Patient-Reported Outcome Assessments as Endpoints in Studies in Infectious Diseases

Powers, John H.; Howard, Kellee; Saretsky, T.; Clifford, Sarah; Hoffmann, Steve; Llorens, Lily; Talbot, George H.

doi:10.1093/cid/ciw317

Cited by 38 publications

(33 citation statements)

References 40 publications

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“…Standardization of methods for capturing symptoms improves the accuracy and efficiency of clinical trials. 38 The evidence in this study, consistent with FDA guidance, 11 supports the future use of the FLU-PRO in trials for RSV disease prevention. Given the clinical similarity among symptoms of respiratory illnesses in older adults, the FLU-PRO could also be used in studies of other respiratory viral illnesses.…”

Section: Limitationssupporting

confidence: 76%

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation

Powers

Vallo

et al. 2020

Value in Health

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Objectives: There are no approved vaccines for respiratory syncytial virus (RSV), and consensus on methods to assess RSV vaccine efficacy has not been established. In this study of an adjuvanted RSV vaccine, we evaluated an RSV disease endpoint using a patient-reported outcome instrument (the inFLUenza Patient-Reported Outcome instrument [FLU-PRO]) and molecular testing for virologic confirmation. Methods: In a randomized, blinded efficacy study (NCT02508194), 1900 adult participants aged $60 years who had any respiratory symptom lasting $24 hours recorded symptoms in a FLU-PRO-based workbook for 21 days, self-collected nasal swabs on illness days 2 to 4, and had a site-collected swab obtained on (approximately) day 4. The endpoint, acute RSVassociated respiratory illness (ARA-RI), required specific symptoms with virologic confirmation. Results: The FLU-PRO demonstrated reliability, ability to detect change, and validity and had high participant adherence and acceptable patient burden in the setting of an RSV prevention trial. The ARA-RI endpoint definition captured all 33 virologically confirmed RSV illnesses for which symptom data were provided, and in 32 of these, at least 1 lower respiratory symptom was reported. Sensitivity analysis with an endpoint requiring $2 lower respiratory symptoms captured greater symptom severity but fewer cases. Results of self-and site-collected swabs were highly correlated. Selfswabbing detected 9 additional cases that would have been missed by site swabbing only. Conclusions: These results demonstrated the reliability and validity of the ARA-RI definition and of the FLU-PRO for use in RSV studies. Self-swabbing improved RSV detection.

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Section: Limitationssupporting

confidence: 76%

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation

Powers

Vallo

et al. 2020

Value in Health

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“…The TSQM 1.4 is a 14-item instrument that evaluates four domains relating to treatment satisfaction: (1) effectiveness (questions 1-3), that is, condition prevention or treatments, symptom relief; (2) side effects (questions 4-8), that is, interference with physical and mental functioning, mood, or emotions; (3) convenience (questions 9-11), that is, ease of medication use and planning, frequency of medicine use; and (4) overall satisfaction (questions [12][13][14]. For each domain, a total score of 0 to 100 was calculated according to the direction of the instrument's authors (17,18).…”

Section: Methodsmentioning

confidence: 99%

Treatment Satisfaction and Quality of Life among Type 2 Diabetes Patients: A Cross-Sectional Study in West Bank, Palestine

Khdour

Awadallah

Al-Hamed³

2020

Journal of Diabetes Research

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Objectives. This study had the goal of evaluating the role of treatment satisfaction among diabetic patients in the context of health-related quality of life (QoL) and medication adherence. Methods. This study, which utilized a cross-sectional design, was conducted at the Primary Healthcare Unit in the Ministry of Health in Ramallah between Feb. and May 2019. Medication adherence was evaluated with the 4-item Morisky Green-Levine (MGL) questionnaire, treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM 1.4), and health-related quality of life with the European Quality of Life scale (EQ-5D-3L). Results. Study participants consisted of 380 diabetic patients, of which 220 (57.9%) had high adherence to their medications and 160 (42.1%) had low adherence. Based on the classification of patient responses among the EQ-5D domains, pain/discomfort was the most influenced dimension, with 173 patients (36.1%) reporting problems, (36.1%). Also prominent were anxiety and depression (128 patients, 33.7%) and Mobility (115 patients, 30.3%). A significant relation was observed between QoL and treatment satisfaction (73.8 vs. 69.8; P=0.016). Treatment satisfaction also had a significant association with the anxiety domain (39.4 vs. 28.7; P=0.031). Conclusion. Participants expressed moderate satisfaction with their treatments; more satisfied patients showed greater medication adherence and had better QoL. Anxiety has been shown to be associated with reduced medication adherence and lower QoL.

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“…(nv-HABP), ventilated HABP (v-HABP), and VABP groups [6] suggest that pooling their outcomes raises methodological issues. Because a clinically meaningful endpoint of symptom improvement plus survival for nv-HABP is supported by the historical data for community-acquired bacterial pneumonia (CABP) [7], nv-HABP could be studied separately utilizing a patient-reported outcome (PRO) instrument, thereby standardizing symptom collection [8].…”

Section: Differences In Acm Among the Nonventilated Habpmentioning

confidence: 99%

Evidence-Based Study Design for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia

Talbot

Das

Cush

et al. 2019

The Journal of Infectious Diseases

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See the Editorial Commentary by Eby on pages 1515-7.) Background. The US Food and Drug Administration solicited evidence-based recommendations to improve guidance for studies of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). Methods. We analyzed 7 HABP/VABP datasets to explore novel noninferiority study endpoints and designs, focusing on alternatives to all-cause mortality (ACM). Results. ACM at day 28 differed for ventilated HABP (27.8%), VABP (18.0%), and nonventilated HABP (14.5%). A "mortality-plus" (ACM+) composite endpoint was constructed by combining ACM with patient-relevant, infection-related adverse events from the Medical Dictionary for Regulatory Activities toxic/septic shock standardized query. The ACM+ rate was 3-10 percentage points above that of ACM across the studies and treatment groups. Predictors of higher ACM/ACM+ rates included older age and elevated acute physiology and chronic health evaluation (APACHE) II score. Only patients in the nonventilated HABP group were able to report pneumonia symptom changes. Conclusions. If disease groups and patient characteristics in future studies produce an ACM rate so low (<10%-15%) that a fixed noninferiority margin of 10% cannot be justified (requiring an odds ratio analysis), an ACM+ endpoint could lower sample size. Enrichment of studies with patients with a higher severity of illness would increase ACM. Data on symptom resolution in nonventilated HABP support development of a patient-reported outcome instrument. Keywords. hospital-acquired bacterial pneumonia; ventilator-associated bacterial pneumonia; all-cause mortality; mortalityplus endpoint;. At the request of the US Food and Drug Administration (FDA), the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium established a project team to advance scientifically rigorous hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP) drug development based on a noninferiority (NI) study design [1].

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Patient-Reported Outcome Assessments as Endpoints in Studies in Infectious Diseases

Cited by 38 publications

References 40 publications

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation

Treatment Satisfaction and Quality of Life among Type 2 Diabetes Patients: A Cross-Sectional Study in West Bank, Palestine

Evidence-Based Study Design for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia

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