrumental support in mistrust may also be the result of a psychological phenomenon known as “stereotype threat,”39 aroused when a patient is aware of belonging to a negatively stereotyped group, evaluates cues where the stereotype is relevant, and ultimately becomes dissatisfied with healthcarerelated interactions.40 For SCD, instrumental support used to encourage enrollment may elicit greater mistrust, as these predominantly racial/ ethnic minority communities
S84
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
may feel that acceptance of incentives confirms negative stereotypes. Future studies are needed to evaluate stereotype threat in the context of disparities in research participation. Religious beliefs countering medical science, a community-level social ecologic factor, was identified as a predictor of greater mistrust among caregivers of children with SCD. Although assessed with only two items, this finding is consistent with published studies14,34,35 that have noted the significance of religion among racial/ethnic minorities, the belief that disease-related outcomes are under the control of God, and the relationship between religion and clinical trials participation. Researchers have taken into account the role of religiosity and have included religious institutions as effective venues for health-based programs and clinical trials enrollment.41,42 However, it is important to consider religious institutions not only as means to encouraging clinical trials participation but also as trusted sources for disseminating general health information. Encouraging religious institutions and leaders to understand the importance of health promotion may increase the likelihood of researchers gaining community acceptance and breaking down mistrust. Factors that influence mistrust for AYAs with SCD vary from those of caregivers. The most proximal factor contributing to AYA mistrust was gender. Male AYAs with SCD were found to have significantly greater mistrust than female AYAs. Male African Americans are underrepresented in biomedical research, and a lack of trust has been noted as the primary source.32,43 When they do participate, they are motivated by civic duty, personal or family history of the disease, and compensation.32 Compensation (e.g., money and gifts) was an incentive captured on the measure of instrumental support; however, unlike caregivers, use of fewer incentives in research contributed to greater mistrust among AYAs. This finding is not surprising; AYAs endorse the use of incentives during recruitment and retention strategies.31 The AYAs in this study, having had a chronic health condition throughout their lifetimes, may feel that participating in SCD research is less of a risk and that incentives are a greater benefit. Additionally, they may not consider the use of incentives as a stereotype threat. Based on these findings, researchers should approach the use of incentives with caution and sensitivity, particularly in studies where parental permission for child participation is needed, given how instrumental support differs across AYAs and caregivers in terms of mistrust.
Limitations These findings are subject to potential limitations. First, mistrust is one among a number of perceived barriers that may deter enrollment in clinical trials research. Others include study design and logistics (e.g., time and location of
study site)19,25,26,44; however, the decision to further evaluate factors related to mistrust of research beyond historic mistreatment of racial/ethnic minorities was warranted based on preliminary findings and lack of current literature in this area. Second, this analysis was conducted with a mistrust measure with only initial support for its validity. There are several clinically validated scales that measure mistrust,44–49 but most measure mistrust within the context of the healthcare system and not clinical trials, are not theoretically derived, or have not been validated in a sample of patients with chronic health conditions. Future studies may use one of these scales in addition to the PRPQ to measure mistrust as it relates to decisions about participating in clinical trials. Lastly, the participants were recruited primarily from comprehensive pediatric sickle cell centers where exposure to research is more prevalent. Thus, predictors of mistrust may be different in patients treated by providers in the community, patients who declined participating in the parent study, and patients with other chronic health conditions that may not expose them to frequent interactions within the healthcare system.
Conclusions Despite these limitations, information from this study may allow researchers to address both proximal and distal factors related to mistrust through recruitment, informed consent, and retention strategies; however, historic contributions cannot and should not be diminished or viewed as a less important cause of mistrust. One such strategy that has been effective in prior work among children with SCD and families could include the use of a patient navigator to address the identified social ecologic factors associated with mistrust, among other barriers to participation, while educating on the potential benefits in order to improve the decision-making process.50 As the findings in this analysis have revealed, acknowledgement of religious beliefs and stressors related to SES, consideration for the appropriateness and types of incentives, and tailoring research and informed consent processes for specific subgroups may reduce the disparities in research participation and ultimately improve SCD treatments and outcomes. Publication of this article was supported by the Centers for Disease Control and Prevention. This study was funded by a grant from the National Center for Minority Health and Health Disparities (1RC1MD004418). Chavis A. Patterson, PhD, was previously affiliated with St. Christopher’s Hospital for Children/Drexel University School of Medicine, Philadelphia, Pennsylvania. Lamia P. Barakat, PhD, was previously affiliated with Drexel University, Philadelphia, Pennsylvania.
www.ajpmonline.org
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
References 1. National Heart, Lung, and Blood Institute. Evidence Based Management of SCD. www.nhlbi.nih.gov/sites/www.nhlbi.nih.gov/files/sicklecell-disease-report.pdf. Published 2014. Accessed January 23, 2016. 2. Hankins J, Wang W. The painful face of poverty. Pediatr Blood Cancer. 2009;52(2):157–158. http://dx.doi.org/10.1002/pbc.21856. 3. Price JH, Khubchandani J, McKinney M, Braun R. Racial/ethnic disparities in chronic diseases of youths and access to health care in the United States. Biomed Res Int. 2013;2013(1):1–12. http://dx.doi. org/10.1155/2013/787616. 4. Brandow AM, Brousseau DC, Pajewski NM, Panepinto JA. Vasoocclusive painful events in sickle cell disease: impact on child wellbeing. Pediatr Blood Cancer. 2010;54(1):92–97. http://dx.doi.org/ 10.1002/pbc.22222. 5. Edwards CL, Scales MT, Loughlin C, et al. A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease. Int J Behav Med. 2005;12(3):171–179. http://dx.doi.org/ 10.1207/s15327558ijbm1203_6. 6. Raphael JL, Shetty PB, Liu H, Mahoney DH, Mueller BU. A critical assessment of transcranial doppler screening rates in a large pediatric sickle cell center: opportunities to improve healthcare quality. Pediatr Blood Cancer. 2008;51(5):647–651. http://dx.doi.org/10.1002/ pbc.21677. 7. Robinson MR, Daniel LC, O’Hara EA, Szabo MM, Barakat LP. Insurance status as a sociodemographic risk factor for functional outcomes and health-related quality of life among youth with sickle cell disease. J Pediatr Hematol Oncol. 2014;36(1):51–56. http://dx.doi.org/ 10.1097/MPH.0000000000000013. 8. Paskett ED, Reeves KW, McLaughlin JM, et al. Recruitment of minority and underserved populations in the United States: the Centers for Population Health and Health Disparities experience. Contemp Clin Trials. 2008;29(6):847–861. http://dx.doi.org/10.1016/j. cct.2008.07.006. 9. Lebensburger JD, Hilliard LM, Pair LE, Oster R, Howard TH, Cutter GR. Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov. Clin Trials. 2015;12(6):575–583. http://dx.doi.org/ 10.1177/1740774515590811. 10. George S, Duran N, Norris K. A systematic review of barriers and facilitators to minority research participation among African Americans, Latinos, Asian Americans, and Pacific Islanders. Am J Public Health. 2014;104(2):e16–e31. http://dx.doi.org/10.2105/ AJPH.2013.301706. 11. Benkert R, Peters RM, Clark R, Keves-Foster K. Effects of perceived racism, cultural mistrust and trust in providers on satisfaction with care. J Natl Med Assoc. 2006;98(9):1532–1540. 12. Katz RV, Green BL, Kressin NR, Claudio C, Wang MQ, Russell SL. Willingness of minorities to participate in biomedical studies: confirmatory findings from a follow-up study using the Tuskegee Legacy Project Questionnaire. J Natl Med Assoc. 2007;99(9):1052–1060. 13. Thompson HS, Valdimarsdottir HB, Winkel G, Jandorf L, Redd W. The Group-Based Medical Mistrust Scale: psychometric properties and association with breast cancer screening. Prev Med. 2004;38(2):209– 218. http://dx.doi.org/10.1016/j.ypmed.2003.09.041. 14. Kibler JL, Brisco K. Evaluation of a brief questionnaire for assessing barriers to research participation. Ethn Dis. 2006;16(2):547–550. 15. Shavers VL, Lynch CF, Burmeister LF. Knowledge of the Tuskegee study and its impact on the willingness to participate in medical research studies. J Natl Med Assoc. 2000;92(12):563–572. 16. Freedman LS, Simon R, Foulkes MA, et al. Inclusion of women and minorities in clinical trials and the NIH Revitalization Act of 1993—the perspective of NIH clinical trialists. Control Clin Trials. 1995;16 (5):277–285; discussion 286–279, 293–309. 17. Geller SE, Koch A, Pellettieri B, Carnes M. Inclusion, analysis, and reporting of sex and race/ethnicity in clinical trials: have we made
July 2016
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
S85
progress? J Womens Health (Larchmt). 2011;20(3):315–320. http://dx. doi.org/10.1089/jwh.2010.2469. Chen MS Jr., Lara PN, Dang JH, Paterniti DA, Kelly K. Twenty years post-NIH Revitalization Act: enhancing minority participation in clinical trials (EMPaCT): laying the groundwork for improving minority clinical trial accrual: renewing the case for enhancing minority participation in cancer clinical trials. Cancer. 2014;120(suppl 7): 1091–1096. http://dx.doi.org/10.1002/cncr.28575. Wynn L, Miller S, Faughnan L, et al. Recruitment of infants with sickle cell anemia to a Phase III trial: data from the BABY HUG study. Contemp Clin Trials. 2010;31(6):558–563. http://dx.doi.org/10.1016/j. cct.2010.08.007. Roberts DO, Covert B, Rodeghier MJ, et al. Randomization is not associated with socio-economic and demographic factors in a multicenter clinical trial of children with sickle cell anemia. Pediatr Blood Cancer. 2014;61(9):1529–1535. http://dx.doi.org/10.1002/pbc.25072. Haywood C Jr., Lanzkron S, Bediako S, et al. Perceived discrimination, patient trust, and adherence to medical recommendations among persons with sickle cell disease. J Gen Intern Med. 2014;29(12):1657– 1662. http://dx.doi.org/10.1007/s11606-014-2986-7. Liem RI, Cole AH, Pelligra SA, Mason M, Thompson AA. Parental attitudes toward research participation in pediatric sickle cell disease. Pediatr Blood Cancer. 2010;55(1):129–133. http://dx.doi.org/10.1002/ pbc.22450. Omondi NA, Ferguson SE, Majhail NS, et al. Barriers to hematopoietic cell transplantation clinical trial participation of African American and black youth with sickle cell disease and their parents. J Pediatr Hematol Oncol. 2013;35(4):289–298. http://dx.doi.org/10.1097/MPH.0b013e3 1828d5e6a. Lebensburger JD, Sidonio RF, Debaun MR, Safford MM, Howard TH, Scarinci IC. Exploring barriers and facilitators to clinical trial enrollment in the context of sickle cell anemia and hydroxyurea. Pediatr Blood Cancer. 2013;60(8):1333–1337. http://dx.doi.org/10.1002/ pbc.24486. Barakat LP, Patterson CA, Mondestin V, et al. Initial development of a questionnaire evaluating perceived benefits and barriers to pediatric clinical trials participation. Contemp Clin Trials. 2013;34(2):218–226. http://dx.doi.org/10.1016/j.cct.2012.11.001. Patterson CA, Chavez V, Mondestin V, Deatrick J, Li Y, Barakat LP. Clinical trial decision-making in pediatric sickle cell disease: a qualitative study of perceived benefits and barriers to participation. J Pediatr Hematol Oncol. 2014;37(6):415–422. http://dx.doi.org/ 10.1097/MPH.0000000000000216. Kazak AE. A contextual family/systems approach to pediatric psychology: introduction to the special issue. J Pediatr Psychol. 1997;22(2): 141–148. http://dx.doi.org/10.1093/jpepsy/22.2.141. Gil KM, Carson JW, Porter LS, et al. Daily stress and mood and their association with pain, health-care use, and school activity in adolescents with sickle cell disease. J Pediatr Psychol. 2003;28(5):363– 373. http://dx.doi.org/10.1093/jpepsy/jsg026. Porter LS, Gil KM, Carson JW, Anthony KK, Ready J. The role of stress and mood in sickle cell disease pain: an analysis of daily diary data. J Health Psychol. 2000;5(1):53–63. http://dx.doi.org/10.1177/ 135910530000500109. Support & Social Conflict: Section One—Social Support. Psychosocial Notebook 2008. www.macses.ucsf.edu/research/psychosocial/socsupp. php. Accessed December 15, 2015. Jones FC, Broome ME. Focus groups with African American adolescents: enhancing recruitment and retention in intervention studies. J Pediatr Nurs. 2001;16(2):88–96. http://dx.doi.org/10.1053/ jpdn.2001.23151. Byrd GS, Edwards CL, Kelkar VA, et al. Recruiting intergenerational African American males for biomedical research studies: a major research challenge. J Natl Med Assoc. 2011;103(6):480–487. http://dx. doi.org/10.1016/S0027-9684(15)30361-8.
S86
Stevens et al / Am J Prev Med 2016;51(1S1):S78–S86
33. Rothmier JD, Lasley MV, Shapiro GG. Factors influencing parental consent in pediatric clinical research. Pediatrics. 2003;111(5, pt 1): 1037–1041. http://dx.doi.org/10.1542/peds.111.5.1037. 34. Daverio-Zanetti S, Schultz K, del Campo MA, Malcarne V, Riley N, Sadler GR. Is religiosity related to attitudes toward clinical trials participation? J Cancer Educ. 2015;30(2):220–224. http://dx.doi.org/ 10.1007/s13187-014-0696-9. 35. Rivers D, August EM, Sehovic I, Lee Green B, Quinn GP. A systematic review of the factors influencing African Americans’ participation in cancer clinical trials. Contemp Clin Trials. 2013;35(2):13–32. http://dx. doi.org/10.1016/j.cct.2013.03.007. 36. Pullen E, Perry B, Oser C. African American women’s preventative care usage: the role of social support and racial experiences and attitudes. Sociol Health Illn. 2014;36(7):1037–1053. http://dx.doi.org/ 10.1111/1467-9566.12141. 37. George LK, Ellison CG, Larson DB. Explaining the relationships between religious involvement and health. Psychol Inquiry. 2002;13:190–200. http://dx.doi.org/10.1207/S15327965PLI1303_04. 38. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385–396. http://dx.doi.org/10.2307/2136404. 39. Steele CM, Aronson J. Stereotype threat and the intellectual test performance of African Americans. J Pers Soc Psychol. 1995;69(5): 797–811. http://dx.doi.org/10.1037/0022-3514.69.5.797. 40. Aronson J, Burgess D, Phelan SM, Juarez L. Unhealthy interactions: the role of stereotype threat in health disparities. Am J Public Health. 2013;103(1):50–56. http://dx.doi.org/10.2105/AJPH.2012.300828. 41. Frew PM, Omer SB, Parker K, et al. Delivering a “dose of hope”: a faithbased program to increase older African Americans’ participation in clinical trials. JMIR Res Protoc. 2015;4(2):e64. http://dx.doi.org/10. 2196/resprot.4072.
42. DeHaven MJ, Hunter IB, Wilder L, Walton JW, Berry J. Health programs in faith-based organizations: are they effective? Am J Public Health. 2004;94(6):1030–1036. http://dx.doi.org/10.2105/AJPH.94.6. 1030. 43. Diaz VA, Mainous AG 3rd, McCall AA, Geesey ME. Factors affecting research participation in African American college students. Fam Med. 2008;40(1):46–51. 44. Kennedy BM, Burnett MF. Clinical research trials: factors that influence and hinder participation. J Cult Divers. 2007;14(3):141–147. 45. Shelton RC, Winkel G, Davis SN, et al. Validation of the groupbased medical mistrust scale among urban black men. J Gen Intern Med. 2010;25(6):549–555. http://dx.doi.org/10.1007/ s11606-010-1288-y. 46. Anderson LA, Dedrick RF. Development of the Trust in Physician Scale: a measure to assess interpersonal trust in patient-physician relationships. Psychol Rep. 1990;67(3, pt 2):1091–1100. http://dx.doi. org/10.2466/pr0.1990.67.3f.1091. 47. Rose A, Peters N, Shea JA, Armstrong K. Development and testing of the health care system distrust scale. J Gen Intern Med. 2004;19(1): 57–63. http://dx.doi.org/10.1111/j.1525-1497.2004.21146.x. 48. Zheng B, Hall MA, Dugan E, Kidd KE, Levine D. Development of a scale to measure patients’ trust in health insurers. Health Serv Res. 2002;37(1):187–202. 49. Hall MA, Camacho F, Dugan E, Balkrishnan R. Trust in the medical profession: conceptual and measurement issues. Health Serv Res. 2002;37(5):1419–1439. http://dx.doi.org/10.1111/1475-6773.01070. 50. Daniel LC, Li Y, Smith K, et al. Lessons learned from a randomized controlled trial of a family-based intervention to promote school functioning for school-age children with sickle cell disease. J Pediatr Psychol. 2015;40(10):1085–1094. http://dx.doi.org/10.1093/jpepsy/jsv063.
www.ajpmonline.org