The Patient-Reported Outcomes Project of HCV-TARGET

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Patient-Reported Outcomes Project of HCV-TARGET (PROP UP)

Conditions
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Hepatitis C, Chronic, Liver Diseases

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to up to 24 weeks of HCV Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. PROMIS Fatigue-7 mean change score range = +/- 53.9 PROMIS Sleep Disturbance-8a mean change score range = +/- 47.1 PROMIS Nausea/Vomiting-4 mean change score range = +/- 44.0 PROMIS Diarrhea-6 mean change score range = +/- 42.8 PROMIS Anger-5 mean change score range = +/- 50.5. PROMIS Anxiety-4 mean change score range = +/- 41.4 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. | Baseline to up to 24 weeks of HCV Treatment | 
| 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. | Baseline to up to 24 weeks of HCV Treatment | 
| 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. | Up to 24 weeks of HCV Treatment | 
| 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). | Up to 24 weeks of HCV Treatment | 
| 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. | Baseline to 3-months post-treatment | 
| 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 PROMIS Fatigue mean change score range = +/- 53.9 PROMIS Sleep Disturbance mean change score range = +/- 47.1 PROMIS Nausea mean change score range = +/- 44.0 PROMIS Diarrhea mean change score range = +/- 42.8 PROMIS Anger mean change score range = +/- 50.5. PROMIS Anxiety mean change score range = +/- 41.4 PROMIS Depression mean change score range = +/- 43.1 PROMIS Cognitive Concern mean change score range = +/- 39.5 PROMIS Pain mean change score range = +/- 36.4 PROMIS Belly Pain mean change score range = +/- 50.2 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 | Baseline to 3-months post-treatment | 
| 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. | Baseline to 3-months post-treatment | 
| 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 | Baseline to 1 year post-treatment | 
| 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 PROMIS Fatigue mean change score range = +/- 53.9 PROMIS Sleep Disturbance mean change score range = +/- 47.1 PROMIS Nausea mean change score range = +/- 44.0 PROMIS Diarrhea mean change score range = +/- 42.8 PROMIS Anger mean change score range = +/- 50.5. PROMIS Anxiety mean change score range = +/- 41.4 PROMIS Depression mean change score range = +/- 43.1 PROMIS Cognitive Concern mean change score range = +/- 39.5 PROMIS Pain mean change score range = +/- 36.4 PROMIS Belly Pain mean change score range = +/- 50.2 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 | Baseline to 1 year post-treatment | 
| 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. | Baseline to 1 year post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patient-reported outcomes, observational, HCV, Liver Disease, Liver, Infectious Disease, Hepatitis C, PROs