Donald Stull

Optimal recall periods for patient-reported outcomes: challenges and potential solutions

ABSTRACT Objectives: As the role and importance of patient-reported outcomes (PROs) increase, the validity and reliability of PRO measures come under greater scientific and regulatory scrutiny. One key issue is selecting the ‘most appropriate’ recall period for capturing PROs in clinical trials. This paper draws on survey research, health-specific literature, and results from clinical trials to summarize factors that can influence recall and provide guidance on selecting an optimal recall period. Methods: We conducted a systematic review of six databases and additional literature drawn from bibliographies of the selected articles. Results: Six major factors can influence recall; these can be classified into two broad areas: characteristics of the recalled phenomenon (recency, attributes, complexity) and context or meaning of the recalled phenomenon (salience, patient experience, mood). Results of different recall periods for three classes of PROs are presented: health behaviors, symptoms, and health-related quality of life. We present findings on the effect of alternative recall periods for three commonly used PROs. Finally, we propose a heuristic model to link the concept under investigation with an optimal recall period. Conclusions: No single recall period is best for all measures or all phenomena. The recall period must correspond to the characteristics of the phenomenon of interest and the purpose of the assessment. Recall period is an issue of internal validity. An incorrect recall period introduces measurement error that may reduce the chances of detecting a treatment effect. Researchers should consider recall period as seriously as they do other measurement properties.

Relationship of nasal congestion with sleep, mood, and productivity

ABSTRACT Objective: To explore the impact of nasal congestion alone relative to a full set of allergic rhinitis (AR) symptoms on sleep, fatigue, daytime somnolence, and work and school productivity in a 15-day prospective, naturalistic study. Research design and methods: Patients (N = 404) received a clinical exam to confirm congestion and assess its possible causes, including confirmed allergic rhinitis. They completed a battery of patient-reported outcomes (PROs) that assess the impact of nasal congestion and morning AR symptoms on patients’ reports of sleep, daytime sleepiness, fatigue, and work, school, and activity impairment. Data were analyzed using multiple regression. Each PRO was regressed separately on congestion and morning AR symptoms, controlling for patient demographics. Results: Nasal congestion has a significant ( p < 0.05), negative impact on patients’ lives. Nasal congestion alone had only a slightly smaller negative impact on sleep adequacy relative to AR symptoms more broadly (congestion: β = 0.137–0.534; AR: β = 0.123–0.642). Congestion increases the likelihood of sleep problems, fatigue, shortness of breath, headache, and daytime somnolence. Conclusions: A single congestion item by itself is a statistically and substantively significant predictor of patient-relevant outcomes. Although the sample was not randomly drawn from clinics or physician offices, the consistency and strength of the findings suggest the salience of this single symptom for patients’ experiences.

Relative strength of relationships of nasal congestion and ocular symptoms with sleep, mood and productivity.

ABSTRACT Background: Nasal congestion associated with allergic rhinitis has been shown to be the most bothersome symptom. Ocular symptoms may be troublesome to patients as well. Objective: To estimate the relative strength of relationships of nasal congestion and ocular symptoms associated with allergic rhinitis with patient-reported outcomes of sleep quality; practical problems; somnolence; impairment at work, class, activities; and mood. Methods: Patients (n = 404) presenting with symptoms of allergic rhinitis completed five patient-reported outcomes that assessed the effect of morning allergic rhinitis symptoms on patients’ reports of sleep, work and activity impairment, and mood. Multiple regression analyses were used to compare the relative strength of relationships of congestion and ocular symptoms with the patient-reported outcomes. Results: The majority of patients had both nasal congestion and ocular symptoms at baseline. A single nasal congestion item and a 3-item ocular symptom score were significantly related to the patient-reported outcomes: those with more severe congestion or ocular symptoms reported more negative scores on the patient-reported outcomes. Nasal congestion had the stronger relationship with patient-reported outcomes total scores or subscales in 14 of 20 regressions. Conclusion: Although nasal congestion is generally more strongly related to the patient-reported outcomes, ocular symptoms have a significant negative effect on patients’ lives. Study limitations include: (1) only baseline data were used because of greater severity and variability of symptoms scores; we are unable to establish causal relationships or discuss change, only correlation/covariation; (2) recruitment took place from September through November, thus different patients might have been recruited if sampling took place during the spring; (3) patients were screened for nasal congestion not for ocular symptoms, though there was high co-occurrence of each. These limitations aside, congestion and ocular symptoms are troublesome to patients and typically co-occur. Evaluating and treating these symptoms are key to managing allergic rhinitis and improving patient-reported outcomes.

Impact of estradiol-valerate/dienogest on work productivity and activities of daily living in European and Australian women with heavy menstrual bleeding.

Background The purpose of this study was to quantify the impact of estradiol-valerate/dienogest (E2V/DNG; Qlaira®/Natazia®) on work productivity and activities of daily living in European and Australian women with heavy menstrual bleeding. Methods Women aged 18–54 years with a confirmed diagnosis of heavy menstrual bleeding and no recognizable pathology were recruited across nine European countries (the Czech Republic, Finland, Germany, Hungary, The Netherlands, Poland, Sweden, UK, and Ukraine) and Australia. The women were randomized to receive either E2V/DNG (n = 149) or placebo (n = 82) for seven treatment cycles (196 days). The outcomes assessed included work productivity (ie, productivity while at work) and activities of daily living, measured on a Likert scale from 0 to 10 (with higher values denoting higher impairment levels) at baseline and at the end of the third and seventh cycles (days 84 and 196). The equivalent monetary value associated with the changes in work productivity and activities of daily living was also calculated. Results Across all the countries, greater improvements from baseline to the end of treatment were observed with E2V/DNG treatment than placebo in work productivity (46.0% versus 15.1%) and activities of daily living (55.6% versus 30.8%). In 2008, savings associated with improvements in work productivity and activities of daily living due to E2V/DNG treatment (net of placebo improvement) were estimated to be between US

Application of latent growth and growth mixture modeling to identify and characterize differential responders to treatment for COPD.

22–62 and US

Analysis of disease activity categories in chronic spontaneous/idiopathic urticaria

18–56 per month (in purchasing power parity of US

Assessing Changes in Chronic Spontaneous/Idiopathic Urticaria: Comparisons of Patient-Reported Outcomes Using Latent Growth Modeling.

), respectively. Conclusion E2V/DNG has a consistent positive impact on work productivity and activities of daily living in European and Australian women with heavy menstrual bleeding. These improvements were associated with a reduction in monetary burden of heavy menstrual bleeding compared with the placebo group, consistent with the response to treatment observed.

Identifying Differential Responders and Their Characteristics in Clinical Trials: Innovative Methods for Analyzing Longitudinal Data

OBJECTIVE To explore the utility of applying growth mixture models (GMMs) in secondary analyses of clinical trials to identify sources of variability in data reported by patients with COPD. METHODS Analyses were performed on data from two 6-month clinical trials comparing indacaterol and open-label tiotropium or blinded salmeterol and the first six months of a 12-month trial comparing indacaterol and blinded formoterol. Latent growth model (LGM) analyses were conducted to explore the response of the SGRQ Symptoms score from baseline to six months and GMM analyses were evaluated as a method to identify latent classes of differential responders. RESULTS Variability in SGRQ Symptom scores was found suggesting subsets of patients with differential response to treatment. GMM analyses found subsets of non-responders in all trials. When the responders were analyzed separately from non-responders, there were increased treatment effects (e.g., symptoms score improvement over six months for whole groups: indacaterol=8-12 units, tiotropium=7 units, salmeterol=9 units, formoterol=11 units. Responder subgroup improvement: indacaterol=9-21 units, tiotropium=7 units, salmeterol=10 units, formoterol=20 units). Responders had significantly different baseline SGRQ Symptom scores, smoking history, age, and mMRC dyspnea scores than non-responders. CONCLUSIONS Patients with COPD represent a heterogeneous population in terms of their reporting of symptoms and response to treatment. GMM analyses are able to identify sub-groups of responders and non-responders. Application of this methodology could be of value on other endpoints in COPD and in other disease areas.

Impact of Estradiol Valerate/Dienogest on Work Productivity and Activities of Daily Living in Women with Heavy Menstrual Bleeding

Measurement of disease activity guides treatment of chronic spontaneous urticaria (CSU). A weekly Urticaria Activity Score – here, the average of twice‐daily patient assessment of itch and hives scores summed over 1 week (UAS7TD) – measures severity from 0 to 42. Insufficient evidence exists on whether disease activity states, defined by categorical UAS7TD scores, correlate with other patient‐reported outcomes and treatment response.

The congestion quantifier five-item test for nasal congestion: refinement of the congestion quantifier seven-item test.

IntroductionAssessing the consequences of chronic spontaneous/idiopathic urticaria (CSU) requires the evaluation of health-related quality of life (HRQoL) associated with the severity of CSU signs and symptoms. It is important to understand how signs, symptoms, and HRQoL change over time in CSU. Evidence is lacking on how closely changes in signs and symptoms of CSU are related to changes in HRQoL. The objective of this study was to assess the correlation between changes in patient-reported outcome measures (PROMs) of signs and symptoms, dermatologic quality of life (QoL), and urticaria-specific QoL.MethodsLatent growth models (LGMs) were applied to longitudinal data from three randomized, Phase 3 clinical trials investigating the efficacy and safety of omalizumab in CSU.ResultsA near-perfect association between changes in signs and symptoms and changes in dermatologic and urticaria-specific QoLs was identified in each clinical trial when using LGMs (correlation coefficient range 0.88–0.92).ConclusionEvidence showed that changes in signs and symptoms are closely related to changes in HRQoL. However, analyses were performed on clinical trial results of an extremely effective treatment; a less effective treatment with much smaller changes over time may not show such close correlations. Results suggest that any of these PROMs may be used to understand changes in CSU.