Hepatitis C, Chronic, Liver Diseases
Conditions
Keywords
patient-reported outcomes, observational, HCV, Hepatitis C, Liver Disease, Liver, Infectious Disease, PROs
Brief summary
The PROP UP research study is funded by The Patient Centered Outcomes Research Institute (PCORI). PROP UP is a multi-centered prospective observational study that will evaluate all-oral treatment regimens for chronic hepatitis C viral (HCV) infection regarding several patient-reported outcomes (PROs) such as HCV-associated symptoms, treatment side effects, medication adherence, out of pocket costs, comorbid conditions, and long-term benefits of cure and harms of treatment to compare PROs of different treatment regimens, treatment durations, and patient subgroups. Participants will be recruited from 9 U.S. liver centers. Approximately 1920 patients with HCV infection who are prescribed a regimen containing Sofosbuvir/Ledipasvir(SOF/LED), SOF/Velpatasvir(SOF/VEL), Grazoprevir/Elbasvir(GRZ/ELB), OBV/PTV/r + DSV (PRoD), or daclatasvir/SOF (DAC/SOF) will be recruited and approximately 1600 patients who are approved and begin HCV treatment will be enrolled in the longitudinal study. PRO surveys will be evaluated before, during and after HCV treatment. PROP UP is a collaborative effort between behavioral and biomedical researchers, a patient engagement group and a patient advocacy organization.
Detailed description
Newer, more effective all-oral regimens for hepatitis C viral (HCV) infection are available. However the available data from industry-sponsored trials do not provide all the information that patients need, nor do these data represent the broad spectrum of patients treated in real-world practice. Trials also exclude disadvantaged subgroups, focus on short-term efficacy and clinician-rated adverse events, rarely obtain the patient's perspective, and do not investigate longer-term harms of treatment or benefits of viral cure. Given these informational gaps, patient-centered outcomes research on treatment harms and benefits that matter most to patients, is needed. PROP UP is funded by The Patient Centered Outcomes Research Institute (PCORI). PROP UP is a multi-centered prospective observational study that will evaluate newly approved direct acting antiviral (DAA) treatment regimens for HCV regarding several patient-reported outcomes (PROs) such as HCV-associated symptoms, treatment side effects, medication adherence, out of pocket costs, comorbid conditions, and long-term benefits of cure and harms of treatment to compare PROs of different treatment regimens, treatment durations, and patient subgroups. PROP UP is a collaborative effort between researchers, a patient engagement group, and a patient advocacy organization. Eleven U.S. liver centers will collaborate on PROP UP. Approximately 1920 patients with HCV infection who are prescribed a DAA regimen for chronic HCV will be consented and will complete baseline PRO surveys. Approximately 1600 patients who are approved and begin HCV treatment will be enrolled in the longitudinal study. Participants will complete several PRO surveys at 5 assessment periods during the study: baseline, treatment week 4, end of treatment, 3 months post-treatment, and 12 months post-treatment. PRO survey data will be collected via 3 options: patient home-based computers, tablet, smartphone; phone-administered surveys with a centralized call enter; or at regular clinic visits. Analysis of PROs collected longitudinally before, during and after treatment for HCV will allow the investigators to answer a variety of questions important to patients and clinicians. Specifically, the investigators will evaluate: (a) prevalence of pre-existing baseline symptoms associated with HCV; (b) the development of new onset treatment side effects and exacerbation of pre-existing symptoms during HCV treatment; (c) medication adherence and out of pocket costs associated with treatment; (d) changes in HCV-associated symptoms and functional status in patients who are cured; (e) long-term patient-reported harms associated with treatments and long-term benefits associated with viral cure.
Interventions
None listed
Sponsors
Patient-Centered Outcomes Research Institute
University of North Carolina, Chapel Hill
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with HCV genotype 1-6 * English-speaking * Age 21 or older * Medically cleared and being prescribed one of the following DAA regimens: * sofosbuvir/ledipasvir (SOF/LED) with or without ribavirin * ombitasvir/paritaprevir/ritonavir with dasabuvir (PRoD), with or without ribavirin * elbasvir/grazoprevir (ELB/GRZ) with or without ribavirin * daclatasvir/sofosbuvir, with or without ribavirin (DAC/SOF) * sofosbuvir/velpatasvir (SOF/VEL)
Exclusion criteria
* Inability to provide written informed consent * Currently participating in a pharmaceutical-sponsored drug trial of hepatitis C treatment * Major cognitive or mental impairment * Unable to read or speak English * Unwilling or unable to complete survey questionnaires
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Total Memorial Symptom Assessment Scale Mean Score (TMSAS) From Baseline to On-Treatment | Baseline to up to 24 weeks of HCV Treatment | Change in Overall Symptom Burden was measured using the Memorial Symptom Assessment Scale (MSAS). Patients indicate the presence or absence of a symptom, and if present, rate the symptom on severity, frequency and interference. The total MSAS score (TMSAS) can range from 0 (no symptom) to 4 (symptom present and worst severity, frequency and distress). Change in TMSAS score is calculated as Baseline TMSAS mean score minus T2 TMSAS mean score or Baseline TMSAS mean score minus T3 TMSAS mean score. Change scores could range from +/- 4.0. Higher scores (+) indicate worse symptom burden. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in the TMSAS = 0.3 points; therefore TMSAS change scores \> +/- 0.3 were considered clinically meaningful. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HCV-PRO Mean Scores From Baseline to On-Treatment | Baseline to up to 24 weeks of HCV Treatment | HCV-specific Functional Well-Being was measured using the disease-specific HCV-PRO. The scale includes 16 items that measure physical, emotional and social functioning, productivity, intimacy, and perception of quality of life. The Means provided are the HCV-PRO Mean Change Scores, calculated as Baseline HCV-PRO mean score minus T2 HCV-PRO mean score or Baseline HCV-PRO mean score minus T3 HCV-PRO mean score. HCV-PRO mean change scores range from +/- 100. Higher change scores (+) indicate better HCV-PRO outcomes. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in HCV-PRO = 4 points; therefore HCV-PRO change scores \> +/- 4.0 were considered clinically meaningful. |
| Cumulative Out of Pocket Costs During HCV Treatment | Up to 24 weeks of HCV Treatment | Cumulative out of pocket (OOP) costs incurred by patients during HCV treatment was measured by a survey recording 5 direct and 5 indirect costs of treatment. OOP costs were collected early on-treatment (T2), late on-treatment (T3), and early post-treatment (T4) in case patients paid bills after treatment ended. The Mean is the average dollar ($$) amount for Total OOP Cost of HCV Treatment for the cohort, calculated by summing the OOP costs for each patient reported at T2+T3+T4. |
| Percentage of Participants With Nonadherence During HCV Treatment | Up to 24 weeks of HCV Treatment | Medication adherence was measured using the Voils' Medication Adherence Survey (VMAS). The VMAS consists of 3 items that evaluated the extent of adherence using a 5-point Likert scale from 1=None of the time to 5=All of the time. The 3 items assess how often participants missed doses, skip doses, or do not take doses over the past 7 days and are averaged into a single score. A dichotomous variable was created to categorize patients as 100% (adherent) or \<100% (nonadherent) during HCV treatment at early treatment (T2) and late treatment (T3). |
| Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 3-months Post Treatment | Baseline to 3-months post-treatment | Change in Overall Symptom Burden from Baseline to 3-months post-treatment was measured using the Memorial Symptom Assessment Scale (MSAS). The total Overall Symptom Burden mean change score (TMSAS) was calculated as Baseline TMSAS mean score minus T4 TMSAS mean score. Lower scores (-) indicate better outcomes. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. TMSAS Mean Change Scores could range from +/- 4. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in the TMSAS = 0.3 points; therefore TMSAS change scores \> +/- 0.3 were considered clinically meaningful. |
| Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Baseline to up to 24 weeks of HCV Treatment | Change in Treatment-Related Symptoms was measured using multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) and the Headache Impact Test (HIT-6). Mean CHANGE Scores were calculated as baseline mean score minus T2 mean score or baseline mean score minus T3 mean score. Lower change scores (-) indicate symptoms improved. 1. PROMIS Fatigue-7 mean change score range = +/- 53.9 2. PROMIS Sleep Disturbance-8a mean change score range = +/- 47.1 3. PROMIS Nausea/Vomiting-4 mean change score range = +/- 44.0 4. PROMIS Diarrhea-6 mean change score range = +/- 42.8 5. PROMIS Anger-5 mean change score range = +/- 50.5. 6. PROMIS Anxiety-4 mean change score range = +/- 41.4 7. HIT-6 mean change score range = +/- 42 To aid in interpretation of clinical significance, a 5% change from baseline is considered a minimally important change (MIC). The 5% MIC change in a PROMIS or HIT-6 score is +/- 2.5 points. |
| Change in HCV-PRO Mean Score From Baseline to 3-months Post Treatment | Baseline to 3-months post-treatment | HCV-specific Functional Well-Being was measured using the disease-specific HCV-PRO. The means provided are the HCV-PRO Mean Change Scores, calculated as Baseline HCV-PRO mean score minus T4 HCV-PRO mean score. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. HCV-PRO Mean Change Scores could range from +/- 100. Higher change scores (+) indicate better HCV-PRO outcomes. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in HCV-PRO = 4 points; therefore HCV-PRO change scores \> +/- 4.0 were considered clinically meaningful. |
| Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 1 Year Post-Treatment | Baseline to 1 year post-treatment | Change in Overall Symptom Burden from Baseline to 1 year post-treatment was measured using the Memorial Symptom Assessment Scale (MSAS). The total Overall Symptom Burden mean change score (TMSAS) was calculated as Baseline TMSAS mean score minus T5 TMSAS mean score. Lower scores (-) indicate better outcomes. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. TMSAS Mean Change Scores could range from +/- 4. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in the TMSAS = 0.3 points; therefore TMSAS change scores \> +/- 0.3 were considered clinically meaningful |
| Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Baseline to 1 year post-treatment | Change in Symptoms was measured using surveys below. Change scores were calculated as baseline mean minus T5 mean. Lower change scores (-) indicate symptom improved 1. PROMIS Fatigue mean change score range = +/- 53.9 2. PROMIS Sleep Disturbance mean change score range = +/- 47.1 3. PROMIS Nausea mean change score range = +/- 44.0 4. PROMIS Diarrhea mean change score range = +/- 42.8 5. PROMIS Anger mean change score range = +/- 50.5. 6. PROMIS Anxiety mean change score range = +/- 41.4 7. PROMIS Depression mean change score range = +/- 43.1 8. PROMIS Cognitive Concern mean change score range = +/- 39.5 9. PROMIS Pain mean change score range = +/- 36.4 10. PROMIS Belly Pain mean change score range = +/- 50.2 11. Headache HIT-6 mean change score range = +/- 42 A 5% change from baseline is considered the clinically minimally important change (MIC). The 5% MIC = +/- 2.5 points. Change scores were calculated for two subgroups: Patients who did and did not achieve SVR |
| Change in HCV-PRO Mean Score From Baseline to 1 Year Post-treatment | Baseline to 1 year post-treatment | HCV-specific Functional Well-Being was measured using the disease-specific HCV-PRO. The scale includes 16 items that measure physical, emotional and social functioning, productivity, intimacy, and perception of quality of life. The Means provided are the HCV-PRO Mean Change Scores, calculated as Baseline HCV-PRO mean score minus T5 HCV-PRO mean score. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. HCV-PRO mean change scores could range from +/- 100. Higher change scores (+) indicate better HCV-PRO outcomes. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in HCV-PRO = 4 points; therefore HCV-PRO change scores \> +/- 4.0 were considered clinically meaningful. |
| Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Baseline to 3-months post-treatment | Change in Symptoms was measured using surveys below. Change scores were calculated as baseline mean minus T4 mean. Lower change scores (-) indicate symptom improved 1. PROMIS Fatigue mean change score range = +/- 53.9 2. PROMIS Sleep Disturbance mean change score range = +/- 47.1 3. PROMIS Nausea mean change score range = +/- 44.0 4. PROMIS Diarrhea mean change score range = +/- 42.8 5. PROMIS Anger mean change score range = +/- 50.5. 6. PROMIS Anxiety mean change score range = +/- 41.4 7. PROMIS Depression mean change score range = +/- 43.1 8. PROMIS Cognitive Concern mean change score range = +/- 39.5 9. PROMIS Pain mean change score range = +/- 36.4 10. PROMIS Belly Pain mean change score range = +/- 50.2 11. Headache HIT-6 mean change score range = +/- 42 A 5% change from baseline is considered the clinically minimally important change (MIC). The 5% MIC = +/- 2.5 points. Change scores were calculated for two subgroups: Patients who did and did not achieve SVR |
Countries
United States
Participant flow
Recruitment details
11 liver or gastroenterology centers in the United States: 9 academic medical centers, 2 private gastroenterology centers. 1601 patients officially enrolled who provided informed consent, completed baseline patient-reported outcome (PRO) surveys and were prescribed one of five direct acting antiviral treatment regimens for chronic hepatitis C.
Pre-assignment details
None. Observational study included enrolled patients who completed PRO data at follow-up time periods.
Participants by arm
| Arm | Count |
|---|---|
| Chronic HCV Patients on Treatment All 1,601 patients with chronic HCV enrolled at baseline | 1,601 |
| Total | 1,601 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 12 Weeks Post-Treatment (T4) | Missing T4 record | 3 |
| 1-Yr Post-Treatment (T5) | Missing T5 Record | 88 |
| Early On-Treatment (T2) | Missing T2 Record | 51 |
| Late On-Treatment (T3) | missing T3 Record | 49 |
Baseline characteristics
| Characteristic | Chronic HCV Patients on Treatment |
|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 66 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1260 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 275 Participants |
| HCV-PRO Functional Well-Being | 71.7 units on a scale STANDARD_DEVIATION 22.3 |
| Headache Impact Test (HIT-6) | 45.3 units on a scale STANDARD_DEVIATION 10 |
| PROMIS Abdominal Pain | 36.1 units on a scale STANDARD_DEVIATION 12.9 |
| PROMIS Anger | 48.9 units on a scale STANDARD_DEVIATION 11.2 |
| PROMIS Anxiety | 50.4 units on a scale STANDARD_DEVIATION 10.2 |
| PROMIS Cognitive Concerns | 33 units on a scale STANDARD_DEVIATION 9 |
| PROMIS Depression | 49.3 units on a scale STANDARD_DEVIATION 10.5 |
| PROMIS Diarrhea | 35.6 units on a scale STANDARD_DEVIATION 8.7 |
| PROMIS Fatigue | 51.8 units on a scale STANDARD_DEVIATION 10.8 |
| PROMIS Nausea and Vomiting | 41.6 units on a scale STANDARD_DEVIATION 8.5 |
| PROMIS Pain Interference | 53 units on a scale STANDARD_DEVIATION 11 |
| PROMIS Sleep Disturbance | 51.8 units on a scale STANDARD_DEVIATION 11.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 17 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 519 Participants |
| Race (NIH/OMB) More than one race | 32 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 47 Participants |
| Race (NIH/OMB) White | 975 Participants |
| Region of Enrollment United States | 1601 Participants |
| Sex: Female, Male Female | 714 Participants |
| Sex: Female, Male Male | 887 Participants |
| TMSAS Overall Symptom Burden | 0.6 units on a scale STANDARD_DEVIATION 0.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 34 / 1,601 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Change in the Total Memorial Symptom Assessment Scale Mean Score (TMSAS) From Baseline to On-Treatment
Change in Overall Symptom Burden was measured using the Memorial Symptom Assessment Scale (MSAS). Patients indicate the presence or absence of a symptom, and if present, rate the symptom on severity, frequency and interference. The total MSAS score (TMSAS) can range from 0 (no symptom) to 4 (symptom present and worst severity, frequency and distress). Change in TMSAS score is calculated as Baseline TMSAS mean score minus T2 TMSAS mean score or Baseline TMSAS mean score minus T3 TMSAS mean score. Change scores could range from +/- 4.0. Higher scores (+) indicate worse symptom burden. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in the TMSAS = 0.3 points; therefore TMSAS change scores \> +/- 0.3 were considered clinically meaningful.
Time frame: Baseline to up to 24 weeks of HCV Treatment
Population: Of 1533 patients with complete record at T2, 1517 provided sufficient TMSAS data to calculate change score.~Of 1524 patients with complete record at T3, 1513 provided sufficient TMSAS data to calculate change score.~Discrepancies due to missing TMSAS data at T2 or T3.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chronic HCV Patients on Therapy | Change in the Total Memorial Symptom Assessment Scale Mean Score (TMSAS) From Baseline to On-Treatment | Change in TMSAS score from T1 to T3 | -0.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in the Total Memorial Symptom Assessment Scale Mean Score (TMSAS) From Baseline to On-Treatment | Change in TMSAS score from T1 to T2 | -0.10 units on a scale |
Secondary
Change in HCV-PRO Mean Score From Baseline to 1 Year Post-treatment
HCV-specific Functional Well-Being was measured using the disease-specific HCV-PRO. The scale includes 16 items that measure physical, emotional and social functioning, productivity, intimacy, and perception of quality of life. The Means provided are the HCV-PRO Mean Change Scores, calculated as Baseline HCV-PRO mean score minus T5 HCV-PRO mean score. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. HCV-PRO mean change scores could range from +/- 100. Higher change scores (+) indicate better HCV-PRO outcomes. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in HCV-PRO = 4 points; therefore HCV-PRO change scores \> +/- 4.0 were considered clinically meaningful.
Time frame: Baseline to 1 year post-treatment
Population: 1430 of 1601 patients had post-treatment HCV RNA available to determine SVR status: 1362 achieved SVR, 68 did not. SVR data were missing on 171 patients. Of 1430, T5 records were missing for 93 cases (1337 remaining). Of the remaining 1337 records, HCV-PRO data were missing for 156 patients (1181 remaining: 1132 with SVR, 49 with no SVR)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronic HCV Patients on Therapy | Change in HCV-PRO Mean Score From Baseline to 1 Year Post-treatment | 7.0 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV-PRO Mean Score From Baseline to 1 Year Post-treatment | 0.6 units on a scale |
Secondary
Change in HCV-PRO Mean Score From Baseline to 3-months Post Treatment
HCV-specific Functional Well-Being was measured using the disease-specific HCV-PRO. The means provided are the HCV-PRO Mean Change Scores, calculated as Baseline HCV-PRO mean score minus T4 HCV-PRO mean score. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. HCV-PRO Mean Change Scores could range from +/- 100. Higher change scores (+) indicate better HCV-PRO outcomes. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in HCV-PRO = 4 points; therefore HCV-PRO change scores \> +/- 4.0 were considered clinically meaningful.
Time frame: Baseline to 3-months post-treatment
Population: Of 1601 patients enrolled, 1430 patients had post-treatment HCV RNA available to determine SVR status. Of these, 1362 achieved SVR, 68 did not achieve SVR. SVR data were missing on 171 patients. Additional missing numbers due to missing HCV-PRO survey data at 3-months post-treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronic HCV Patients on Therapy | Change in HCV-PRO Mean Score From Baseline to 3-months Post Treatment | 6.5 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV-PRO Mean Score From Baseline to 3-months Post Treatment | 2.0 units on a scale |
Secondary
Change in HCV-PRO Mean Scores From Baseline to On-Treatment
HCV-specific Functional Well-Being was measured using the disease-specific HCV-PRO. The scale includes 16 items that measure physical, emotional and social functioning, productivity, intimacy, and perception of quality of life. The Means provided are the HCV-PRO Mean Change Scores, calculated as Baseline HCV-PRO mean score minus T2 HCV-PRO mean score or Baseline HCV-PRO mean score minus T3 HCV-PRO mean score. HCV-PRO mean change scores range from +/- 100. Higher change scores (+) indicate better HCV-PRO outcomes. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in HCV-PRO = 4 points; therefore HCV-PRO change scores \> +/- 4.0 were considered clinically meaningful.
Time frame: Baseline to up to 24 weeks of HCV Treatment
Population: Of 1533 patients with data records at T2, 1346 had analyzable HCV-PRO data at T2.~Of 1524 patients with data records at T3, 1356 had analyzable HCV-PRO data at T3. Discrepancies due to missing HCV-PRO data.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chronic HCV Patients on Therapy | Change in HCV-PRO Mean Scores From Baseline to On-Treatment | Change in HCV-PRO mean score from T1 to T2 | 3.2 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV-PRO Mean Scores From Baseline to On-Treatment | Change in HCV-PRO mean score from T1 to T3 | 3.8 units on a scale |
Secondary
Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment
Change in Symptoms was measured using surveys below. Change scores were calculated as baseline mean minus T4 mean. Lower change scores (-) indicate symptom improved 1. PROMIS Fatigue mean change score range = +/- 53.9 2. PROMIS Sleep Disturbance mean change score range = +/- 47.1 3. PROMIS Nausea mean change score range = +/- 44.0 4. PROMIS Diarrhea mean change score range = +/- 42.8 5. PROMIS Anger mean change score range = +/- 50.5. 6. PROMIS Anxiety mean change score range = +/- 41.4 7. PROMIS Depression mean change score range = +/- 43.1 8. PROMIS Cognitive Concern mean change score range = +/- 39.5 9. PROMIS Pain mean change score range = +/- 36.4 10. PROMIS Belly Pain mean change score range = +/- 50.2 11. Headache HIT-6 mean change score range = +/- 42 A 5% change from baseline is considered the clinically minimally important change (MIC). The 5% MIC = +/- 2.5 points. Change scores were calculated for two subgroups: Patients who did and did not achieve SVR
Time frame: Baseline to 3-months post-treatment
Population: Of 1601 patients enrolled, 1430 patients had post-treatment HCV RNA available to determine SVR status. Of these, 1362 achieved SVR, 68 did not achieve SVR. SVR data were missing on 171 patients. Missing numbers below are due to missing PRO survey data at T4.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Cognitive Concerns change score | -1.4 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Sleep change score | -3.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Anxiety change score | -1.7 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Belly Pain change score | -2.3 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Pain Interference change score | -2.3 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Diarrhea change score | -0.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Anger change score | -2.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Nausea change score | -1.5 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Fatigue change score | -4.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Headache change score | -1.5 units on a scale |
| Chronic HCV Patients on Therapy | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Depression change score | -2.3 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Headache change score | -1.1 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Depression change score | 0.2 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Anger change score | 0.7 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Anxiety change score | -0.7 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Cognitive Concerns change score | 0 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Pain Interference change score | -1.7 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Fatigue change score | -2.9 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Sleep change score | -0.9 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Belly Pain change score | 0.9 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Diarrhea change score | 0.7 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in HCV Symptom Mean Scores From Baseline to 3-months Post Treatment | Nausea change score | -0.3 units on a scale |
Secondary
Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 1 Year Post-Treatment
Change in Overall Symptom Burden from Baseline to 1 year post-treatment was measured using the Memorial Symptom Assessment Scale (MSAS). The total Overall Symptom Burden mean change score (TMSAS) was calculated as Baseline TMSAS mean score minus T5 TMSAS mean score. Lower scores (-) indicate better outcomes. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. TMSAS Mean Change Scores could range from +/- 4. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in the TMSAS = 0.3 points; therefore TMSAS change scores \> +/- 0.3 were considered clinically meaningful
Time frame: Baseline to 1 year post-treatment
Population: 1430 of 1601 patients had post-treatment HCV RNA available to determine SVR status: 1362 achieved SVR, 68 did not. SVR data were missing on 171 patients. Of 1430, T5 records were missing for 93 cases (1337 remaining). Of the remaining 1337 records, TMSAS data were missing for 17 patients (1320 remaining: 1269 with SVR, 51 with no SVR)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronic HCV Patients on Therapy | Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 1 Year Post-Treatment | -0.2 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 1 Year Post-Treatment | 0 units on a scale |
Secondary
Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 3-months Post Treatment
Change in Overall Symptom Burden from Baseline to 3-months post-treatment was measured using the Memorial Symptom Assessment Scale (MSAS). The total Overall Symptom Burden mean change score (TMSAS) was calculated as Baseline TMSAS mean score minus T4 TMSAS mean score. Lower scores (-) indicate better outcomes. Change scores were calculated for two subgroups: (1) Patients who achieved SVR and (2) patients who did not achieve SVR. TMSAS Mean Change Scores could range from +/- 4. To aid in interpretation of clinically significant change, a \>5% change from baseline was set as the minimally important change (MIC) threshold. A 5% change in the TMSAS = 0.3 points; therefore TMSAS change scores \> +/- 0.3 were considered clinically meaningful.
Time frame: Baseline to 3-months post-treatment
Population: Of 1601 patients enrolled, 1430 patients had post-treatment HCV RNA available to determine SVR status. Of these, 1362 achieved SVR, 68 did not achieve SVR. SVR data were missing on 171 patients. Additional missing numbers (from 1362 to 1313 and 68 to 58) were due to missing MSAS survey data at 3-months post-treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronic HCV Patients on Therapy | Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 3-months Post Treatment | -0.2 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Change in Total Memorial Symptom Assessment Scale (TMSAS) Mean Score From Baseline to 3-months Post Treatment | -0.1 units on a scale |
Secondary
Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment
Change in Treatment-Related Symptoms was measured using multiple surveys from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) and the Headache Impact Test (HIT-6). Mean CHANGE Scores were calculated as baseline mean score minus T2 mean score or baseline mean score minus T3 mean score. Lower change scores (-) indicate symptoms improved. 1. PROMIS Fatigue-7 mean change score range = +/- 53.9 2. PROMIS Sleep Disturbance-8a mean change score range = +/- 47.1 3. PROMIS Nausea/Vomiting-4 mean change score range = +/- 44.0 4. PROMIS Diarrhea-6 mean change score range = +/- 42.8 5. PROMIS Anger-5 mean change score range = +/- 50.5. 6. PROMIS Anxiety-4 mean change score range = +/- 41.4 7. HIT-6 mean change score range = +/- 42 To aid in interpretation of clinical significance, a 5% change from baseline is considered a minimally important change (MIC). The 5% MIC change in a PROMIS or HIT-6 score is +/- 2.5 points.
Time frame: Baseline to up to 24 weeks of HCV Treatment
Population: Sample size may differ for each mean change score due to missing survey data.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Diarrhea mean score from T1 to T2 | 0.8 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in sleep disturbance score from T1 to T3 | -1.8 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in headache HIT-6 mean score from T1 to T3 | -0.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Fatigue Mean Score from T1 to T2 | -1.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Sleep disturbance score from T1 to T2 | -1.6 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Nausea/Vomiting mean score from T1 to T2 | 0.8 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Irritability mean score from T1 to T2 | -1.2 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Anxiety mean score from T1 to T2 | -1.5 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in headache HIT-6 mean score from T1 to T2 | 0.2 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Fatigue mean score from T1 to T3 | -1.1 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in nausea/vomiting mean score from T1 to T3 | -0.2 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in Diarrhea mean score from T1 to T3 | 0.6 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in anger mean score from T1 to T3 | -0.8 units on a scale |
| Chronic HCV Patients on Therapy | Change in Treatment-Related Symptom Mean Scores From Baseline to On-Treatment | Change in anxiety mean score from T1 to T3 | -1.4 units on a scale |
Secondary
Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment
Change in Symptoms was measured using surveys below. Change scores were calculated as baseline mean minus T5 mean. Lower change scores (-) indicate symptom improved 1. PROMIS Fatigue mean change score range = +/- 53.9 2. PROMIS Sleep Disturbance mean change score range = +/- 47.1 3. PROMIS Nausea mean change score range = +/- 44.0 4. PROMIS Diarrhea mean change score range = +/- 42.8 5. PROMIS Anger mean change score range = +/- 50.5. 6. PROMIS Anxiety mean change score range = +/- 41.4 7. PROMIS Depression mean change score range = +/- 43.1 8. PROMIS Cognitive Concern mean change score range = +/- 39.5 9. PROMIS Pain mean change score range = +/- 36.4 10. PROMIS Belly Pain mean change score range = +/- 50.2 11. Headache HIT-6 mean change score range = +/- 42 A 5% change from baseline is considered the clinically minimally important change (MIC). The 5% MIC = +/- 2.5 points. Change scores were calculated for two subgroups: Patients who did and did not achieve SVR
Time frame: Baseline to 1 year post-treatment
Population: 1430 patients had post-treatment HCV RNA available to determine SVR status: 1362 achieved SVR, 68 did not. SVR data were missing on 171 patients. T5 records were missing for 93 cases. Discrepancies from 1362 and 68 due to missing survey data at T5 for specific measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Cognitive Concern change score | -1.7 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Sleep Disturbance change score | -3.1 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Anxiety change score | -2.0 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Belly Pain change score | -2.6 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Pain Interference change score | -1.9 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Diarrhea change score | -0.3 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Anger change score | -2.2 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Nausea change score | -1.4 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Fatigue change score | -3.6 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Headache HIT-6 Change score | -1.5 units on a scale |
| Chronic HCV Patients on Therapy | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Depression change score | -2.2 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Headache HIT-6 Change score | -0.7 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Depression change score | -0.9 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Anger change score | -0.3 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Anxiety change score | -0.4 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Cognitive Concern change score | 0.3 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Pain Interference change score | -0.8 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Fatigue change score | -0.6 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Sleep Disturbance change score | -1.3 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Belly Pain change score | -3.7 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Diarrhea change score | -0.1 units on a scale |
| Patients Without Baseline Mental Health Disturbance | Changes in HCV Symptom Mean Scores From Baseline to 1 Year Post-Treatment | Nausea change score | -0.1 units on a scale |
Secondary
Cumulative Out of Pocket Costs During HCV Treatment
Cumulative out of pocket (OOP) costs incurred by patients during HCV treatment was measured by a survey recording 5 direct and 5 indirect costs of treatment. OOP costs were collected early on-treatment (T2), late on-treatment (T3), and early post-treatment (T4) in case patients paid bills after treatment ended. The Mean is the average dollar ($$) amount for Total OOP Cost of HCV Treatment for the cohort, calculated by summing the OOP costs for each patient reported at T2+T3+T4.
Time frame: Up to 24 weeks of HCV Treatment
Population: Of 1601 patients enrolled, OOP cost data was recorded by 1578 patients. Due to unreliable data, especially at the upper limit, 40 cases (2.53%) were eliminated from each tail (lower and upper limit), totaling 80 cases (5.06%) of the 1578 sample. OOP dollar amount below based on 1498 cases.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Chronic HCV Patients on Therapy | Cumulative Out of Pocket Costs During HCV Treatment | 582.50 units on a scale |
Secondary
Percentage of Participants With Nonadherence During HCV Treatment
Medication adherence was measured using the Voils' Medication Adherence Survey (VMAS). The VMAS consists of 3 items that evaluated the extent of adherence using a 5-point Likert scale from 1=None of the time to 5=All of the time. The 3 items assess how often participants missed doses, skip doses, or do not take doses over the past 7 days and are averaged into a single score. A dichotomous variable was created to categorize patients as 100% (adherent) or \<100% (nonadherent) during HCV treatment at early treatment (T2) and late treatment (T3).
Time frame: Up to 24 weeks of HCV Treatment
Population: Of 1601 enrolled patients, 1562 had VMAS adherence data at either early treatment (T2) or late treatment (T3). 1513 patients had adherence data at T2. 1476 patients had adherence data at T3.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chronic HCV Patients on Therapy | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) early on-treatment (T2) | 4.5 percentage of participants |
| Chronic HCV Patients on Therapy | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) late on-treatment (T3) | 9 percentage of participants |
| Patients Without Baseline Mental Health Disturbance | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) early on-treatment (T2) | 4.2 percentage of participants |
| Patients Without Baseline Mental Health Disturbance | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) late on-treatment (T3) | 7.6 percentage of participants |
| Patients With Baseline Alcohol Abuse | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) early on-treatment (T2) | 5.9 percentage of participants |
| Patients With Baseline Alcohol Abuse | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) late on-treatment (T3) | 13.7 percentage of participants |
| Patients Without Baseline Alcohol Abuse | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) early on-treatment (T2) | 4 percentage of participants |
| Patients Without Baseline Alcohol Abuse | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) late on-treatment (T3) | 7.2 percentage of participants |
| Patients With Baseline Substance Use | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) early on-treatment (T2) | 5.5 percentage of participants |
| Patients With Baseline Substance Use | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) late on-treatment (T3) | 9 percentage of participants |
| Patients Without Baseline Substance Use | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) early on-treatment (T2) | 4.3 percentage of participants |
| Patients Without Baseline Substance Use | Percentage of Participants With Nonadherence During HCV Treatment | Nonadherence rate (%) late on-treatment (T3) | 7.8 percentage of participants |