Building Evidence for Effective Palliative/End of Life Care for Teens With Cancer
Condition: Cancer
MeSH terms: Death
Study type: Interventional

Summary: 
      To test the efficacy of FACE-TC on key outcomes, the investigators propose using an
      intent-to-treat, longitudinal, prospective, multi-site, randomized controlled trial (RCT)
      design. Adolescents with cancer, aged 14 up to 20 years, and their families (N=130 dyads;
      N=260 participants) will be recruited and randomized to FACE-TC or Treatment as Usual (TAU)
      control. Participants will complete standardized questionnaires at baseline and 3, 6, 12, and
      18 months post-intervention. Our goal is to assess the extent to which FACE-TC helps
      adolescents and young adults with cancer and their families: (1) reach and maintain better
      congruence in treatment preferences over time; (2) improve their quality of life; and (3)
      document goals of care and advance directives earlier in the course of their potentially life
      limiting illness.
    

Detailed description: 
      The investigators propose a prospective, longitudinal, 2-arm RCT to test the efficacy of
      FACE-TC on key measurable outcomes through 18 months post-intervention. Dyads composed of
      adolescents with cancer and their families (N=130 dyads; 260 subjects) will be enrolled and
      randomized to either the FACE-TC intervention or Treatment as Usual (TAU) Control group at a
      ratio of 2:1 [N=87 FACE-TC dyads and N=43 TAU Control dyads]. The investigators estimate 30%
      attrition by the 18 month post-intervention assessment (20%-25% due to death/complications
      and 10% due to dropout). Of the original sample of 130 randomized dyads (N=260 subjects), the
      investigators estimate the investigators will have full longitudinal data at 18 months
      post-intervention for 91 dyads (N=182 subjects). Participants will be recruited from Akron
      Children's Hospital, St. Jude Children's Research Hospital and University of Minnesota
      Masonic Children's Hospital pediatric oncology programs. Participants will undergo written
      informed consent/assent. Eligible participants will be enrolled and complete the baseline
      assessment followed by randomization. Randomization will be at the level of the dyad.
      Allocation will be concealed from the RA-Assessor to prevent bias. Block randomization by
      study site will control for site differences. Intervention and Control Conditions: The
      curriculum based FACE-TC consists of: The Session 1 ACP Survey; Session 2 Respecting Choices
      Interview; and the Session 3 Five Wishes advance directive. To minimize the burden to ill
      adolescents, the investigators have chosen a Treatment as Usual comparison condition. This
      group will be provided with an advance care planning booklet/information only. Assessments
      occur at baseline, and 3, 6, 12, and 18 months post-intervention. At each site the
      assessments and intervention will be administered by a research team comprised of the site
      Co-Investigator and two Research Assistants (RA) (RA-Assessor & RA-Interventionist).Visit
      protocol: Screening Visit: The RA-Assessor presents the adolescent with cancer and family
      with an Information Sheet describing the study and conduct an initial assessment about
      whether they are eligible for enrollment. After consent/assent, further screening for
      inclusion/exclusion criteria is conducted. Baseline Visit: At enrollment and prior to
      randomization, baseline measures will be obtained. Entry of baseline data by the RA-Assessor
      will trigger computerized randomization of patient/family dyads to either FACE-TC
      intervention or TAU Control using a randomly permuted block design and a 2:1 ratio by study
      site. The Children's National clinical coordinator will then notify the RA-Interventionist
      who will schedule the next study visit. The adolescent and family will learn their assignment
      when the RA-Interventionist calls to schedule study sessions. Attendance will be recorded to
      assess effects of full vs. partial participation in FACE-TC. Follow-up Visits: RA-Assessor
      will obtain follow-up measures from the adolescent and family at 3, 6, 12 and 18 month post
      intervention.

      Site Co-Is will oversee site activities and provide weekly, face-to-face supervision of the
      RAs. They are responsible for recruitment, retention, safety, fidelity to protocol, and
      supervision and support of RAs. The RAs will assist with recruitment, screening, enrollment
      and baseline screening measure collection, as well as the day-to-day functioning. RAs will be
      blind to random assignment. RA-Interventionists will be trained to implement the protocol.
      Only the RA-Assessor will be permitted to administer post-randomization assessments.
      Children's National will serve as the data coordinating center and will be responsible for
      database design and maintenance and the statistical analyses. Sites will be overseen by a
      Safety Monitoring Committee (SMC). A 2-day Investigator Meeting will be held in Washington,
      District of Columbia (DC) and will include all site Co-Is, RA-Assessors and consultants. The
      protocol, its scientific rationale, underlying ethics issues, implementation including
      recruitment and retention, will be reviewed with the entire team. In month 9 of Year 1 there
      will be a 3-day training meeting of the RA-Interventionists and RA-Assessors on the
      intervention, which site-Co-Is will also attend. RA-Assessors will attend only one day of
      this training in order to maintain blindness. Site Initiation. To begin screening/enrollment
      (1) the protocol must be approved at each site's Institutional Review Board (IRB) and all
      personnel must be certified in Human Subjects Research training, (2) personnel are recruited
      and trained for RA roles, and (3) each RA-Interventionist must complete certification as a
      Next Steps-ACP Facilitator. Dr. Lyon and the Research Coordinator will verify that the site
      has all components in place for the logistics of screening, enrolling, scheduling, performing
      assessments, administering interventions, and collecting the data. To assure continuous
      quality for the intervention and its evaluation, monitoring will be ongoing. Dr. Lyon and Ms.
      Briggs will review the first 5 DVD/audio recordings of intervention sessions from each site
      to ensure fidelity with the protocol. Thereafter, they will randomly review 1 DVD per week,
      rotating sites. Dr. Lyon and Ms. Briggs will use a competency checklist. Dr. Lyon and
      Research Coordinator will monitor ongoing site IRB approval documentation and assist sites in
      annual continuing reviews. The Research Coordinator will keep copies of all regulatory forms,
      including consent-stamped templates from each site and staff members' Human Subjects Research
      Training approval certificates. Dr. Lyon and the Research Coordinator will perform twice
      yearly site monitoring visits while the intervention is being implemented to assure
      standardization of procedures and resolve any problems that are identified. They will review
      and confirm that all consents have occurred properly at the sites and that the sites are
      maintaining all participant and regulatory data. The REDCap database from the FACE-TC pilot
      will be updated and expanded for this study, and the systems for data entry will be revised
      to address multi-site implementation. A data dictionary will be created. An external Safety
      Monitoring Committee (SMC) will be assembled by Dr. Lyon with the responsibility of reviewing
      safety information, study progress, and other relevant data. The SMC will meet a minimum of
      once a year. Prior to parametric testing, scale reliabilities for multi-item measures (e.g.,
      pain/fatigue, child and parent psychological, spiritual/religious measures) will be assessed
      using Cronbach's alpha and their composite scores will be used for data analyses. Analytical
      Plan for AIM 1. To evaluate the efficacy of FACE-TC on adolescent-family congruence in
      treatment preferences. Congruence in decision-making for medical treatment will be tested
      based on agreement (i.e., both patient and his/her family choose the same option) on the
      Statement of Treatment Preferences in four different cancer-related situations. Kappa
      coefficients will be applied to assess chance-adjusted agreement between patient and family
      responses. Change in Kappa coefficient (congruence improvement) from baseline to each
      follow-up time point during the study period will be tested using bootstrapping technique.
      The latent growth model (LGM) with categorical outcome will be used to test Hypotheses H1a,
      i.e., FACE-TC participants will have a higher congruence rate over time. In the LGM, the
      investigators will set time scores, except those for identification purpose, as free
      parameters to let the shape of growth trajectory be determined by data. As such, the
      congruence development trajectory would have an empirically based nonlinear shape, instead of
      assuming a linear or nonlinear polynomial function. The investigators will apply the growth
      mixture model (GMM) to test heterogeneity of congruence development trajectories and identify
      possible patterns of congruence in development trajectories in the full sample. The latent
      class variable estimated from the GMM captures the pattern of congruence development
      trajectories. Time-invariant covariates will be used to predict the memberships of the latent
      trajectory groups; and time-varying covariates will be included to predict the level of
      congruence at different time points. To test Hypotheses H1b, the investigators will regress
      the latent growth slope factor and the latent class variable on FACE-TC intervention,
      controlling for covariates in the GMM to assess 1) how FACE-TC would affect the membership of
      the latent classes of congruence development; and 2) how the effect of FACE-TC on congruence
      change over time varies across the latent trajectory classes. Analytical Plan for AIM 2. To
      evaluate efficacy of FACE-TC on AYA quality of life and family QOL. The LGM and GMM models
      proposed for evaluating Aim 1 can be readily applied to evaluate Aim 2 and test Hypotheses H2
      where the outcome measures are continuous variables. When examining the effects of FACE-TC on
      QOL for AYAs with cancer and their families, socio-demographics will be controlled as
      time-invariant covariates, while time-varying covariates will be included in the model to
      predict measures of QOL at different time points. In addition, family caregiver
      appraisal/depression measured at the end of the study period will be included as a distal
      outcome in the GMM models, and how this distal outcome is associated with the patterns of the
      developmental trajectories of AYA QOL will be assessed. As the same model will be used to
      evaluate multiple outcomes, Bonferroni correction will be applied to exert a stringent
      control over false discovery. As attrition is inevitable in longitudinal studies, robust
      model estimator (e.g., MLR) using the full information maximum likelihood will be used for
      model estimation. Importantly, missing at random (MAR), instead of missing completely at
      random, can be assumed in MLR. MAR is a plausible assumption that allows missingness to be
      dependent on observed measures like intervention assignment. Analytical Plan for AIM 3. To
      evaluate the efficacy of FACE-TC on early completion of pACP goals of care and advance
      directives. First, the investigators will use the two-proportion z-test to test the
      differences in proportions of completion of pACP goals of care and advance directives between
      FACE-TC and control groups. Then logistic regressions will be used to test the Hypothesis H3,
      controlling for socio-demographics. Interaction between intervention and ethnicity will be
      included in the models to test ethnic disparity in regard to intervention efficacy. The
      investigators will also explore if FACE-TC improves the match between patients' goals of care
      and the medical care received at the EOL among the adolescents who may die. Descriptive
      statistics will be used to estimate the frequencies of the study variables. Chi-square
      statistics with Fisher Exact tests will be used to assess the difference in the match between
      FACE-TC and controls; and exact logistic regression will be applied to examine the effect of
      FACE-TC on such a match, controlling for covariates. For continuous outcomes with a modest
      observation autocorrelation (p=0.20) and moderate effect size (delta=0.35), the estimated
      sample size to achieve a power of 0.80 at =0.05 level and detect a moderate effect size
      (delta=0.35) is about N=76 individuals at each of the 5 observation time points. For binary
      outcomes, a sample size of N=70 can achieve a power of 0.80 to detect a moderate response
      probability difference of d=0.17 given p=0.20. Our proposed sample of N=130 dyads will ensure
      a large enough statistical power for our proposed longitudinal analyses on patient data and
      parent data, respectively. For the cross-sectional logistic regression model proposed to
      evaluate Aim 3, a sample size of N=100 would achieve a power of 0.83 at alpha=0.05 level to
      detect an odds ratio of 4.
    

Intervention name(s): FAmily CEntered Advance Care Planning for Teens with Cancer
Intervention type(s): Behavioral
Intervention description(s): 3 session weekly intervention: 1) survey completed by adolescent and family (surrogate decision maker) separately with facilitator; 2) Respecting Choices structured interview about patient's representation of illness, goals of care, hopes, treatment preferences; 3) completion of an advance directive.
Other intervention name(s): FACE-TC
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: pediatric advance care planning; adolescent; family; palliative care; end of life; communication; decision making; surrogate decision maker; health care proxy; intervention; randomized clinical trial; cancer; quality of life; spiritual; religion; treatment congruence; treatment preferences; FAmily CEntered (FACE) Advance Care Planning