Cancer
Conditions
Keywords
Chemotherapy, symptom management
Brief summary
Survivors of solid tumors (N=451) who completed curative intent chemotherapy for a solid tumor within the past 2 years were interviewed at baseline and stratified as high or low need for symptom management based on comorbidity and depressive symptoms. High need survivors were randomized initially to the 12-week Symptom Management and Survivorship Handbook (SMSH, N=282) or 12-week SMSH Telephone Interpersonal Counseling (TIPC, N=93) added during weeks 1-8. After 4 weeks of the SMSH alone, non-responders on depression were re-randomized to continue with SMSH alone (N=30) or add TIPC (N=31).
Detailed description
Nearly 15.5 million Americans have survived cancer and virtually all have experienced symptoms from cancer treatment. Numerous symptom management interventions have been tested during active treatment, yet few have addressed the continuing fatigue, pain, depression, etc. that endure following the end of treatment. Existing post-treatment symptom management research has targeted survivors months after the end of active treatment, overlooking the immediate post-treatment period. During this period, some survivors have their symptoms resolve naturally (low need for intervention), while others suffer from high symptom burden (high need for intervention), with 30% experiencing depression. Sample: Survivors of solid tumors (N=451) who completed curative intent chemotherapy for a solid tumor within the past 2 years. Design: The SMART design incorporates two interventions with proven efficacy and addresses heterogeneity of survivors' responses by following the clinical logic of starting with one intervention, assessing its success, and continuing it when effective. High need survivors will be initially randomized to receive 1) weekly symptom assessment with referral for elevated symptoms to a printed Symptom Management and Survivorship Handbook (SMSH) or 2) a more intensive intervention adding Telephone Interpersonal Counselling (TIPC) to the SMSH. After 4 weeks, non-responders to SMSH alone on depression were re-randomized to continue SMSH for 8 more weeks to allow for symptom resolution, or TIPC added for the remaining 8 weeks. The primary outcome was symptom severity index, secondary outcome was depressive symptoms. The hypotheses tests included comparisons of primary and secondary outcomes according tp first randomization and second randomization for non-responders.
Interventions
BEHAVIORALStart with SMSH+TIPC
See arm/group descriptions
BEHAVIORALStart with SMSH alone
See arm/group descriptions
Sponsors
Michigan State University
National Cancer Institute (NCI)
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Masking description
Data collectors will be blinded to the arm of the study.
Intervention model description
Following baseline, symptom management need (high versus low need) will be determined. The low need group will not receive interventions, but will be followed at week 4 for a brief symptom assessment and at week 13. The high need group will be randomly assigned to either: 1) SMSH alone or 2) TIP-C+SMSH for 8 weeks followed by continued 4 weeks of SMSH alone. We will mail the SMSH, printed in the survivor's preferred language, following randomization. All high need participants will receive weekly telephone contacts during weeks 1-12 to assess symptoms, deliver the assigned intervention, and assess intervention enactment and fidelity. After the initial 4 weeks, responders on depression will continue with the SMSH only. Non-responders will re-randomized to either continue with the SMSH alone or add TIP-C. Those initially randomized to TIP-C+SMSH will not be re-randomized. Total duration of each of the three intervention sequences is 12 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Survivors must have a new diagnosis or localized recurrence of solid tumor cancer * Be finishing curative intent adjuvant chemotherapy or chemoradiation, and do not have any subsequent cancer treatments planned, except for radiation therapy, hormonal therapy or trastuzumab for breast cancer. * 18 years of age or older * Have access to a telephone * Understand English or Spanish * Are not currently receiving counseling and/or psychotherapy
Exclusion criteria
* Diagnosis of a psychotic disorder in medical record verified by the recruiter * Nursing home resident * Bedridden * Currently receiving counseling and/or psychotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Severity Index- Comparison of Two Groups Created by First Randomization | Weeks 1-13 | Symptoms were measured using the modified General Symptom Distress Scale (GSDS) allowing for a quick assessment of 18 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 indicated the severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 1-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, with higher score indicating worse outcome (greater severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable. |
| Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | Weeks 5-13 | Symptoms were measured using the modified General Symptom Distress Scale (GSDS) allowing for a quick assessment of 18 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 indicated severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 5-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, higher value reflect worse outcome (greater symptom severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptoms - Comparison of Two Groups Created by Second Randomization | Week 13 | 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 First Randomization. | Week 13 | 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). |
Countries
United States
Participant flow
Recruitment details
Cancer survivors were recruited at a comprehensive cancer center, a federally qualified health center, and community settings in the Southwestern United States. Participants were informed they would be 1) randomized to SMSH or TIPC+SMSH and may be rerandomized after 4 weeks to continue with SMSH alone or add TIPC; 2) telephone assessment and intervention sessions were weekly for 13 weeks; 3) interventions were designed to help reduce symptoms and there were study incentives.
Pre-assignment details
Of 500 consented individuals, 451 had a baseline interview, 71 were low need, 375 were high need and entered into randomization. Five participants were found ineligible. Three participants in the high need group dropped out after baseline before the first randomization. Three participants in the low need group were misclassified initially as high need and were randomized, resulting in 375 randomized and 68 continuing as low need without interventions.
Participants by arm
| Arm | Count |
|---|---|
| Low Need Benchmark or Follow-up In the low need benchmark or follow-up group, participants received baseline and 13-week assessments (about 30-40 minutes) over the telephone. A brief assessment (about 5 minutes) was done at week 4 over the telephone to assess symptoms. Approximately 35% of all participants were in this group. | 71 |
| High Need-SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12 Participants were mailed the printed Symptom Management and Survivorship Handbook (SMSH). The High Need group participant was called every week for 4 weeks to ask about symptoms and suggest strategies from the SMSH to relieve symptoms. Calls were approximately 10 minutes. After 4 weeks, depression responders in the High Need group continued with the SMSH alone for weeks 5-12. Depression 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 participant was called to complete the second assessment. | 204 |
| High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12 Participants were mailed the printed Symptom Management and Survivorship Handbook (SMSH). The High Need group participant was called every week for 4 weeks to ask about symptoms and suggest strategies from the SMSH to relieve symptoms. Calls were approximately 10 minutes. After 4 weeks, depression non-responders were re-randomized to either continue with the SMSH alone for weeks 5-12 or add Telephone Interpersonal Counseling (TIPC) to test the value added by the more intensive intervention. Symptom cases that remained moderate or became severe at week 4 are classified as non-responders. At week 13, the participant was called to complete the second assessment. | 30 |
| High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12 Participants were mailed the printed Symptom Management and Survivorship Handbook (SMSH). The High Need group participant was called every week for 4 weeks to ask about symptoms and suggest strategies from the SMSH to relieve symptoms. Calls were approximately 10 minutes. After 4 weeks, depression non-responders were re-randomized to either continue with the SMSH alone for weeks 5-12 or add Telephone Interpersonal Counseling (TIPC) to test the value added by the more intensive intervention. The TIPC counselor assessed and discussed interpersonal relationships, communication, social support, managing symptoms, and survivorship. Symptom cases that remained moderate or became severe at week 4 are classified as non-responders. At week 13, the participant was called to complete the second assessment. | 31 |
| High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12 Participants were mailed the printed Symptom Management and Survivorship Handbook (SMSH). The High Need group participant was called every week for the first 8 weeks using a combination of Telephone Interpersonal Counseling (TIPC) and SMSH. The TIPC counselor assessed and discussed interpersonal relationships, communication, social support, managing symptoms, and survivorship as well as asked about symptoms and suggest strategies from the SMSH to relieve symptoms. At weeks 9-12, the participant received the SMSH alone. At week 13, the participant was called to complete the second assessment. | 93 |
| Drop-outs From SMSH Alone Prior to Week 4 Participants were mailed the printed Symptom Management and Survivorship Handbook (SMSH). The High Need group participant was called every week for 4 weeks to ask about symptoms and suggest strategies from the SMSH to relieve symptoms. Calls were approximately 10 minutes. These participants were lost to attrition prior to the week 4 assessment for response or non-response. | 17 |
| Total | 446 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 | 3 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 2 | 2 | 14 | 0 |
| Overall Study | Screen failure | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 7 | 0 | 5 | 3 | 17 |
Baseline characteristics
| Characteristic | Low Need Benchmark or Follow-up | High Need-SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12 | High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12 | High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12 | High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12 | Drop-outs From SMSH Alone Prior to Week 4 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.56 years STANDARD_DEVIATION 13.13 | 58.76 years STANDARD_DEVIATION 12.31 | 60.63 years STANDARD_DEVIATION 12.88 | 53.83 years STANDARD_DEVIATION 15.31 | 58.26 years STANDARD_DEVIATION 12.93 | 60.18 years STANDARD_DEVIATION 9.04 | 57.67 years STANDARD_DEVIATION 12.73 |
| Depressive Symptoms | 6.01 units on a scale STANDARD_DEVIATION 4.66 | 13.01 units on a scale STANDARD_DEVIATION 11.08 | 23.35 units on a scale STANDARD_DEVIATION 12.69 | 23.72 units on a scale STANDARD_DEVIATION 2.72 | 16.36 units on a scale STANDARD_DEVIATION 13.42 | 19.25 units on a scale STANDARD_DEVIATION 13.72 | 14.28 units on a scale STANDARD_DEVIATION 11.92 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 39 Participants | 92 Participants | 13 Participants | 13 Participants | 45 Participants | 8 Participants | 210 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 32 Participants | 111 Participants | 17 Participants | 18 Participants | 48 Participants | 9 Participants | 235 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or not reported | 30 Participants | 83 Participants | 10 Participants | 12 Participants | 28 Participants | 4 Participants | 167 Participants |
| Race/Ethnicity, Customized White | 36 Participants | 121 Participants | 19 Participants | 14 Participants | 56 Participants | 11 Participants | 257 Participants |
| Sex/Gender, Customized Female | 49 Participants | 172 Participants | 25 Participants | 25 Participants | 78 Participants | 15 Participants | 364 Participants |
| Sex/Gender, Customized Male | 22 Participants | 32 Participants | 4 Participants | 6 Participants | 14 Participants | 2 Participants | 80 Participants |
| Sex/Gender, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex/Gender, Customized Other | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Symptom Severity | 24.70 units on a scale STANDARD_DEVIATION 20.35 | 36.32 units on a scale STANDARD_DEVIATION 25.48 | 46.97 units on a scale STANDARD_DEVIATION 22.81 | 48.13 units on a scale STANDARD_DEVIATION 26.46 | 37.28 units on a scale STANDARD_DEVIATION 24.65 | 56.06 units on a scale STANDARD_DEVIATION 34.18 | 36.96 units on a scale STANDARD_DEVIATION 24.85 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 1 / 282 | 3 / 93 |
| other Total, other adverse events | 0 / 71 | 0 / 282 | 0 / 93 |
| serious Total, serious adverse events | 0 / 71 | 0 / 282 | 0 / 93 |
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) allowing for a quick assessment of 18 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 indicated the severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 1-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, with higher score indicating worse outcome (greater severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable.
Time frame: Weeks 1-13
Population: Of the 375 high-need survivors initially randomized, 282 received the Symptom Management and Survivorship Handbook (SMSH) alone and 93 received Telephone Interpersonal Counseling (TIPC) + SMSH.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High Need A; Start With SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | 24.53 score on a scale | Standard Error 0.68 |
| High Need B: Start With SMSH+TIPC | Symptom Severity Index- Comparison of Two Groups Created by First Randomization | 25.86 score on a scale | Standard Error 1.15 |
Comparison: The null hypothesis was that the means in two arms were equal, the alternative hypothesis was that the means were not equal.~We planned to randomize 224 survivors in approximately 3:1 ratio in the first randomization; power was 0.92 to detect the adjusted d=0.54 in the comparison of the SMSH and SMSH+TIPC in the first randomization. The planned number of 224 was exceeded because more survivors than planned were determined to have high need for symptom management.p-value: 0.3195% CI: [-3.9, 1.25]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) allowing for a quick assessment of 18 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 indicated severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 5-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, higher value reflect worse outcome (greater symptom severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable.
Time frame: Weeks 5-13
Population: Non-responders to the SMSH alone after 4 weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High Need A; Start With SMSH Alone | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | 35.94 score on a scale | Standard Error 2.38 |
| High Need B: Start With SMSH+TIPC | Symptom Severity Index- Comparison of Two Groups Created by Second Randomization | 38.11 score on a scale | Standard Error 2.49 |
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 required sample size was 60 per group for .80 power or greater in two-tailed tests at the 0.05 level of significance using the effect size of Cohen's d=0.54 (adjusted for baseline and repeated measures). The actual sample size was smaller (61 total) due to the higher than planned rate of response to the SMSH alone by week 4.p-value: 0.5295% CI: [-8.91, 4.55]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
Population: Of the 375 high-need survivors initially randomized, 282 started with the Symptom Management and Survivorship Handbook (SMSH) alone and 93 received Telephone Interpersonal Counseling (TIPC) + SMSH.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High Need A; Start With SMSH Alone | Depressive Symptoms- Comparison of Two Groups Created by First Randomization. | 11.89 score on a scale | Standard Error 0.55 |
| High Need B: Start With SMSH+TIPC | Depressive Symptoms- Comparison of Two Groups Created by First Randomization. | 12.30 score on a scale | Standard Error 0.99 |
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: 0.7195% CI: [-2.63, 1.81]Regression, Linear
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
Population: Non-responders to the SMSH alone after 4 weeks randomized for the second time (N=61).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| High Need A; Start With SMSH Alone | Depressive Symptoms - Comparison of Two Groups Created by Second Randomization | 16.05 score on a scale | Standard Error 1.93 |
| High Need B: Start With SMSH+TIPC | Depressive Symptoms - Comparison of Two Groups Created by Second Randomization | 16.81 score on a scale | Standard Error 2.11 |
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: 0.7995% CI: [-6.53, 5.01]Regression, Linear