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 is available in English and Spanish. Each weekly call will begin with the symptom assessment. For each symptom rated at 4 or higher on a 0-10 scale of severity, the survivors will be referred for symptom self-management. During weeks 2-12, Handbook use since the last call (intervention enactment) and symptoms will be assessed. During weekly calls to caregivers, the caregivers will be notified of symptoms above threshold experienced by survivors and directed to the Handbook. During weeks 2-12, Handbook use and symptoms are assessed, a summary of survivors' symptoms provided. Calls will last about 10 minutes.

Each survivor and caregiver will receive one 40-minute telephone call per week for 12 weeks. The Telephone Interpersonal Counseling (TIP-C) intervention 8-week protocol is the same for both survivor and caregiver. During weekly contacts, the counselors target social support behaviors using interpersonal communications techniques. Counselors can personalize the counseling intervention for the specific needs or interests as expressed during sessions while still adhering to a structured protocol. The final 4 weeks will be Handbook only.

Handbook

TIP-C plus Handbook

Terry Badger, PhD

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.

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.

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.

Follow-up data collectors will be blind to the arm of the study.

Caregivers' and Cancer Survivors' Psychological Distress & Symptom Management

Improving Informal Caregivers' and Cancer Survivors' Psychological Distress, Symptom Management and Health Care Use

The investigators will share the findings and data with other researchers, the public, and key stakeholders based on the principles that NIH has articulated regarding the sharing of study results and resources. The University of Arizona agrees that data sharing is essential for expedited translation of research results into knowledge, products, and procedures to improve health.

Sharing of study results Manuscript based on results from the proposed study will be published in peer-reviewed journals. The investigators will select "open access" options for these manuscripts whenever possible.

Data Sharing Data from this study will be available to other researchers under the following conditions: 1) appropriate human subjects protection is in place; 2) data have been de-identified; and 3) study investigators have publicly presented and published key findings. Data and safety monitoring plan is described under Human Subjects.

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.

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.

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).

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.

National Cancer Institute (NCI)

University of Arizona

Adverse events/serious adverse events were identified during the implementation of the experimental protocols and were monitored by the Investigators in several ways: 1) Interviewers could identify both serious adverse events and/or adverse events during the completion of telephone interviews or telephone calls to schedule telephone interviews; 2) The interventionists could identify both serious adverse events and/or adverse events during their telephone contacts with the participants.

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.

Survivors- SMSH Alone for 4 Weeks, Depression/Anxiety Responders Continued With SMSH Alone Week 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.

Survivors-SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH Alone 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.

Survivors- SMSH Alone for 4 Weeks, Depression/Anxiety Non-responders Continued SMSH+TIPC 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. 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.

Survivors SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12

Caregivers-SMSH Alone for 4 Weeks, Depression/Anxiety Responders Continued

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 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, 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.

Survivor Drop-outs From SMSH Alone Prior to Week 4

Caregiver Drop-outs From SMSH Alone Prior to Week 4

Survivors-SMSH Alone for 4 Weeks, Depression/Anxiety Responders Continued With SMSH Alone Weeks 5-12

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+TIPC Weeks 5-12

Caregivers- SMSH+ TIPC

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Symptoms were measured using the General Symptom Distress Scale (GSDS) assessment of 18 symptoms: fatigue, sleep difficulty, 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 indicated the severity of each symptom (0= not present, 10= worst possible). A summed symptom severity index for 16 symptoms other than depression and anxiety was derived. The potential range is 0-160, a higher score reflects a worse outcome.

Symptom Severity

The larger than planned number of survivor-caregiver dyads with survivors responding to SMSH alone resulted in larger than planned number of participants in the first randomization and smaller number in the second randomization. There was a larger than planned number of responders to SMSH alone after 4 weeks.

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.

Average over weeks 1-13

Week 17

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. During weeks 2-12, Handbook use since the last call (intervention enactment) and symptoms were assessed. During weekly calls to caregivers, the caregivers were notified of symptoms above the threshold experienced by survivors and directed to the Handbook. During weeks 2-12, Handbook use and symptoms were assessed, and a summary of survivors' symptoms was provided. Calls lasted about 10 minutes.

Handbook: see arm/group descriptions

Survivors- SMSH Alone

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.

TIP-C plus Handbook: see arm/group descriptions

Survivors- 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. During weeks 2-12, Handbook use since the last call (intervention enactment) and symptoms were assessed. During weekly calls to caregivers, the caregivers were notified of symptoms above the threshold experienced by survivors and directed to the Handbook. During weeks 2-12, Handbook use and symptoms were assessed, and a summary of survivors' symptoms was provided. The calls lasted about 10 minutes.

Caregivers- SMSH Alone

Out of 374 dyads (survivors and caregivers), 277 were randomized initially to the SMSH alone, and 97 to SMSH+TIPC.

Symptom Severity Index- Comparison of Two Groups Created by First Randomization

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.

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.

Average over weeks 5-13

Survivors and caregivers randomized for the second time after survivor's non-response to the SMSH alone after 4 weeks.

Symptom Severity Index- Comparison of Two Groups Created by Second Randomization

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.

The key parameter was the coefficient for the trial arm difference at week 17 in linear mixed effects model.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Caregivers' and Cancer Survivors' Psychological Distress & Symptom Management	NCT03743415	Cancer	Handbook TIP-C plus Hand...	18 Years -	University of Arizona
Caregivers' and Cancer Survivors' Psychological Distress & Symptom Management	NCT03743415	Cancer	Handbook TIP-C plus Hand...	18 Years -	University of Arizona

Spots Global Cancer Trial Database for handbook

Every month we try and update this database with for handbook cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for handbook

Every month we try and update this database with for handbook cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for handbook cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.