Building Evidence for Effective Palliative/End of Life Care for Teens With Cancer (FACE-TC)

St. Jude Children's Research Hospital, Akron Children's Hospital, National Institute of Nursing Research (NINR), Masonic Cancer Center, University of Minnesota

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.

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.

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

Adolescent/family dyads randomized to the experimental condition receive Family Centered Advance Care Planning for Teens with Cancer (FACE-TC) intervention - 3 sessions scheduled one week apart of approximately 60 minutes duration each. Session 1 - Lyon Advance Care Planning Survey-Adolescent & Surrogate versions. Session 2 - Respecting Choices Interview facilitated by trained/certified facilitator with adolescent and family. Focuses on patient's understanding of their illness, possible complications, goals of care and treatment preferences in 3 bad outcome situations; and the Session 3 - Five Wishes an advance directive.

Adolescent/family dyads randomized to the treatment as usual (TAU) condition receive written information on advance care planning, but no active intervention.

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.

Assess adolescent Physical Function Mobility; Physical Function Upper Extremity; Emotional distress-Anxiety; Emotional Distress-Depressive Symptoms; Fatigue; and Pain Interference. 8 items each.

Assess the construct of spiritual functioning and religious practices, e.g. religious preferences and practices, feeling God's presence. Nonreligious participants can pass on these items. 38 items.

Change from baseline in spiritual quality of life at 3, 6, 12 and 18 months post baseline compared to controls

Change from baseline in spiritual quality of life at 3, 6, 12 and 18 months post baseline compared to controls

Assess documentation of goals of care, advance directives and care received last week to last month of life.

Two weeks post-baseline for control; two weeks post-baseline for intervention--immediately following Session 2.

Two weeks post-baseline for control; two weeks post-baseline for intervention--immediately following Session 2.

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

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Lyon ME, Jacobs S, Briggs L, Cheng YI, Wang J. Family-centered advance care planning for teens with cancer. JAMA Pediatr. 2013 May;167(5):460-7. doi: 10.1001/jamapediatrics.2013.943.

Lyon ME, Garvie PA, Briggs L, He J, McCarter R, D'Angelo LJ. Development, feasibility, and acceptability of the Family/Adolescent-Centered (FACE) Advance Care Planning intervention for adolescents with HIV. J Palliat Med. 2009 Apr;12(4):363-72. doi: 10.1089/jpm.2008.0261.

Lyon ME, Garvie PA, Briggs L, He J, Malow R, D'Angelo LJ, McCarter R. Is it safe? Talking to teens with HIV/AIDS about death and dying: a 3-month evaluation of Family Centered Advance Care (FACE) planning - anxiety, depression, quality of life. HIV AIDS (Auckl). 2010;2:27-37. doi: 10.2147/hiv.s7507. Epub 2010 Feb 18.

Lyon ME, Garvie PA, McCarter R, Briggs L, He J, D'Angelo LJ. Who will speak for me? Improving end-of-life decision-making for adolescents with HIV and their families. Pediatrics. 2009 Feb;123(2):e199-206. doi: 10.1542/peds.2008-2379.

Jacobs S, Perez J, Cheng YI, Sill A, Wang J, Lyon ME. Adolescent end of life preferences and congruence with their parents' preferences: results of a survey of adolescents with cancer. Pediatr Blood Cancer. 2015 Apr;62(4):710-4. doi: 10.1002/pbc.25358. Epub 2014 Dec 24.

Wilkins ML, Dallas RH, Fanone KE, Lyon ME. Pediatric palliative care for youth with HIV/AIDS: systematic review of the literature. HIV AIDS (Auckl). 2013 Jul 29;5:165-79. doi: 10.2147/HIV.S44275. Print 2013.

Garvie PA, He J, Wang J, D'Angelo LJ, Lyon ME. An exploratory survey of end-of-life attitudes, beliefs, and experiences of adolescents with HIV/AIDS and their families. J Pain Symptom Manage. 2012 Sep;44(3):373-85.e29. doi: 10.1016/j.jpainsymman.2011.09.022. Epub 2012 Jul 7.

Lyon ME, McCabe MA, Patel KM, D'Angelo LJ. What do adolescents want? An exploratory study regarding end-of-life decision-making. J Adolesc Health. 2004 Dec;35(6):529.e1-6. doi: 10.1016/j.jadohealth.2004.02.009.

Rosenberg AR, Wolfe J, Wiener L, Lyon M, Feudtner C. Ethics, Emotions, and the Skills of Talking About Progressing Disease With Terminally Ill Adolescents: A Review. JAMA Pediatr. 2016 Dec 1;170(12):1216-1223. doi: 10.1001/jamapediatrics.2016.2142.

Lyon ME, D'Angelo LJ, Dallas RH, Hinds PS, Garvie PA, Wilkins ML, Garcia A, Briggs L, Flynn PM, Rana SR, Cheng YI, Wang J. A randomized clinical trial of adolescents with HIV/AIDS: pediatric advance care planning. AIDS Care. 2017 Oct;29(10):1287-1296. doi: 10.1080/09540121.2017.1308463. Epub 2017 Mar 30.

Weaver MS, Anderson B, Cole A, Lyon ME. Documentation of Advance Directives and Code Status in Electronic Medical Records to Honor Goals of Care. J Palliat Care. 2020 Oct;35(4):217-220. doi: 10.1177/0825859719860129. Epub 2019 Jul 7.

Feudtner C, Rosenberg AR, Boss RD, Wiener L, Lyon ME, Hinds PS, Bluebond-Langner M, Wolfe J. Challenges and Priorities for Pediatric Palliative Care Research in the U.S. and Similar Practice Settings: Report From a Pediatric Palliative Care Research Network Workshop. J Pain Symptom Manage. 2019 Nov;58(5):909-917.e3. doi: 10.1016/j.jpainsymman.2019.08.011. Epub 2019 Aug 21.

Watson A, Weaver M, Jacobs S, Lyon ME. Interdisciplinary Communication: Documentation of Advance Care Planning and End-of-Life Care in Adolescents and Young Adults With Cancer. J Hosp Palliat Nurs. 2019 Jun;21(3):215-222. doi: 10.1097/NJH.0000000000000512.

Needle J, Brunnquel D, Lyon M. Mature minors, mature decisions: Advance care planning for adolescent patients with life-limiting illness. Journal of Pediatric Ethics! Advanced Care Planning and End of Life. 2018;1(3).

Weaver MS, Bell CJ, Diver JL, Jacobs S, Lyon ME, Mooney-Doyle K, Newman AR, Slutsman J, Hinds PS. Surprised by Benefit in Pediatric Palliative Care Research. Cancer Nurs. 2018 Jan/Feb;41(1):86-87. doi: 10.1097/NCC.0000000000000576. No abstract available.

Needle JS, Peden-McAlpine C, Liaschenko J, Koschmann K, Sanders N, Smith A, Schellinger SE, Lyon ME. "Can you tell me why you made that choice?": A qualitative study of the influences on treatment decisions in advance care planning among adolescents and young adults undergoing bone marrow transplant. Palliat Med. 2020 Mar;34(3):281-290. doi: 10.1177/0269216319883977. Epub 2019 Oct 29.

Wiener L, Zadeh BS, Battles H, Sender L, Fasciano K, Heath C, Lyon ME, Donavan KA, Naronoha Ferrazde Arruda Colli M, Pao M. Courageous Conversations: Advance Care Planning and Family Communication. Pediatric Blood & Cancer, S596, October, 2018

Curtin KB, Watson AE, Wang J, Okonkwo OC, Lyon ME. Pediatric advance care planning (pACP) for teens with cancer and their families: Design of a dyadic, longitudinal RCCT. Contemp Clin Trials. 2017 Nov;62:121-129. doi: 10.1016/j.cct.2017.08.016. Epub 2017 Aug 24.

Gaines ThompkinsJ, Friebert S, Baker J, Needle J, Cheng Y, Lyon M. Effect of FAmily CEntered (FACE) advance care planning (ACP) on families' appraisals of caregiving for their teens with cancer. J Pain Symptom Manage 2019;57(2):446-447. PMID: 30267845

Friebert S, Gaines (Thompkins) J, Needle J, Baker J, Cheng Y, Lyon M. What do adolescents want? Values, goals and beliefs of teens with cancer. J Pain Symptom Manage 2019;57(2):378.

Grossoehme DH, Friebert S, Baker JN, Tweddle M, Needle J, Chrastek J, Thompkins J, Wang J, Cheng YI, Lyon ME. Association of Religious and Spiritual Factors With Patient-Reported Outcomes of Anxiety, Depressive Symptoms, Fatigue, and Pain Interference Among Adolescents and Young Adults With Cancer. JAMA Netw Open. 2020 Jun 1;3(6):e206696. doi: 10.1001/jamanetworkopen.2020.6696.

Friebert S, Grossoehme DH, Baker JN, Needle J, Thompkins JD, Cheng YI, Wang J, Lyon ME. Congruence Gaps Between Adolescents With Cancer and Their Families Regarding Values, Goals, and Beliefs About End-of-Life Care. JAMA Netw Open. 2020 May 1;3(5):e205424. doi: 10.1001/jamanetworkopen.2020.5424.

Thompkins J, Baker JN, Friebert S, Needle J, Wang J, Cheng YI, Lyon ME. Effect of FAmily CEnterd (FACE) advance care planning (ACP) on families' appraisals of caregiving for their teen with cancer. 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. (ASCO Virtual Scientific Program). J Clin Oncol 38: 2020 (suppl; abstr e22533) DOI:10.1200/JCO.2020.38.15_suppl.e2253

Schreiner KL, Grossoehme DH, Baker JN, Needle J, Friebert S, Lyon ME. Being healthy and living life as if I never had cancer": The meaning of "living well" from adolescents with cancer. J Clin Oncol 38: 2020 (suppl; abstr e22532) DOI: 10.1200/JCO.2020.38.15_suppl.e22532

Livingston J, Cheng Y, Wang J, Tweddle T, Friebert S, Baker J, Thompkins J, Greenberg I, Lyon M. FP029 SIOP19-1654 Shared Spiritual Beliefs Between Adolescents with Cancer and Their Families: An Exploration of Social Determinants of Spiritual Well-Being. Supplement: Abstracts from the 51st Congress of the International Society of Paediatric Oncology (SIOP) Lyon, France, October 23-26, 2019 Pediatric Blood & Cancer. December 2019;66: IssueS4 e27989 https://doi.org/10.1002/pbc.27989

Abstracts from the 51st Congress of the International Society of Paediatric Oncology (SIOP) Lyon, France, October 23-26, 2019. Pediatr Blood Cancer. 2019 Dec;66 Suppl 4:e27989. doi: 10.1002/pbc.27989. No abstract available.

Lyon ME, Grossoehme DH, Baker JN, Friebert S, Cheng Y, Chrastek J, Thompkins J, Tweddle M, Wang J, Needle J. Relationship of spiritual constructs to mental health PROs in adolescents with cancer.DOI: 10.1200/JCO.2019.37.31_suppl.136 Journal of Clinical Oncology 37, no. 31_suppl (November 01, 2019) 136-136. Published online November 25, 2019

Needle JS, Friebert S, Thompkins JD, Grossoehme DH, Baker JN, Jiang J, Wang J, Lyon ME. Effect of the Family-Centered Advance Care Planning for Teens with Cancer Intervention on Sustainability of Congruence About End-of-Life Treatment Preferences: A Randomized Clinical Trial. JAMA Netw Open. 2022 Jul 1;5(7):e2220696. doi: 10.1001/jamanetworkopen.2022.20696.

Baker JN, Friebert S, Needle J, Jiang J, Wang J, Lyon ME. An Intervention in Congruence for End-of-Life Treatment Preference: A Randomized Trial. Pediatrics. 2022 May 1;149(5):e2021054796. doi: 10.1542/peds.2021-054796.

Thompkins JD, Needle J, Baker JN, Briggs L, Cheng YI, Wang J, Friebert S, Lyon ME. Pediatric Advance Care Planning and Families' Positive Caregiving Appraisals: An RCT. Pediatrics. 2021 Jun;147(6):e2020029330. doi: 10.1542/peds.2020-029330. Epub 2021 May 6.

- Baker JN (presenter), Friebert S, Needle JS, Thompkins JD, Grossoehme D, Jiang J, Wang J, Lyon ME. Oral Presentation. The effect of Family-Centered pediatric Advance Care Planning for Teens with Cancer (FACE®-TC) on adolescents' decisional support, preparedness, and symptoms at 3- and 12- months post-intervention. 54th Congress of the International Society of Paediatric Oncologists (SIOP). September 29, 2022. Barcelona, Spain