Advanced Cancer
Conditions
Keywords
Advanced Cancer
Brief summary
PediQUEST Response proposes a new system of care that expects to improve quality of life in children, adolescents, and young adults with advanced cancer and their parents. The investigators want to learn whether patients that are cared for using PediQUEST Response do in fact feel better than those receiving usual care. National recommendations call for early palliative care (PC) integration for seriously ill children to ease suffering, however, very few randomized controlled trials (RCTs) have evaluated whether PC improves child and family outcomes. In prior work, the investigators developed the Pediatric Quality of Life and Evaluation of Symptoms Technology (PediQUEST/PQ), a software that collects electronic Patient-Reported Outcomes (e-PROMS) and generates feedback reports. Now, the PI and research team developed PediQUEST Response (Response to Pediatric Oncology Symptom Experience). PediQUEST Response includes an enhanced PediQUEST system (web-based and with an App that allows to answer surveys and see reports), that is coupled with early integration of a palliative care consulting team (Response team). This dual strategy will help to standardize the family report of distress, which will be done through the PediQUEST system. It will also help standardize the providers' response to such distress, as providers will be specifically trained. Pilot work for PediQUEST Response found it feasible, well received by families and oncologists, and potentially effective. Thus, the overall goal of this study is to conduct a RCT of PQ Response versus usual care at four large pediatric oncology centers among 136 children ≥2 years old with advanced cancer. Hypotheses include a) children receiving the intervention will have better (higher) quality of life scores b) parents of children in the intervention group will report better state-anxiety, depression and symptom-related stress scores, and c) intervention group families will demonstrate higher levels of activation.
Detailed description
Background: Integration of palliative care (PC) has been associated with better health related quality of life (HRQoL) and longer survival in adults and their caregivers. Yet, only a few randomized controlled trials (RCTs) have evaluated whether PC integration improves child and family outcomes. The investigators propose to evaluate the effects of an early PC intervention (PediQUEST Response) for pediatric oncology patients (from here on called patients) with advanced cancer on patient and parent outcomes. Aims: * Aim 1 To evaluate whether PediQUEST Response, compared to usual care, improves patient's HRQoL (primary outcome) and symptom burden. * Aim 2 To evaluate the impact of the intervention on parent psychological distress and symptom-related stress outcomes. * Aim 3 To compare family activation by measuring coping strategies between study entry and 16 weeks, use of non-pharmacologic strategies for symptom treatment, and No. of documented psychosocial clinician encounters between intervention and control arms. Design: Multisite, randomized (1:1), controlled, un-blinded, effectiveness trial comparing PediQUEST Response (intervention) vs usual cancer care (comparator). Setting: Dana-Farber/Boston Children's Cancer and Blood Disorders Center (DFBCC), Seattle Children's Hospital, Children's Hospital of Philadelphia Cancer Center, and St. Jude's Research Hospital. Participants: The target sample size (SS) is 136 patient-parent dyads (N=68/arm, 34/site) ≥2 years old receiving cancer care at the participating sites and with advanced cancer who have not been referred to the palliative care team. To achieve this SS, 200 dyads will be recruited. Interventions: * PediQUEST Response: consists of combining a patient-mediated activation intervention (weekly feedback of patient-reported outcomes to families and providers using the online PediQUEST web system or mobile App) with early integration of the PC team (consisting of an initial meeting with providers and family with subsequent follow-up including a monthly encounter or as needed number of encounters based on PediQUEST reports and other clinical indications). PC teams will receive standardized training before starting the intervention to learn how to interpret and react to PediQUEST reports and to encourage them to build a close relationship with the patient's primary oncology team. Response teams will also receive ongoing support throughout the intervention period through their local PIs and an expert listserv. * Usual Cancer Care (comparator): participants in this arm will receive usual cancer care provided at the sites, which can include PC consultation as deemed necessary by oncologist, and will use the PediQUEST web system to complete surveys but no reports will be generated. Methods: Following enrollment, patient (if older than 5 years) and parents of all enrolled patients will receive weekly PediQUEST-Surveys including a patient HRQoL measure (PedsQL) and a symptom burden scale (PediQUEST-MSAS). Parents will complete a Baseline Survey Packet (will collect socio-demographic information, trait-anxiety, social support, stress, and coping style). A two-week run-in period will identify and exclude non-responder dyads (i.e. \<2 answered PediQUEST-Surveys out of 3 assigned). Responders will be randomized to the intervention or control arms (concealed allocation) and followed up for 16-weeks (16-w). Those assigned to the intervention will begin receiving PediQUEST Response (feedback reports + response team intervention). Parents in both arms will be assigned monthly questionnaires (measuring parental distress, HRQoL, and use of complementary therapies; on weeks 8 and 16 symptom-related stress and coping will also be measured). All surveys will be administered through PediQUEST web. Process measures will be collected throughout the study, and semi-structured exit interviews conducted in participating patients, parents, and a sub-sample of providers. Participants in the intervention arm will be offered continued care by the PC team once the intervention ceases. Outcomes: Average difference between the two treatment arms in: (i) Patient outcomes: primary study outcome is the mean child's quality of life total score as reported by parent and patient over 16 weeks; we will also look at quality of life subscale scores, mean patient symptom burden scores, parent distress (anxiety, depression and symptom related stress), and family activation (coping, and "symptom treatment activation"). See details below in outcomes section.
Interventions
OTHERPediQUEST Response
PediQUEST Response consists of regular feedback of electronic patient reported outcomes (child symptoms and quality of life) to providers and families coupled with involvement of the palliative care team, who will meet with families and providers within three weeks of randomization and follow-up at least monthly as deemed necessary based on PediQUEST feedback reports and other clinical indications.
OTHERUsual Cancer Care
Patients assigned to the usual cancer care arm, will receive the standard care provided by participating sites + be required to complete PediQUEST surveys (but no reports will be generated).
Sponsors
Joanne Wolfe, MD, MPH
Children's Hospital of Philadelphia
Children's Hospitals and Clinics of Minnesota
University of Alabama at Birmingham
Deakin University
Boston Children's Hospital
Ann & Robert H Lurie Children's Hospital of Chicago
Baylor College of Medicine
Dana-Farber Cancer Institute
National Institute of Nursing Research (NINR)
St. Jude Children's Research Hospital
Nationwide Children's Hospital
Seattle Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pediatric oncology patients (children, adolescents, or young adults), and one of their parents, receiving routine cancer care at one of the participating centers -and not in remission and off cancer-directed treatment-that have: * (i) advanced cancer defined as: at least a 2-week history of progressive, recurrent, or non-responsive cancer of any type, or any brainstem tumor, or a grade IV Glioblastoma Multiforme, or decision not to pursue cancer-directed therapy in place, or or any other progressive/recurrent solid or brain tumor, and are * (ii) palliative care naive, defined as the palliative care team not currently integrated into their regular cancer care.
Exclusion criteria
The patient-parent dyad would be excluded if * patients are older than 18 years of age and no parent is involved in his/her care, or * if patient is under the care of foster parents who do not have legal guardianship, or * if both parents do not speak English or Spanish, or are unable to understand and complete surveys, or * if the patient has a non-brainstem low-grade glioma with localized progression/relapse only, or * is expected to receive a stem cell transplant within the next 18 weeks, or * life expectancy is less than two months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Child Quality of Life | Baseline and 16 weeks (measured monthly from point of randomization, the 16-week average was used). | The primary outcome was child Pediatric Quality of Life Inventory 4.0 (PedsQL) total score, analyzed by respondent: (a) parent-reported for all enrolled children (n=154), and (b) child-reported (if 5 years of age or older) (n=103). PedsQL total scores are calculated as the average of the 23 items that integrate the tool. Scores range from 0-100 (100 is excellent quality of life). A score of \<70 is considered fair/poor quality of life. Intervention effect was measured as the mean difference between arms of the difference between the 16-week average and baseline scores estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Child Quality of Life - Physical Subscale | Baseline (average of run-in scores, i.e. 2-3 scores) and 16 weeks (measured weekly from point of randomization, the 16-week average was used). | Secondary child PedsQL subscale outcomes included: (a) PedsQL physical (8 items) and (b) psychosocial (15 items) subscale scores (range 0-100, higher is better). Intervention effect was measured as the mean difference between arms of the difference between the 16-week average and baseline scores estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Child Quality of Life - Psychosocial Subscale | Baseline (average of run-in scores, i.e. 2-3 scores) and 16 weeks (measured weekly from point of randomization, the 16-week average was used). | Secondary child PedsQL subscale outcomes included: (a) PedsQL physical (8 items) and (b) psychosocial (15 items) subscale scores (range 0-100, higher is better). Intervention effect was measured as the mean difference between arms of the difference between the 16-week average and baseline scores estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Child Symptom Burden-PQMSAS Total | Baseline (average of run-in scores, i.e. 2-3 scores) and 16 weeks (measured weekly from point of randomization, the 16-week average was used). | Secondary child outcome PediQUEST-Memorial Symptom Assessment Scale (PQ-MSAS) total scores calculated as the average of individual symptom scores (26 for teens and caregivers and 8 for children aged 7-12). Individual symptom scores are calculated as the average of the three symptom subquestions. All symptom scores and total scores range from 0-100, 100 indicates higher symptom burden. Intervention effect calculated as: mean difference between arms of the difference between the 16-week average and baseline scores as reported by (a) the parent for all enrolled children and (b) the patient, if 7 years of age or older. Effect estimated using mixed linear models with child as a random effect. Unadjusted models included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Child Symptom Burden- PQMSAS-physical Subscale | 16 weeks (measured weekly from point of randomization) | Secondary child outcome PediQUEST-Memorial Symptom Assessment Scale (PQ-MSAS) physical subscale scores calculated as the average of eight physical symptom scores (only for teens and caregivers). Scores range from 0-100, 100 indicates higher symptom burden. Time Frame: Baseline (average of run-in scores, i.e. 2-3 scores) and 16 weeks (measured weekly from point of randomization, the 16-week average was used). Intervention effect was measured as the mean difference between arms of the difference between the 16-week average and baseline scores as reported by (a) the parent for all enrolled children and (b) the patient, if ≥13 years of age. Effect estimated using mixed linear models with child as a random effect. Unadjusted models included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Child Symptom Burden- PQMSAS-psychosocial Subscale | Baseline (average of run-in scores, i.e. 2-3 scores) and 16 weeks (measured weekly from point of randomization, the 16-week average was used). | Secondary child outcome PediQUEST-Memorial Symptom Assessment Scale (PQ-MSAS) psychosocial subscale scores calculated as the average of 6 psychological symptom scores (only for teens and caregivers). Scores range from 0-100, 100 indicates higher symptom burden. Intervention effect was measured as the mean difference between arms of the difference between the 16-week average and baseline scores as reported by (a) the parent for all enrolled children and (b) the patient, if ≥13 years of age. Effect estimated using mixed linear models with child as a random effect. Unadjusted models included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Parental Distress (Anxiety) | Baseline and 16 weeks (measured monthly from point of randomization, the 16-week average was used). | Parent anxiety measured using Spielberger's-State Anxiety Inventory-State tool (STAI-S). Scores range from 20 to 80, with higher scores correlating with greater anxiety. Intervention effect estimated as the mean difference between arms of the difference between the 16-week average and baseline scores estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Parental Distress (Depression) | Baseline and 16 weeks (measured monthly from point of randomization, the 16-week average was used). | Parent depression measured using the Center for Epidemiologic Studies Short Depression Scale (CES-D-10) tool. Scores range from 0 to 30 (Score of 10 or higher indicates the presence of significant depressive symptoms). Intervention effect estimated as the mean difference between arms of the difference between the 16-week average and baseline scores estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Family Activation (Symptom Treatment Activation - Number of Complementary Therapies (UCT) Used) | Baseline and 16 weeks (measured monthly from point of randomization, the 16-week average was used). | Number of complementary therapies used over the past month were reported by parents using an ad hoc checklist of 33 therapies based on an NIH Center for Complementary and Integrative Health list. Parents reported both use (yes/no) of each therapy and reasons for use. Intervention effect estimated as the mean difference between arms of the difference between the 16-week average and baseline number of complementary therapies used estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Parental Distress (Stress) | Baseline and 16 weeks (measured at weeks 8 and 16 from point of randomization, the 16-week average was used). | Parent stress was measured using an adapted version of the Response to Stress Questionnaire-Pain portion. The tool assesses 12 potential stress sources. Scores range from 1-4 (higher means more stress). Symptom-related stress score calculated as the sum of the 12 item scores. Intervention effect estimated as the mean difference between arms of the difference between the 16-week average and baseline scores estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Family Activation (Coping-instrumental Support) | Baseline and 16 weeks (measured at weeks 8 and 16 from point of randomization, the 16-week average was used). | Coping was measured using selected items from the short version of the Coping Orientation to Problems Experienced Inventory (BRIEF COPE) tool including the instrumental support scale score. Scale score is calculated as the average of the items that measure the strategy. Items scored 1-4 (higher means using that strategy a lot). Intervention effect estimated as the mean difference between arms of the difference between the 16-week average and baseline scores estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. We report below on instrumental support scores. |
| Change in Family Activation (Symptom Treatment Activation - UCT - Types) | Baseline and 16 weeks (measured monthly from point of randomization, the 16-week average was used). | Types of complementary therapies used were measured using an ad hoc checklist of complementary therapies as explained for outcome 9. Complementary measures were grouped as physical, psychological, nutritional, combined, and whole-system approaches based on NCCIH framework. Intervention effect estimated as the mean difference between arms of the difference between the 16-week average and baseline types of therapies used estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
| Change in Family Activation (Symptom Treatment Activation - Use of Psychosocial Services) | Data were collected from randomization point to 16 weeks point. | Information on use of psychosocial services was gathered from the medical record and operationalized as "number of encounters documented with psychosocial clinicians." Intervention effect estimated as the mean difference between arms of the 16-week average of encounters with psychosocial clinicians estimated using mixed linear models with child as a random effect. For unadjusted models we included study arm, time (categorical, 0 to 16 weeks) and arm-by-time interaction as fixed effects. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJoanne Wolfe, MD
Dana-Farber Cancer Institute
Participant flow
Recruitment details
Participants were recruited from five U.S. pediatric oncology centers between March 2018 and September 2022. Following enrollment, dyads completed a 2-week run-in period to identify responders. Responders were defined as dyads in which both parent and patient completed at least 2 of 3 assigned PediQUEST surveys during the run-in period. Eligible responder dyads were randomized 1:1 to the PediQUEST Response intervention or Usual Cancer Care and followed for 16 weeks.
Pre-assignment details
We enrolled 194 child-parent dyads (we stopped short of the protocol target 196 when reaching randomization target). Forty dyads did not meet randomization criteria (non-responders) and were excluded. We initially planned to randomize 136 dyads; after DSMB review of a planned interim analysis, the target increased to ≥150 dyads based on baseline scores distributions. Enrollment stopped after the randomization target was achieved. A total of 154 dyads (total: 308 participants) were randomized.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Child mean age (SD), y | 11.0 Years STANDARD_DEVIATION 6.1 |
| Age, Continuous Parent age (SD), y | 42.5 Years STANDARD_DEVIATION 8.6 |
| Age, Customized Child age group ≥13 yo | 30 Participants |
| Age, Customized Child age group 2-7 yo | 56 Participants |
| Age, Customized Child age group 8-12 yo | 40 Participants |
| Child Clinical status at study entry - Disease status ≥2nd Remission (all in active treatment) | 6 Participants |
| Child Clinical status at study entry - Disease status Progression | 51 Participants |
| Child Clinical status at study entry - Disease status Regression | 55 Participants |
| Child Clinical status at study entry - Disease status Relapse | 32 Participants |
| Child Clinical status at study entry - Treatment status Off treatment (completed) | 4 Participants |
| Child Clinical status at study entry - Treatment status On treatment | 68 Participants |
| Child Clinical status at study entry - Treatment status Treatment discontinued | 2 Participants |
| Child-reported baseline quality of life score, mean (SD) | 68.3 Scores on a scale STANDARD_DEVIATION 16.1 |
| Child Tumor type Brain tumor | 42 Participants |
| Child Tumor type Hematological malignancy | 24 Participants |
| Child Tumor type Solid tumor | 32 Participants |
| Ethnicity (NIH/OMB) Child ethnicity (gathered from medical records) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Child ethnicity (gathered from medical records) Not Hispanic or Latino | 128 Participants |
| Ethnicity (NIH/OMB) Child ethnicity (gathered from medical records) Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Parent ethnicity (self-reported) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Parent ethnicity (self-reported) Not Hispanic or Latino | 66 Participants |
| Ethnicity (NIH/OMB) Parent ethnicity (self-reported) Unknown or Not Reported | 0 Participants |
| Parent education level Associate degree or lower | 76 Participants |
| Parent education level Bachelor's degree or higher | 36 Participants |
| Parent education level Missing or Not reported | 1 Participants |
| Parent marital status Married/Partnered | 58 Participants |
| Parent marital status Not reported/Missing | 0 Participants |
| Parent marital status Single/Divorced/Separated/Widowed | 15 Participants |
| Parent-reported baseline quality of life scores, mean (SD) | 61.8 Scores on a scale STANDARD_DEVIATION 19 |
| Race/Ethnicity, Customized Child race, n (%) (gather from medical records) Asian | 9 Participants |
| Race/Ethnicity, Customized Child race, n (%) (gather from medical records) Black/African American | 5 Participants |
| Race/Ethnicity, Customized Child race, n (%) (gather from medical records) Missing | 0 Participants |
| Race/Ethnicity, Customized Child race, n (%) (gather from medical records) Other or Multiple | 5 Participants |
| Race/Ethnicity, Customized Child race, n (%) (gather from medical records) White | 59 Participants |
| Race/Ethnicity, Customized Parent race, n (%) (self-reported) Asian | 4 Participants |
| Race/Ethnicity, Customized Parent race, n (%) (self-reported) Black/African American | 9 Participants |
| Race/Ethnicity, Customized Parent race, n (%) (self-reported) Missing | 0 Participants |
| Race/Ethnicity, Customized Parent race, n (%) (self-reported) Other or Multiple | 11 Participants |
| Race/Ethnicity, Customized Parent race, n (%) (self-reported) White | 51 Participants |
| Sex/Gender, Customized Child Female gender, n (%) | 37 Participants |
| Sex/Gender, Customized Child Male gender, n (%) | 37 Participants |
| Sex/Gender, Customized Parent Female gender, n (%) | 129 Participants |
| Sex/Gender, Customized Parent Male gender, n (%) | 11 Participants |
| Site Site 1 | 24 Participants |
| Site Site 2 | 12 Participants |
| Site Site 3 | 28 Participants |
| Site Site 4 | 19 Participants |
| Site Site 5 | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 74 |
| other Total, other adverse events | 0 / 80 | 0 / 74 |
| serious Total, serious adverse events | 0 / 80 | 0 / 74 |
Outcome results
None listed