Cancer
Conditions
Keywords
psychosocial oncology, symptom management
Brief summary
Sample: The sample will be 298 ethnically diverse (30% Hispanic) survivors who have a new diagnosis or localized recurrence of solid tumor cancer and elevated depression or anxiety and their informal caregivers. Design: The investigators selected the SMART design for this study over alternative designs (e.g.,implementation designs) because the SMART design allows a precision or personalized approach to determine the right treatment at the right dose with the right sequence for the right survivor-caregiver dyad. SMART designs, although newer, show promise in developing the sequences of evidence-based interventions for more efficient and individualized patient- and caregiver-centered care. The investigators will use findings from this study to create an algorithm for clinically meaningful decision making about symptom management for survivors and their caregivers to be tested in future implementation/dissemination studies. The dyad (survivor-caregiver) will be randomly assigned to either: 1) Symptom Management and Survivorship Guideline (Handbook) alone or 2) Telephone Interpersonal Counseling (TIP-C) +Handbook for 8 weeks followed by continued Handbook alone for 4 weeks. During 12 weeks following initial randomization, all participants will receive weekly telephone contacts to assess symptoms, deliver the assigned intervention and assess its enactment and fidelity. After the initial 4 weeks in the Handbook alone group, the survivor's response to the intervention will be determined. If the survivor responds (defined as a reduced score on depression and/or anxiety), the dyad will continue with the Handbook alone for 8 more weeks. If the survivor is a non-responder (defined as no improvement or a worsening score for depression and/or anxiety), the dyad will be re-randomized to either continue with Handbook alone for 8 more weeks, or add 8 weeks of TIP-C. Outcomes will be assessed at baseline, weeks 13 and 17 for both members of the dyad.
Detailed description
Informal caregivers, typically family members or friends, provide more than half of the care needed for the 5.7 million cancer survivors (defined as individuals from diagnosis to end-of-life) in the United States, often with negative consequences to their health. Caregivers assist with the management of the survivor's symptoms such as fatigue, pain and insomnia, and others.Psychological distress (depression and anxiety) has been reported in at least 30% of survivors and their caregivers who are not always prepared for the task of symptom management. This research assists both the caregiver and survivor (the dyad in this study) to manage the survivor's cancer- and treatment-related symptoms and the distress of both members of the dyad in a sample of 298 survivors with elevated depression or anxiety and their 298 caregivers. Dyads will be recruited during the survivor's chemotherapy or targeted therapy for a solid tumor, a time when symptom burden and psychological distress are particularly high. The investigators will use two evidence-based interventions extensively tested against active and passive controls in traditional randomized controlled trials (RCTs). While overall efficacy of these interventions has been established, individuals differ in their responses. When an intervention does not initially work, clinical logic is to either extend the timeframe or prescribe a different intervention. Yet, these alternatives are seldom tested and not evidence-based. The proposed project advances beyond a traditional RCT of testing fixed one size fits all interventions to the sequential multiple assignment randomized trial (SMART) design to build the evidence base for intervention sequencing that accounts for heterogeneity of responses. The first intervention, a printed symptom management and survivorship handbook (Handbook) with strategies for self-management of symptoms common during chemotherapy will be given to both survivor and caregiver (the dyad). Handbook strategies, if successfully enacted, produce positive symptom responses for the survivor. However, psychological distress of the survivor or the caregiver may diminish the receipt and enactment of the Handbook strategies and also exacerbate the severity of other symptoms which, in turn, produces poor symptom responses. Research by this team has documented dyadic effects where survivors' psychosocial distress impacts that of the caregiver and vice versa. The survivor's and caregiver's distress exhibit similar trajectories. Therefore, the second intervention tested in sequencing is the 8-week telephone interpersonal counseling intervention (TIP-C) to manage psychological distress of the dyad. The dyad (survivor-caregiver) will be randomly assigned to either: 1) Symptom Management and Survivorship Guideline (Handbook) alone or 2) Telephone Interpersonal Counseling (TIP-C) +Handbook for 8 weeks followed by continued Handbook alone for 4 weeks. During 12 weeks following initial randomization, all participants will receive weekly telephone contacts to assess symptoms, deliver the assigned intervention and assess its enactment and fidelity. After the initial 4 weeks in the Handbook alone group, the survivor's response to the intervention will be determined. If the survivor responds (defined as a reduced score on depression and/or anxiety), the dyad will continue with the Handbook alone for 8 more weeks. If the survivor is a non-responder (defined as no improvement or a worsening score for depression and/or anxiety), the dyad will be re-randomized to either continue with Handbook alone for 8 more weeks, or add 8 weeks of TIP-C. Outcomes will be assessed at baseline, weeks 13 and 17 for both members of the dyad. The following specific aims will be tested. 1. Determine if dyads in the TIP-C+Handbook as compared to the Handbook alone group created by the first randomization will have: a) lower depression, anxiety, and summed severity of 13 other symptoms at weeks 1-12, 13, and 17 (primary outcomes); b) lower use of healthcare services (hospitalizations, urgent care or emergency department \[ED\] visits) during 17 weeks (secondary outcomes); c) greater self-efficacy, social support, and lower caregiver burden during weeks 13 and 17 (potential mediators). 2. Among non-responders to the Handbook alone after 4 weeks, determine if dyads in TIP-C+Handbook as compared to the Handbook alone group created by the second randomization will have better primary and secondary outcomes and potential mediators at weeks 5-12, 13, and 17. 3. Test the interdependence in survivors' and caregivers' primary and secondary outcomes. 4. Determine which characteristics of the dyad are associated with responses to the Handbook alone during weeks 1-4 and optimal outcomes for the dyad during weeks 1-12, 13 and 17 so as to determine tailoring variables for the decision rules of individualized sequencing of interventions in the future.
Interventions
BEHAVIORALHandbook
see arm/group descriptions
BEHAVIORALTIP-C plus Handbook
see arm/group descriptions
Sponsors
National Cancer Institute (NCI)
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Masking description
Follow-up data collectors will be blind to the arm of the study.
Intervention model description
This project will determine which dyads require which intervention sequence: Handbook alone, Handbook alone stepped up with Telephone Interpersonal Counseling (TIP-C) based on demonstrated needs after giving Handbook alone 4 weeks of time, or an combined TIP-C+Handbook for the first 8 weeks then Handbook alone for 4 weeks. Dyads will be initially randomized to either Handbook alone or TIP-C+Handbook. If the survivor's depression or anxiety does not respond to Handbook alone at week 4, dyads will be re-randomized to the TIPC+Handbook or continue with Handbook alone. Outcome data will be collected at baseline, weeks 13 (post-intervention) and 17 (follow-up). Total duration is 17 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria for the survivors are: 1) age 18 or older; 2) undergoing chemotherapy, hormonal therapy, or targeted therapy for a solid tumor cancer; 3) able to perform basic activities of daily living; 4) cognitively oriented to time, place, and person (determined by recruiter); 5) reporting severity of \>2 on depression or \>4 on anxiety using a 0-10 standardized scale; 6) able to speak and understand English or Spanish; 7) access to a telephone and 8) has a caregiver who can be in any relationship role (e.g., spouse, sibling, parent, friend) who can participate with them. Inclusion criteria for the caregivers are: 1) age 18 or older; 2) able to speak and understand English or Spanish; 3) access to a telephone; 4) not currently receiving counseling and/or psychotherapy; and 5) not currently treated for cancer.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Weeks 1-13 and week 17 | Symptoms were measured using the modified General Symptom Distress Scale (GSDS), a brief instrument that measures 18 common symptoms fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicate severity of each symptom on the scale from 0=not present to 10=worst possible. A summed symptom severity index for 16 symptoms other than depression and anxiety was computed by adding severities of 16 symptoms at each weekly contact (weeks 1-12) and week 13 interview for the immediate effects. The summed symptom severity range is 0-160, a higher score reflects a worse outcome. Week 17 value of the index was analyzed to determine the sustained effects. |
| Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Weeks 5-13 and week 17 | Symptoms were measured using the modified General Symptom Distress Scale (GSDS), a brief instrument that measures 18 common symptoms fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicate severity of each symptom on the scale from 0=not present to 10=worst possible. A summed symptom severity index for 16 symptoms other than depression and anxiety was computed by adding severities of 16 symptoms at each weekly contact (weeks 5-12) and week 13 interview for the immediate effects. The summed symptom severity range is 0-160, a higher score reflects a worse outcome. Week 17 value of the index was analyzed to determine the sustained effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 and week 17 | Measured using Center for Epidemiological Studies- Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms). |
| Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 and week 17 | Measured using Center for Epidemiological Studies- Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms). |
| Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 and week 17 | Measured using Patient-Reported Outcomes Measurement Information System (PROMIS)-Anxiety 8a short form. Each question is rated on a five-point scale from 1=Never to 5=Always. The lowest possible raw score is 8; the highest possible raw score is 40. Raw scores are converted into t-scores with potential range of 37.1 to 83.1. Higher scores indicate greater anxiety. The mean of the US general population is 50 with standard deviation 10. Consensus-based but not data-based thresholds for scores in cancer populations are 50 for mildly symptomatic, 60 for moderately symptomatic, and 70 for severely symptomatic. |
| Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 and week 17 | Measured using Patient-Reported Outcomes Measurement Information System (PROMIS)-Anxiety 8a short form. Each question is rated on a five-point scale from 1=Never to 5=Always. The lowest possible raw score is 8; the highest possible raw score is 40. Raw scores are converted into t-scores with potential range of 37.1 to 83.1. Higher scores indicate greater anxiety. The mean of the US general population is 50 with standard deviation 10. Consensus-based but not data-based thresholds for scores in cancer populations are 50 for mildly symptomatic, 60 for moderately symptomatic, and 70 for severely symptomatic. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the University of Arizona Cancer Center in Tucson and Phoenix, AZ, Valleywise Health, a federally qualified health center in Phoenix, AZ, and the community. Recruitment took place between January 16, 2019, and January 1, 2022. Research recruiters approached survivors at clinic visits, explained the study, and answered questions. Recruiters determined eligibility and followed protocol for consenting both the survivor and caregiver.
Pre-assignment details
908 (N= 451 survivors, N=457 caregivers) consented. 59 caregivers dropped before baseline. 398 dyads (survivor and caregiver) were interviewed at baseline. 24 dyads were not randomized due to the following: caregivers with no survivor interview (N=15), survivor ineligible (N=2), could not be reached (N=6), and other (N=1). 374 dyads were randomized into one of two groups: Symptom Management and Survivorship Handbook (SMSH) (N=277), and Telephone Interpersonal Counseling (TIP-C) + SMSH (N=97).
Participants by arm
| Arm | Count |
|---|---|
| Survivors-SMSH Alone for 4 Weeks, Depression/Anxiety Responders Continued With SMSH Alone Weeks 5-12 The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, survivors and caregivers were referred for symptom self-management. After 4 weeks, depression or anxiety responders in the SMSH alone group continued with the SMSH alone for weeks 5-12. Depression or anxiety responders are survivors who started at severe at onset and ended at moderate or mild at a given time point (e.g., week 4), and survivors who started at moderate and ended at mild. At week 13, the survivor and caregiver were each called to complete the second assessment and at week 17 they were called to complete the third and final assessment. | 166 |
| Survivors-SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH Alone Weeks 5-12 The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, the survivors were referred for symptom self-management. After 4 weeks, depression or anxiety non-responders in the SMSH alone group were rerandomized (as a dyad) to either continue the SMSH alone for 8 weeks or add TIPC for 8 weeks. Depression or anxiety non-responders are survivors who do not respond to either or both depression or anxiety symptoms. Depression or anxiety responders started at severe at onset and ended at moderate or mild at a given time point (e.g., week 4), and survivors who started at moderate and ended at mild. At week 13, the survivor and caregiver were each called to complete the second assessment and at week 17 they were called to complete the third and final assessment. | 44 |
| Survivors- SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH+TIPC Weeks 5-12 The Symptom Management and Survivorship Handbook (SMSH) is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom, and resources. The SMSH was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, dyads were referred for symptom self-management. After 4 weeks, depression or anxiety non-responders in the SMSH alone group were rerandomized (as a dyad) to either continue the SMSH alone for 8 weeks or add TIPC for 8 weeks. Depression or anxiety non-responders are survivors who do not respond to either or both depression or anxiety symptoms. Depression or anxiety responders started at severe at onset and ended at moderate or mild at week 4, and survivors who started at moderate and ended at mild. The Telephone Interpersonal Counseling (TIPC) 8-week protocol was the same for both survivor and caregiver. During weekly contact, counselors targeted social support behaviors using interpersonal communication techniques. Counselors personalized the counseling intervention for the specific needs or interests as expressed during sessions while still adhering to a structured protocol. At week 13, the survivor and caregiver were each called to complete the second assessment. At week 17 they were called to complete the final assessment. | 44 |
| Survivors SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12 The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, the survivors were referred for symptom self-management. In addition to the SMSH, each survivor and caregiver received one 40-minute telephone call per week for 12 weeks. The Telephone Interpersonal Counseling (TIP-C) intervention 8-week protocol was the same for both survivor and caregiver. During weekly contacts, the counselors targeted social support behaviors using interpersonal communications techniques. Counselors personalized the counseling intervention for the specific needs or interests as expressed during sessions while still adhering to a structured protocol. The final 4 weeks were Handbook only. | 97 |
| Caregivers- SMSH Alone for 4 Weeks, Depression/Anxiety Responders Continued w/ SMSH Alone Weeks 5-12 The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, survivors and caregivers were referred for symptom self-management. After 4 weeks, depression or anxiety responders in the SMSH alone group continued with the SMSH alone for weeks 5-12. Depression or anxiety responders are survivors who started at severe at onset and ended at moderate or mild at a given time point (e.g., week 4), and survivors who started at moderate and ended at mild. At week 13, the survivor and caregiver were each called to complete the second assessment and at week 17 they were called to complete the third and final assessment. | 166 |
| Caregivers-SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH Alone Weeks 5-12 The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, the survivors were referred for symptom self-management. After 4 weeks, depression or anxiety non-responders in the SMSH alone group were rerandomized (as a dyad) to either continue the SMSH alone for 8 weeks or add TIPC for 8 weeks. Depression or anxiety non-responders are survivors who do not respond to either or both depression or anxiety symptoms. Depression or anxiety responders started at severe at onset and ended at moderate or mild at a given time point (e.g., week 4), and survivors who started at moderate and ended at mild. At week 13, the survivor and caregiver were each called to complete the second assessment and at week 17 they were called to complete the third and final assessment. | 44 |
| Caregivers-SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH+TIPC Weeks 5-12 The Symptom Management and Survivorship Handbook (SMSH) is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom, and resources. The SMSH was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, dyads were referred for symptom self-management. After 4 weeks, depression or anxiety non-responders in the SMSH alone group were rerandomized (as a dyad) to either continue the SMSH alone for 8 weeks or add TIPC for 8 weeks. Depression or anxiety non-responders are survivors who do not respond to either or both depression or anxiety symptoms. Depression or anxiety responders started at severe at onset and ended at moderate or mild at week 4, and survivors who started at moderate and ended at mild. The Telephone Interpersonal Counseling (TIPC) 8-week protocol was the same for both survivor and caregiver. During weekly contact, counselors targeted social support behaviors using interpersonal communication techniques. Counselors personalized the counseling intervention for the specific needs or interests as expressed during sessions while still adhering to a structured protocol. At week 13, the survivor and caregiver were each called to complete the second assessment. At week 17 they were called to complete the final assessment. | 44 |
| Caregivers- SMSH+ TIPC The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, the survivors were referred for symptom self-management. In addition to the SMSH, each survivor and caregiver received one 40-minute telephone call per week for 12 weeks. The Telephone Interpersonal Counseling (TIP-C) intervention 8-week protocol was the same for both survivor and caregiver. During weekly contacts, the counselors targeted social support behaviors using interpersonal communications techniques. Counselors personalized the counseling intervention for the specific needs or interests as expressed during sessions while still adhering to a structured protocol. The final 4 weeks were Handbook only. | 97 |
| Survivor Drop-outs From SMSH Alone Prior to Week 4 The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom, and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, survivors and caregivers were referred for symptom self-management. These participants were lost to attrition prior to the week 4 assessment for response or non-response. | 23 |
| Caregiver Drop-outs From SMSH Alone Prior to Week 4 The Symptom Management and Survivorship Handbook is a self-care management handbook with each symptom chapter presented in an identical format: what the symptom is, how people describe the symptom, the causes of the symptom, strategies for managing the symptom, and resources. The Handbook was available in English and Spanish. Each weekly call began with a symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, survivors and caregivers were referred for symptom self-management. These participants were lost to attrition prior to the week 4 assessment for response or non-response. | 23 |
| Total | 748 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 5 | 3 | 1 | 4 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 2 | 1 | 1 | 0 | 1 | 4 | 13 | 13 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 4 | 5 | 5 | 2 | 2 | 5 | 9 | 10 |
Baseline characteristics
| Characteristic | Caregivers- SMSH Alone for 4 Weeks, Depression/Anxiety Responders Continued w/ SMSH Alone Weeks 5-12 | Caregivers-SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH Alone Weeks 5-12 | Caregivers-SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH+TIPC Weeks 5-12 | Caregivers- SMSH+ TIPC | Survivor Drop-outs From SMSH Alone Prior to Week 4 | Caregiver Drop-outs From SMSH Alone Prior to Week 4 | Total | Survivors-SMSH Alone for 4 Weeks, Depression/Anxiety Responders Continued With SMSH Alone Weeks 5-12 | Survivors-SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH Alone Weeks 5-12 | Survivors- SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH+TIPC Weeks 5-12 | Survivors SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.98 years STANDARD_DEVIATION 16.04 | 54.14 years STANDARD_DEVIATION 15.56 | 56.25 years STANDARD_DEVIATION 16.07 | 53.89 years STANDARD_DEVIATION 3.46 | 60.08 years STANDARD_DEVIATION 14.43 | 52.56 years STANDARD_DEVIATION 16.52 | 57.06 years STANDARD_DEVIATION 13.45 | 59.48 years STANDARD_DEVIATION 11.86 | 61.61 years STANDARD_DEVIATION 12.28 | 59.09 years STANDARD_DEVIATION 13.77 | 60.44 years STANDARD_DEVIATION 12.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 78 Participants | 17 Participants | 16 Participants | 43 Participants | 10 Participants | 11 Participants | 318 Participants | 71 Participants | 17 Participants | 13 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 27 Participants | 28 Participants | 53 Participants | 13 Participants | 12 Participants | 428 Participants | 95 Participants | 27 Participants | 30 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 37 Participants | 9 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 14 Participants | 3 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 36 Participants | 8 Participants | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 44 Participants | 14 Participants | 14 Participants | 26 Participants | 7 Participants | 8 Participants | 214 Participants | 49 Participants | 12 Participants | 10 Participants | 30 Participants |
| Race (NIH/OMB) White | 94 Participants | 26 Participants | 26 Participants | 62 Participants | 12 Participants | 11 Participants | 436 Participants | 94 Participants | 29 Participants | 28 Participants | 54 Participants |
| Sex: Female, Male Female | 112 Participants | 30 Participants | 34 Participants | 59 Participants | 16 Participants | 17 Participants | 541 Participants | 124 Participants | 38 Participants | 33 Participants | 78 Participants |
| Sex: Female, Male Male | 54 Participants | 14 Participants | 10 Participants | 38 Participants | 7 Participants | 6 Participants | 207 Participants | 42 Participants | 6 Participants | 11 Participants | 19 Participants |
| Symptom Severity | 19.73 units on a scale STANDARD_DEVIATION 18 | 22.00 units on a scale STANDARD_DEVIATION 18.47 | 19.39 units on a scale STANDARD_DEVIATION 16.31 | 20.61 units on a scale STANDARD_DEVIATION 17.51 | 51.17 units on a scale STANDARD_DEVIATION 26.01 | 21.17 units on a scale STANDARD_DEVIATION 23.37 | 30.43 units on a scale STANDARD_DEVIATION 23.72 | 34.67 units on a scale STANDARD_DEVIATION 22.28 | 43.55 units on a scale STANDARD_DEVIATION 23.51 | 48.02 units on a scale STANDARD_DEVIATION 30.12 | 43.53 units on a scale STANDARD_DEVIATION 22.92 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 166 | 3 / 44 | 1 / 44 | 4 / 97 | 0 / 166 | 0 / 44 | 0 / 44 | 0 / 97 | 1 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 166 | 0 / 44 | 0 / 44 | 0 / 97 | 0 / 166 | 0 / 44 | 0 / 44 | 0 / 97 | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 166 | 0 / 44 | 0 / 44 | 0 / 97 | 0 / 166 | 0 / 44 | 0 / 44 | 0 / 97 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Symptom Severity Index- Comparison of Two Groups Created by First Randomization
Symptoms were measured using the modified General Symptom Distress Scale (GSDS), a brief instrument that measures 18 common symptoms fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicate severity of each symptom on the scale from 0=not present to 10=worst possible. A summed symptom severity index for 16 symptoms other than depression and anxiety was computed by adding severities of 16 symptoms at each weekly contact (weeks 1-12) and week 13 interview for the immediate effects. The summed symptom severity range is 0-160, a higher score reflects a worse outcome. Week 17 value of the index was analyzed to determine the sustained effects.
Time frame: Weeks 1-13 and week 17
Population: Out of 374 dyads (survivors and caregivers), 277 were randomized initially to the SMSH alone, and 97 to SMSH+TIPC.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Survivors- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Average over weeks 1-13 | 26.28 units on a scale | Standard Error 0.6 |
| Survivors- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Week 17 | 25.72 units on a scale | Standard Error 1.07 |
| Survivors- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Week 17 | 26.30 units on a scale | Standard Error 1.78 |
| Survivors- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Average over weeks 1-13 | 26.55 units on a scale | Standard Error 0.98 |
| Caregivers- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Average over weeks 1-13 | 12.02 units on a scale | Standard Error 0.4 |
| Caregivers- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Week 17 | 10.16 units on a scale | Standard Error 0.74 |
| Caregivers- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Average over weeks 1-13 | 11.19 units on a scale | Standard Error 0.65 |
| Caregivers- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Week 17 | 9.04 units on a scale | Standard Error 1.15 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. The adjusted effect size d=0.54 between the SMSH alone group and SMSH+TIPC group was detectable with power of .94 in two-sided tests at .05 level of significance.p-value: 0.8195% CI: [-2.5, 1.96]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. The adjusted effect size d=0.54 between the SMSH alone group and SMSH+TIPC group was detectable with power of .94 in two-sided tests at .05 level of significance.p-value: 0.7895% CI: [-4.65, 3.49]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. The adjusted effect size d=0.54 between the SMSH alone group and SMSH+TIPC group was detectable with power of .94 in two-sided tests at .05 level of significance.p-value: 0.2795% CI: [-0.66, 2.32]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. The adjusted effect size d=0.54 between the SMSH alone group and SMSH+TIPC group was detectable with power of .94 in two-sided tests at .05 level of significance.p-value: 0.1995% CI: [-0.88, 4.39]Mixed Models Analysis
Primary
Symptom Severity Index- Comparison of Two Groups Created by Second Randomization
Symptoms were measured using the modified General Symptom Distress Scale (GSDS), a brief instrument that measures 18 common symptoms fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicate severity of each symptom on the scale from 0=not present to 10=worst possible. A summed symptom severity index for 16 symptoms other than depression and anxiety was computed by adding severities of 16 symptoms at each weekly contact (weeks 5-12) and week 13 interview for the immediate effects. The summed symptom severity range is 0-160, a higher score reflects a worse outcome. Week 17 value of the index was analyzed to determine the sustained effects.
Time frame: Weeks 5-13 and week 17
Population: Survivors and caregivers randomized for the second time after survivor's non-response to the SMSH alone after 4 weeks.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Survivors- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Average over weeks 5-13 | 33.67 units on a scale | Standard Error 1.73 |
| Survivors- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Week 17 | 37.84 units on a scale | Standard Error 2.73 |
| Survivors- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Week 17 | 35.86 units on a scale | Standard Error 2.82 |
| Survivors- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Average over weeks 5-13 | 34.14 units on a scale | Standard Error 1.75 |
| Caregivers- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Average over weeks 5-13 | 14.50 units on a scale | Standard Error 1.36 |
| Caregivers- SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Week 17 | 15.22 units on a scale | Standard Error 1.95 |
| Caregivers- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Average over weeks 5-13 | 12.53 units on a scale | Standard Error 1.37 |
| Caregivers- SMSH+ TIPC | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Week 17 | 11.92 units on a scale | Standard Error 1.96 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. . The adjusted effect size (Cohen's d=0.54) was used to power comparisons on the primary outcomes reported by groups from the second randomization. This analysis indicated that 60 per group would be required for power of .80 or greater in two-sided tests at α= 0.05.p-value: 0.5395% CI: [-3.3, 6.36]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. . The adjusted effect size (Cohen's d=0.54) was used to power comparisons on the primary outcomes reported by groups from the second randomization. This analysis indicated that 60 per group would be required for power of .80 or greater in two-sided tests at α= 0.05.p-value: 0.9795% CI: [-5.7, 9.68]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. . The adjusted effect size (Cohen's d=0.54) was used to power comparisons on the primary outcomes reported by groups from the second randomization. This analysis indicated that 60 per group would be required for power of .80 or greater in two-sided tests at α= 0.05.p-value: 0.3195% CI: [-1.83, 5.75]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. The adjusted effect size (Cohen's d=0.54) was used to power comparisons on the primary outcomes reported by groups from the second randomization. This analysis indicated that 60 per group would be required for power of .80 or greater in two-sided tests at α= 0.05.p-value: 0.6195% CI: [-2.13, 8.74]Mixed Models Analysis
Secondary
Anxiety Symptoms- Comparison of Two Groups Created by First Randomization
Measured using Patient-Reported Outcomes Measurement Information System (PROMIS)-Anxiety 8a short form. Each question is rated on a five-point scale from 1=Never to 5=Always. The lowest possible raw score is 8; the highest possible raw score is 40. Raw scores are converted into t-scores with potential range of 37.1 to 83.1. Higher scores indicate greater anxiety. The mean of the US general population is 50 with standard deviation 10. Consensus-based but not data-based thresholds for scores in cancer populations are 50 for mildly symptomatic, 60 for moderately symptomatic, and 70 for severely symptomatic.
Time frame: Week 13 and week 17
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Survivors- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 48.98 T-score | Standard Error 0.54 |
| Survivors- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 49.11 T-score | Standard Error 0.54 |
| Survivors- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 50.91 T-score | Standard Error 0.9 |
| Survivors- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 50.86 T-score | Standard Error 0.9 |
| Caregivers- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 47.72 T-score | Standard Error 0.5 |
| Caregivers- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 47.58 T-score | Standard Error 0.5 |
| Caregivers- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 47.58 T-score | Standard Error 0.83 |
| Caregivers- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 46.89 T-score | Standard Error 0.82 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.0695% CI: [-3.98, 0.19]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.0995% CI: [-3.81, 0.11]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.8995% CI: [-1.77, 2.04]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.4795% CI: [-1.2, 2.58]Mixed Models Analysis
Secondary
Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization
Measured using Patient-Reported Outcomes Measurement Information System (PROMIS)-Anxiety 8a short form. Each question is rated on a five-point scale from 1=Never to 5=Always. The lowest possible raw score is 8; the highest possible raw score is 40. Raw scores are converted into t-scores with potential range of 37.1 to 83.1. Higher scores indicate greater anxiety. The mean of the US general population is 50 with standard deviation 10. Consensus-based but not data-based thresholds for scores in cancer populations are 50 for mildly symptomatic, 60 for moderately symptomatic, and 70 for severely symptomatic.
Time frame: Week 13 and week 17
Population: Survivors and caregivers randomized for the second time after survivor's non-response to the SMSH alone after 4 weeks.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Survivors- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 52.90 T-score | Standard Error 1.32 |
| Survivors- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 55.75 T-score | Standard Error 1.35 |
| Survivors- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 55.48 T-score | Standard Error 1.4 |
| Survivors- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 54.31 T-score | Standard Error 1.39 |
| Caregivers- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 50.47 T-score | Standard Error 1.31 |
| Caregivers- SMSH Alone | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 49.45 T-score | Standard Error 1.3 |
| Caregivers- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 49.92 T-score | Standard Error 1.3 |
| Caregivers- SMSH+ TIPC | Anxiety Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 49.77 T-score | Standard Error 1.3 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.4595% CI: [-5.22, 2.39]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.8295% CI: [-3.59, 4.12]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.7795% CI: [-3.13, 4.23]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.8695% CI: [-3.98, 3.34]Mixed Models Analysis
Secondary
Depressive Symptoms- Comparison of Two Groups Created by First Randomization
Measured using Center for Epidemiological Studies- Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms).
Time frame: Week 13 and week 17
Population: Survivors and caregivers included in the first randomization
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Survivors- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 12.90 units on a scale | Standard Error 0.59 |
| Survivors- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 13.60 units on a scale | Standard Error 0.6 |
| Survivors- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 13.67 units on a scale | Standard Error 0.98 |
| Survivors- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 13.78 units on a scale | Standard Error 0.97 |
| Caregivers- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 10.48 units on a scale | Standard Error 0.49 |
| Caregivers- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 9.94 units on a scale | Standard Error 0.49 |
| Caregivers- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 13 | 10.44 units on a scale | Standard Error 0.83 |
| Caregivers- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by First Randomization | Week 17 | 9.62 units on a scale | Standard Error 0.82 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.4495% CI: [-3.12, 1.35]Regression, Linear
Comparison: The key parameter was the coefficient for the trial arm difference at week 17 in linear mixed effects model.p-value: 0.9595% CI: [-2.32, 2.18]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.9795% CI: [-1.85, 1.93]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.7495% CI: [-1.56, 2.2]Mixed Models Analysis
Secondary
Depressive Symptoms- Comparison of Two Groups Created by Second Randomization
Measured using Center for Epidemiological Studies- Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms).
Time frame: Week 13 and week 17
Population: Survivors and caregivers randomized for the second time after survivor's non-response to the SMSH alone after 4 weeks.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Survivors- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 19.21 units on a scale | Standard Error 1.57 |
| Survivors- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 20.34 units on a scale | Standard Error 1.58 |
| Survivors- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 21.24 units on a scale | Standard Error 1.67 |
| Survivors- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 19.17 units on a scale | Standard Error 1.65 |
| Caregivers- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 11.60 units on a scale | Standard Error 1.29 |
| Caregivers- SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 12.67 units on a scale | Standard Error 1.27 |
| Caregivers- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 13 | 13.60 units on a scale | Standard Error 1.29 |
| Caregivers- SMSH+ TIPC | Depressive Symptoms- Comparison of Two Groups Created by Second Randomization | Week 17 | 12.46 units on a scale | Standard Error 1.29 |
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.9895% CI: [-4.49, 4.58]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.795% CI: [-5.48, 3.68]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.2795% CI: [-5.62, 1.62]Mixed Models Analysis
Comparison: The null hypothesis was that the means of two groups were equal. The alternative hypothesis was that the means of two groups were not equal. Sample size was determined by the power calculation for the primary outcome.p-value: 0.9195% CI: [-3.4, 3.81]Mixed Models Analysis