Building Evidence for Effective Palliative/End of Life Care for Teens With Cancer

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. Study sites will maintain documentation of participants' consent.
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.

AYA Inclusion Criteria:

- Ever diagnosed with cancer;

- Knows his or her cancer status;

- Ages of 14 up to 20 years;

- Ability to speak English;

- Consent from the legal guardian for adolescents aged 14-17;

- Consent from a surrogate for adolescents aged 18-20;

- Assent from adolescent aged 14-17;

- Consent from adolescent aged 18-20;

Inclusion Criteria for Legal Guardians of Adolescents Age 14-17:

- Legal guardian of assenting adolescent participant;

- Knows cancer status of adolescent;

- Adolescent willingness to discuss problems related to cancer with them;

- Age 18 or older;

- Ability to speak English;

- Consent to participate; Consent for his/her adolescent to participate;

Inclusion Criteria for Surrogates of AYAs Age 18-20:

- Selected by adolescent aged 18 to 20;

- Knows cancer status of adolescent;

- Age 18 or older;

- Ability to speak English;

- Willingness to discuss problems related to cancer and EOL;

- Consent to participate;

Exclusion Criteria - for AYA or surrogate decision-maker:

Developmental delay; foster care; active homicidality or suicidality, depression in the
severe range