Clinical Trial Decision-making among AYA with Cancer

Approximately 21,400 adolescents and young adults (AYA) ages 15 to 29 years were diagnosed with cancer in 2000, which is nearly 3 times that of patients diagnosed in the first 15 years of life. Contrary to younger and older age groups, 5-year survival and mortality reduction rates for AYA with cancer have remained stagnant, particularly for ethnic minority AYA. One explanation for this disparity is reduced participation in therapeutic or Phase III clinical trials as AYA with cancer are significantly less likely to enroll than children under 15 years of age. Lack of participation in clinical trials may reduce direct medical benefits and hinder advances in AYA cancer treatment. Because few empirical studies have addressed AYA participation in Phase III clinical trials, we conducted qualitative interviews with families of AYA with cancer and health care providers and discovered a more basic problem than low enrollment. That is, our results suggest that AYA are not involved in decision-making about clinical trial enrollment. AYA describe the presentation of treatment information as ineffective in promoting their understanding of treatment options, and providers feel challenged to maintain the engagement of AYA in treatment planning at diagnosis. Thus, research on how to increase involvement of AYA in clinical trial decision-making may be critical to addressing disparities in AYA cancer outcomes.

Using mixed methods and a randomized trial, the proposed study aims to develop and test preliminary efficacy of a web-based decision support intervention (DECIDES = AYA Deciding about Enrolling on a Clinical Intervention Trial: Decision Aid for Education and Support) to increase AYA involvement in clinical trial decision-making and improve decision-making processes for AYA and primary caregivers. DECIDES will be informed by: (1) Health Beliefs Model6 and Theory of Reasoned Behavior; (2) our qualitative study of AYA decision-making; (3) stakeholder input; and (4) established decision aid development guidelines. DECIDES will be developmentally appropriate, consider demand literacy, and contain components that increase knowledge about cancer and clinical trials, address attitudes to Phase III clinical trials, and weigh clinical trial benefits and barriers relative to values for AYA and their primary caregivers. In an iterative process, DECIDES will be revised based on feedback from our AYA Patient Steering Committee, their primary caregivers, and a Scientific Advisory Committee. Using mixed methods, acceptability and feasibility of DECIDES will be evaluated. Efficacy will be estimated for involvement and decision-making processes by comparing AYA (ages 15 to 24), who are newly diagnosed with leukemia, non-Hodgkin’s lymphoma or a sarcoma and offered treatment via a Phase III clinical trial, and their primary caregiver randomized to receive DECIDES (n = 24) or to usual care (n = 24). This research is central to the goals established by the Children’s Oncology Group and National Cancer Institute to address the unique and unmet needs of AYA with cancer through increased research on availability of and enrollment on clinical trials. Data from this study will inform a larger multi-site randomized trial to establish the efficacy of DECIDES.

Cross-Cultural Psychosocial Assessment Tool

Identifying factors associated with ongoing distress for children with cancer and their families is recommended to facilitate cancer care and assure timely provision of evidence based psychosocial care. There are commonalities among psychosocial risk factors and health disparities (e.g. resource limitations, socioeconomic status, social support, family problems, and cancer-related beliefs). Identifying these factors early in treatment in a psychometrically rigorous manner can contribute to the reduction of health disparities by connecting families to needed psychosocial resources and interventions. Brief, theoretically grounded user-friendly screening measures validated for families from diverse backgrounds (e.g. Spanish-speaking) are not currently available. We will address potential disparities by establishing a measure developed in our laboratory - the Psychosocial Assessment Tool (PAT) - as a valid screener of psychosocial risk for English and Spanish speaking families over the course of pediatric cancer treatment. The PAT is based on a conceptual model of risk and its implications for care in pediatric cancer – the Pediatric Preventative Psychosocial Risk Model. It includes brief screening of child (and sibling) and family factors/domains known to be associated with ongoing or escalating distress (e.g., resource considerations, socioeconomic status, child and sibling developmental and behavioral problems, and family problems, cancer-related beliefs).

This is a three-site prospective study of parents of children with cancer with the purpose of validating English and Spanish versions of a screener of psychosocial risk (the PAT) to be completed at multiple time points from diagnosis through the end of treatment. Mothers/fathers/caregivers of 540 (including123 Spanish speaking) children newly diagnosed with cancer at The Children's Hospital of Philadelphia, M.D. Anderson Cancer Center, and Nemours / Alfred I. duPont Hospital for Children will complete the PAT and validating measures of factors/domains in English or Spanish. Parents (caregivers) of children newly diagnosed with cancer will provide data using REDCap (with the option of paper and pencil if they prefer) at up to three data points (depending on their child’s treatment protocol): T1- Newly diagnosed (within one month of diagnosis); T2 - 6 months after diagnosis (for 70% of the sample, children will be on treatment; for 30% this will serve as the off-treatment data point), and T3 - off treatment (for children whose treatments is > 6 months in duration). Healthcare professionals who use the PAT (n = 15) from multiple sites in the U.S. and internationally will participate in interviews which will be analyzed qualitatively. At the conclusion of this study a validated screener of psychosocial risk for families, in English and Spanish, will be ready for use and broader dissemination in pediatric cancer. Identifying psychosocial risk factors will contribute to optimal provision of cancer care to all families by facilitating the delivery of evidence-based interventions specific to family needs. The assessment of factors related to health disparities on the PAT will provide for a brief measure of psychosocial risk that can be integrated into future research to assure the ongoing reduction of health disparities in cancer.

Mothers as Caregivers for Survivors of Brain Tumors

Survivors of childhood brain tumors are at high risk for tumor and treatment-related chronic morbidities including chronic health conditions and neurocognitive late effects. These sequelae result in decreased survivor health-related quality of life (HRQL) and decreased ability to achieve young adult (YA) developmental milestones such as living independently and being employed full time. Mothers often serve as long term caregivers and assist with self care; activities of daily living; and academic, vocational, and social endeavors. Caregivers’ perception of competence for managing these demands is an important yet understudied factor that potentially contributes to caregiver, survivor, and family outcomes. The Family Management Styles Framework (FMSF) offers an innovative perspective and considers caregiver competence as a component of family management (FM). While caregiving research has focused on perceived demands and psychosocial wellbeing of caregivers, our recent research tested a comprehensive model that extended understanding of caregiving to include perceived competence. Caregiver competence and survivor HRQL were enhanced when families functioned better. In related research with caregivers of children with chronic illness, caregiver competence significantly correlated with family functioning, child functional status, and child behavior. In addition, four meaningful patterns of FM were identified which contextualized the pivotal role of caregiver competence within FM patterns based on the focus, family focused (usual family routines and activities) versus condition focused (condition management). Better family and child functioning were significantly correlated with family focused patterns of FM in children with chronic illnesses. The gap in the science now is determining the patterns and correlates of FM for caregivers of young adult (YA) survivors of childhood brain tumors, including the role of caregiver competence to inform targeted, efficacious interventions for caregivers whose survivors have the poorest outcomes and depend on their families into adulthood. Recent meta-analyses of caregiver interventions concluded that intervention targets should be reconsidered to include the needs of caregivers (family focused) not exclusively condition management (condition focused) be multi-component and combine both cognitive components (e.g. problem-solving skills training) and skill building. We will use a test, translate, and evaluate participatory model with families to confirm appropriate targets for the intervention and to ensure the intervention is translatable into family life and clinical practice. Because caregivers are isolated and are heavy technology users in their search for information and support, web-based interventions will be included to increase accessibility.

Sleep in Pediatric Cancer

This American Cancer Society funded postdoctoral fellowship study, awarded to Dr. Daniel with Dr. Barakat and Dr. Schwartz’s mentorship, seeks to begin measure development for the first pediatric oncology sleep measure. The study will use mixed methods data collection to inform a theoretical model of sleep disturbances in children on treatment for cancer(Sleep Disturbance in Pediatric Cancer model), which will guide the creation of an item pool using NIH PROMIS methodology for the Pediatric Cancer Sleep Inventory (PCSI). Participants are caregivers of children ages 3-12 with Acute Lymphoblastic Leukemia. Sleep disturbances are common in pediatric cancer; fortunately, sleep is highly amenable to behavioral intervention. Findings from this study are relevant to understand and improve health-related quality of life and other health outcomes in children with cancer.


A large body of research confirms the psychological distress and the resiliencies of families as they initiate and complete treatment. W hile most families adapt and are able to cope with the stressors associated with treatment, there are currently many “missed opportunities” for identifying problems for which we have effective early or preventative behavioral treatments. If untreated, psychosocial stress has the potential to escalate and impact cancer care and outcomes more generally. For example, psychological factors are important, across cancers, in adherence to treatment and ongoing medical monitoring and health promoting behaviors. Although evidence based assessment and intervention approaches relevant across the course of treatment have been developed, they have yet to be translated into clinical care on a systematic basis. Indeed, the integration of patient report (family report) measures which can be used in clinical trials and for clinical decision-making is an important emerging research priority. This grant provides infrastructure support for the Section of Behavioral Oncology to conduct translational research directly relevant to clinical care. More specifically, it will support the development of a standardized psychosocial protocol and the means to generate important research data, that can be integrated into other clinical databases, by conducting assessment of all families in the Division of Oncology at diagnosis, during the course of treatment, and at the conclusion of treatment. Evidence based assessment is the first step in delivering evidence-based interventions. In the first aim we will assemble a developmentally-sensitive standardized psychosocial assessment protocol to assess psychosocial risks and resiliencies and pilot test its implementation at key points across the treatment trajectory. Aim 1 will demonstrate the feasibility of implementing an evidence-based research assessment protocol across cancer treatment that attends to the needs of children and families. W e will use a multi-informant methodology, including data from parents (mothers-fathers), patients and siblings (age 8+). The second aim is to utilize technology (e.g. web-based, tablet-based) to facilitate screening of patients and families and provide data which can be readily integrated into clinical care, other CCCR programs and data systems. In order to advance the integration of behavioral research data into clinical oncology research more broadly, psychosocial data must be collected in an expedient manner that will facilitate linkages with other relevant clinical and research databases. Completion of Aim 2 will establish the feasibility of using web and tablet-based technology for completing the assessment protocol. These steps will be invaluable in preparing subsequent grants, both in advancing the psychometric properties of the measures and in demonstrating our ability to aggregate and utilize datasets to answer clinically meaningful questions.

Thyroid Cancer Pilot Study

This study consists of a retrospective EPIC chart review of all patients newly diagnosed with differentiated thyroid cancer (DTC) in the Pediatric Thyroid Cancer Center. Information from standard clinic screening on health-related quality of life, distress, and medical and demographic variables will be generated through review of the EPIC chart. No identifiers will be collected. A Chart Review Form will guide collection of data from the EPIC chart. Item scores will be calculated from standard clinical intake measures completed by patients and their parents, which are located in the Media portion of the patients’ charts. The co-investigators, both experts in pediatric thyroid cancer, will use a standard scale (revised for thyroid cancer) to rate treatment intensity based on the chart review. The records of patients ages 6 and older, who were provided with standard screening at diagnosis of thyroid cancer and at 6 months post-diagnosis, will be reviewed. Screening is completed via parent- and patient report on measures of posttraumatic stress (self), posttraumatic growth (self), distress (self), and health-related quality of life and behaviors (parent proxy and patient self-report).

Family-based Transition Program for School-age Children with Sickle Cell Disease (RCT)

This NIH/NHLBI funded U54 aims to advance the goal of developing an effective, brief, family-based intervention, targeting quality of life and school functioning for youth with sickle cell disease, which may be provided within Comprehensive Sickle Cell Centers as part of their standard patient services program. Families of 6 -12-year-old children with sickle cell disease, who are in elementary school, will be randomized to the Family-based Transition Program for School-age Children intervention or a delayed intervention control group. The intervention will provide education and problem-solving training for disease management and school functioning. In 4 sessions offered over the course of a one-day intervention, 4 to 6 families (patient, caregivers, and school-age siblings) work together and individually to learn and apply the problem-solving skills training model to relevant examples and family-specific problems, culminating in an outline of family goals to target after the intervention. The three booster phone calls provide support to families in implementing the problem-solving model by addressing and refining goals and trouble-shooting barriers to implementation. Primary outcomes are quality of life and school functioning (school attendance, access to school resources), which are assessed at baseline, post-intervention (6 months post-baseline), and follow-up (12 months post-baseline) via home visit.

Acceptability and Feasibility of In Utero Hematopoietic Cell Transplantation (IUHCT) for Sickle Cell Disease (SCD) and Thalassemia Major

Sickle cell disease (SCD) and thalassemia major are autosomal recessive genetic blood disorders, medically referred to as hemoglobinopathies. SCD affects 1 in 500 African American newborns in the United States and according to the National Heart, Lung and Blood Institute, between 70,000 and 100,000 African Americans are currently living with the disease, with an average life expectancy of 40 to 50 years. Thalassemia major is common among people of Mediterranean and Asian descent and an estimated 1,000 people in the United States are currently living with the most severe form of thalassemia major. In utero hematopoietic cell transplantation (IUHCT) is a potentially curative treatment for both SCD and thalassemia major, yet questions of efficacy still exist and clinical data is needed to support progress in testing the treatment. Prenatal genetic testing and counseling (PGT&C) are essential for determining eligibility for an IUHTC trial, but its acceptability and awareness is low in ethnic minority communities. Likewise, engagement in clinical trials is also limited due to other significant barriers such as mistrust of use of genetic test information and a focus on risks over benefits of participation in clinical trials research. With sufficient recruitment and retention, clinical trials can be untaken in a manner that allows researchers to answer questions of efficacy of experimental treatments for SCD and thalassemia major. The aims of the proposed research are to establish the acceptability of PGT&C and feasibility of early Interventions for SCD and thalassemia major using a two-phase approach. In the first phase, we will survey young adults with SCD or thalassemia major and parents of a child with SCD or thalassemia major to determine knowledge of SCD or thalassemia major genetics and PGT&C and attitudes towards PGT&C, early interventions, and clinical trials research. In addition, we will explore the association of parenting stress or perceived general stress and health-related quality of life in shaping attitudes. The second phase, guided by results from the first phase, theory on health behavior change and decision support tool development guidelines, we will develop and test a decision aid that targets knowledge, attitudes and provides unbiased information about SCD, thalassemia major, PGT&C, and benefits and barriers to participation in the planned IUHCT clinical trial.