Bhash Parasuraman

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.

Factors influencing patient decisions about the use of asthma controller medication.

BACKGROUND Patient nonadherence with asthma controller medication is pervasive and impedes successful adoption of national treatment guidelines. OBJECTIVE To survey adult patients with asthma about the factors influencing their decisions about when to use their asthma controller medications. METHODS Two hundred adults with asthma were randomly selected from a national database and were surveyed by telephone about medication use, barriers to adherence, and treatment preferences. RESULTS Adherence to daily controller medication in the group was generally well below the prescribed level despite the fact that many had relatively severe asthma and inadequately controlled symptoms. Thirty percent of the respondents indicated that they had been instructed by their physician to use their controller medication intermittently as guided by their symptoms. Most respondents expressed a desire to be more in control of their treatment and for that treatment to be more immediately effective and long-lasting but did not perceive inadequate information to be a barrier to adherence. CONCLUSION These insights into patient perception and motivation suggest the importance of developing treatment plans that allow patients some degree of control over medication use.

EGFR Mutation Testing in Patients with Advanced Non-Small Cell Lung Cancer: A Comprehensive Evaluation of Real-World Practice in an East Asian Tertiary Hospital

Introduction Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. Methods Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. Results This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. Conclusions In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.

Comparison of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol dry powder inhaler in asthma patients

BACKGROUND The adjustable-dose budesonide/formoterol dry powder inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI. OBJECTIVE We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized metered-dose inhaler versus the fixed-dose budesonide/formoterol pressurized metered-dose inhaler and the fixed-dose fluticasone propionate/salmeterol DPI. METHODS This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 microg x 2 inhalations [320/9 microg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 microg x 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 microg] twice daily to 2 inhalations [320/9 microg] once daily or 4 inhalations [640/18 microg] twice daily) for 6 months (treatment period 2). RESULTS There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P < .001) was used with adjustable-dose versus fixed-dose budesonide/formoterol. All treatments were well tolerated. CONCLUSIONS Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.

The effect of budesonide and formoterol in one pressurized metered-dose inhaler on patient-reported outcomes in adults with mild-to-moderate persistent asthma

ABSTRACT Objective: To determine the effects of budesonide and formoterol administered via one pressurized metered-dose inhaler (budesonide/formoterol pMDI) on patient-reported outcomes (PROs) and to determine the contributions of budesonide and formoterol to those effects in adults with asthma. Research design and methods: A 12-week, randomized, double-blind, double-dummy, placebo-controlled, multicenter study was conducted in 480 patients aged ≥ 12 years with mild-to-moderate persistent asthma. After a 2-week run-in period during which current asthma therapy was discontinued, patients were randomized to receive two inhalations twice daily of budesonide/formoterol pMDI 80/4.5 μg (160/9 μg), budesonide pMDI 80 μg (160 μg), formoterol via dry powder inhaler (DPI) 4.5 μg (9 μg), or placebo. Main outcome measures: Analyses included a subpopulation of 405 patients aged ≥ 18 years. PROs included the standardized Asthma Quality of Life Questionnaire (AQLQ(S)), the Medical Outcomes Study (MOS) Sleep Scale, the Patient Satisfaction with Asthma Medication (PSAM) questionnaire, and asthma control variables (recorded via electronic diaries), such as asthma symptoms, rescue medication use, and nighttime awakenings due to asthma. Patient and physician global assessments were collected at the end of the study. Results: Patients aged ≥ 18 years receiving budesonide/formoterol pMDI reported significantly greater improvements from baseline in AQLQ overall and domain scores, MOS Sleep Scale domain scores, and asthma control variables than patients receiving placebo ( p ≤ 0.033). Improvements from baseline in AQLQ(S) overall and domain scores, daily asthma symptoms scores, percentage of symptom-free days, percentage of rescue medication-free days, and percentage of asthma control days were significantly greater in patients receiving budesonide/formoterol pMDI versus formoterol DPI ( p ≤ 0.042). Patients receiving budesonide/formoterol pMDI reported significantly greater PSAM scores than did patients in all other treatment arms ( p ≤ 0.004). Study limitations may include the fact that the formoterol-alone arm used a different device and formulation than the other active arms as well as the absence of a treatment arm with budesonide and formoterol administered concomitantly in separate inhalers. In addition, these results may not be generalized to all patients with asthma, as this analysis included only patients aged ≥ 18 years. Conclusions: Patients receiving treatment with budesonide/formoterol pMDI experienced significantly greater improvements from baseline in asthma-related quality of life, quality of sleep, and asthma control and greater satisfaction with treatment than patients receiving placebo. The combination of budesonide and formoterol in one pMDI is beneficial in improving how a patient feels and functions as a result of treatment.

The safety and clinical benefit of budesonide/formoterol pressurized metered-dose inhaler versus budesonide alone in children.

Few studies have evaluated inhaled corticosteroid (ICS)/long-acting beta(2)-adrenergic agonist combination therapy in asthmatic children. This study was designed to evaluate the safety (primary) and clinical benefits (secondary) of budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide dry powder inhaler (DPI) in children with persistent asthma. This was a 26-week, multicenter, randomized, open-label U.S. study of 187 children 6-11 years of age previously receiving ICS. After 1 week of usual ICS therapy, subjects received twice-daily budesonide/formoterol pMDI 160/4.5 micrograms x 2 inhalations (320/9 micrograms; n = 124) or budesonide DPI 200 micrograms x 2 inhalations (400 micrograms [320 micrograms delivered ex-mouthpiece]; n = 63). Budesonide/formoterol and budesonide were well tolerated with a similar incidence of adverse events (AEs) (84.6% and 85.7%, respectively), most of mild or moderate intensity. Treatment-related AE incidence was low (5.4%) and similar across groups (budesonide/formoterol, 4.9%; budesonide, 6.3%). No clinically important treatment differences were observed for 12-lead electrocardiograms, hematology, serum glucose and potassium, and 24-hour urinary cortisol. Compared with budesonide, budesonide/formoterol decreased health care use (urgent care visits and interference with daily activities [child] or work [caregiver]; p < or = 0.012) and improved health-related quality of life (Pediatric Asthma Quality of Life Questionnaire [standardized] and Pediatric Asthma Caregiver Quality of Life Questionnaire overall scores; p < or = 0.006) and pulmonary function (predose forced expiratory volume in 1 second and forced expiratory flow during the middle half of exhalation; p < or = 0.007). In this 26-week study of asthmatic children (6-11 years), safety profiles were similar and clinical benefits were greater with budesonide/formoterol than with budesonide.

Budesonide Turbuhaler delivered once daily improves health-related quality of life and maintains improvements with a stepped-down dose in adults with mild to moderate asthma

BACKGROUND Budesonide inhalation powder administered via Turbuhaler (budesonide Turbuhaler, AstraZeneca LP, Wilmington, DE) is proven efficacious and safe in the treatment of mild to severe asthma. OBJECTIVE To evaluate the effect of once-daily budesonide Turbuhaler on health-related quality of life (HRQL) in adults with mild to moderate asthma. METHODS In this double-blind, parallel-group study, 309 asthmatic patients between 18 and 70 years of age were randomized to receive once-daily treatment with budesonide 200 or 400 microg or placebo for 6 weeks. Patients initially receiving 400 microg budesonide had their dose reduced to 200 microg (400/200-microg group), and patients receiving 200 microg (200/200-microg group) or placebo continued to receive their assigned doses for a 12-week maintenance phase. HRQL was evaluated using the Asthma Quality of Life Questionnaire at randomization, week 6, and week 18. RESULTS Compared with placebo, patients initially receiving 400 and 200 microg budesonide Turbuhaler demonstrated significantly greater HRQL scores at week 6 (P < or = 0.001 and P < or = 0.010, respectively) that were maintained at week 18 (P < or = 0.001). Clinically important (> or = 0.5 unit) improvement in Asthma Quality of Life Questionnaire overall at week 18 was demonstrated by 55% and 43% of patients in the 400/200-microg and 200/200-microg budesonide Turbuhaler groups, respectively. CONCLUSIONS In patients with mild to moderate asthma, once-daily budesonide Turbuhaler 200 and 400 microg demonstrates statistically significant and clinically important improvements in HRQL that can be maintained with a low dose of 200 microg.

Onset of effect of budesonide and formoterol administered via one pressurized metered-dose inhaler in patients with asthma previously treated with inhaled corticosteroids

BACKGROUND Onset of bronchodilation of budesonide/formoterol in one pressurized metered-dose inhaler (pMDI) has not been evaluated in asthma. OBJECTIVE To evaluate time to onset of clinically significant bronchodilation (> or = 15% improvement in forced expiratory volume in 1 second) and patient-perceived onset of effect (OE) in patients previously receiving inhaled corticosteroids. METHODS In two 12-week studies, patients 12 years and older with moderate to severe (study 1; n = 596) and mild to moderate (study 2; n = 480) persistent asthma received budesonide/formoterol pMDI, budesonide pMDI plus formoterol dry powder inhaler (study 1 only), budesonide pMDI, formoterol dry powder inhaler, or placebo. Postdose time to 15% or greater improvement in forced expiratory volume in 1 second and patient-perceived OE (assessed in a subset of patients 18 years and older [study 1, n=553; study 2, n=405]) were evaluated [corrected] RESULTS More budesonide/formoterol-treated patients achieved onset of clinically significant bronchodilation within 15 minutes (median, 13 minutes) of administration at randomization vs those taking budesonide or placebo (P < .001). More patients receiving budesonide/formoterol vs budesonide and placebo reported feeling their study medication begin to work right away (P < or = .004; end of week 1). Similar results (P < .001) were observed for patient satisfaction with how quickly they felt their medication begin to work (except budesonide/formoterol vs budesonide, study 1 [P = .073]). Time to onset of clinically significant bronchodilation and patient-perceived OE of budesonide/formoterol and formoterol were similar. CONCLUSION Budesonide/formoterol demonstrated a more rapid onset of clinically significant bronchodilation and a greater percentage of patients who perceived their medication working right away vs budesonide or placebo.

Development of the Asthma Treatment Satisfaction Measure

Abstract Objective: Study aims were to develop and assess the measurement properties of a four-part treatment satisfaction measure for patients with asthma. The Asthma Treatment Satisfaction Measure (ATSM) incorporates specific attributes representing patient expectations, treatment preferences, self-reported treatment outcomes, and overall treatment satisfaction. This paper describes patients’ ability to detect change in their satisfaction with asthma therapies using the ATSM. Methods: Adult patients with chronic asthma requiring a change in their asthma controller medications were recruited from sites in the US and Canada. Interviews were conducted with 22 patients to elicit areas important to patients in asthma treatment for measurement of satisfaction, providing the basis for the four-part questionnaire that was then tested for clarity. An additional 105 patients participated in the validation study and completed the first two parts of the ATSM (expectations and importance of treatment) at their initial visit (baseline) prior to a change in treatment. Parts 3 and 4 (treatment outcomes and treatment satisfaction) were completed after 4 weeks on the new treatment. A daily diary was completed by patients at home between visits. During clinical visits, patients also completed the Asthma Specific Quality of Life Questionnaire Standardized version assessing HRQL (AQLQ(S)), the Asthma Control Questionnaire 6-item version (ACQ-6), a 9-item asthma symptom checklist, items assessing symptom severity, and a single item overall rating of satisfaction (numerical analog scale between 0 and 10). Derived total satisfaction scores were compared to scores produced by the single global treatment satisfaction item using score variation and distribution plots. Results: Qualitative results identified 11 key attributes of asthma treatment. Internal consistency for the expectations, outcomes, and satisfaction parts of the measures (11 items each) were 0.73, 0.82 and 0.95, respectively. ATSM scores were able to discriminate between control and lack of control measured by ACQ-6 scores (F = 30.09; p < 0.001); between improvement, no change, or worsening of symptoms using the 4-week diary (F = 7.05; p < 0.001); between mild, moderate and severe levels of self-reported severity of asthma (F = 2.07; p < 0.001); and levels of self-reported health status (F = 5.96; p < 0.001). Compared to the single overall satisfaction item, the ATSM satisfaction score demonstrated a broader and more normal distribution. Irrespective of the variety of treatment regimens being changed from and changed to in the normal care setting, 4 of the 11 attributes still detected statistically significant differences in (p < 0.05) levels of patient satisfaction related to their new asthma treatment regimen. Conclusion: By augmenting a satisfaction rating with the constructs that help define satisfaction with treatment (expectation, importance and actual treatment experience), the ATSM scores demonstrated greater ability to detect changes in treatment and provide a potentially useful measurement system for pharmacologic evaluation. This study was conducted using a normal care setting to identify patients undergoing a change in treatment. Therefore, the main limitations were the inability to control for efficacy of treatment, and a relatively small sample. Several individual ATSM satisfaction scores were able to detect significant levels of patient satisfaction related to their treatment, while the global satisfaction scores were unable to detect any significant differences.

Relationship Between Symptom Change, Objective Tumor Measurements, and Performance Status During Chemotherapy for Advanced Lung Cancer

PURPOSE Our objective was to identify which symptoms of advanced lung cancer are most likely to change with objective tumor measurements (progressions and responses) or changes in performance status (PS). PATIENTS AND METHODS Eighty patients with advanced non-small-cell lung cancer were studied during the first 12 weeks of chemotherapy. Symptoms were assessed weekly through telephone administration of the Functional Assessment of Cancer Therapy-Lung Symptom Index-12. Data on PS were collected from patients every 3 weeks. Symptom reports were mapped onto clinical events (progression or response as determined by clinicians) and PS assessments. RESULTS Disease progression and declining PS were associated with worsening of several symptoms. Pain, shortness of breath, cough, weight loss, and appetite loss worsened most from before to after progression. Patients with an objective response to chemotherapy reported more fatigue and difficulty breathing at response than before response. However, unlike patients who experienced progression, patients responding to chemotherapy never or rarely complained of clinically significant pain, weight loss, cough, chest tightness, nausea, or confusion before, during, or after response. With the exception of bother with side effects of treatment, confusion, and difficulty breathing, symptoms tracked fairly closely over the 12 weeks with changes in PS. Declining PS was associated with considerably more symptom worsening than unchanged or improved PS, independent of treatment response. CONCLUSION These data can help the clinician identify symptoms of lung cancer most reliably associated with objective responses and perceived changes in functional status during chemotherapy. Symptom self-reports could be used by clinicians to monitor patient status and possibly inform treatment modification.