Thys van der Molen

Development, validity and responsiveness of the Clinical COPD Questionnaire

BackgroundThe new Global Obstructive Lung Disease (GOLD) guidelines advice to focus treatment in Chronic Obstructive Pulmonary Disease (COPD) on improvement of functional state, prevention of disease progression and minimization of symptoms. So far no validated questionnaires are available to measure symptom and functional state in daily clinical practice. The aim of this study was to develop and validate the Clinical COPD Questionnaire (CCQ).MethodsQualitative research with patients and clinicians was performed to generate possible items to evaluate clinical COPD control. Thereafter, an item reduction questionnaire was sent to 77 international experts. Sixty-seven experts responded and the 10 most important items, divided into 3 domains (symptoms, functional and mental state) were included in the CCQ (scale: 0 = best, 6 = worst).ResultsCross-sectional data were collected from 119 subjects (57 COPD, GOLD stage I-III; 18 GOLD stage 0 and 44 (ex)smokers). Cronbachs α was high (0.91). The CCQ scores in patients (GOLD 0-III) were significantly higher than in healthy (ex)smokers. Furthermore, significant correlations were found between the CCQ total score and domains of the SF-36 (ρ = 0.48 to ρ = 0.69) and the SGRQ (ρ = 0.67 to ρ = 0.72). In patients with COPD, the correlation between the CCQ and FEV1%pred was ρ =-0.49. Test-retest reliability was determined in 20 subjects in a 2-week interval (Intra Class Coefficient = 0.94). Thirty-six smokers with and without COPD showed significant improvement in the CCQ after 2 months smoking cessation, indicating the responsiveness of the CCQ.ConclusionThe CCQ is a self-administered questionnaire specially developed to measure clinical control in patients with COPD. Data support the validity, reliability and responsiveness of this short and easy to administer questionnaire.

Clinical and economic impact of non- adherence in COPD: A systematic review

BACKGROUNDnMedication for Chronic Obstructive Pulmonary Disease (COPD) has shown to substantially reduce symptoms and slow progression of disease. However, non-adherence to medication is common and associated with worsened clinical and economic outcomes.nnnOBJECTIVEnThe objective of this study was to perform a systematic review of published literature to assess the impact of non-adherence to COPD medication on clinical and economic outcomes.nnnMETHODSnA search in PubMed and Web of Science databases was conducted of original studies published from database inception to 2012. Studies must report on the association between adherence to COPD medication and outcomes, published in English in peer-reviewed journals and full texts needed to be available.nnnRESULTSnTwelve full articles were included in the review. Most studies were retrospective database studies. Seven studies reported on the association between adherence and clinical outcomes, two on mortality, three on costs, four on quality of life and one on work productivity. Results indicated a clear association between adherence and both clinical and economic outcomes. Evidence from studies revealed increased hospitalizations, mortality, quality of life and loss of productivity among non-adherent patients.nnnCONCLUSIONnThis review revealed a clear association between non-adherence to COPD medication and worsened clinical and economic outcomes making non-adherent patients a priority for cost-effective interventions.

Reassessing the Evidence Hierarchy in Asthma: Evaluating Comparative Effectiveness

Classical randomized controlled trials are the gold standard in medical evidence because of their high internal validity. However, their necessarily strict design can limit their external validity and the ability to extrapolate these data to real world patients. Therefore, alternatively designed studies may play a complementary role in evaluating the comparative effectiveness of therapies in nonidealized patients in more naturalistic, real world settings. Observational studies have high external validity and can evaluate real world outcomes. Their strength lies in hypothesis generation and testing and in identifying areas in which further clinical trials may be required. Pragmatic trials are designed to maximize applicability of trial results to usual care settings by relying on clinically important outcomes and enrolling a wide range of participants. A combination of these approaches is preferable and necessary.

The use of questionnaires for measuring patient-reported side effects of drugs: its importance and methodological challenges.

Patient-reported outcomes such as Quality of Life often play an important part in the efficacy assessment of drug treatment. Although instruments that measure quality of life can detect the positive effects of treatments on health status, they may not measure the effect of negative treatment-related symptoms. Patients often fail to spontaneously report common or clinically mild drug-related symptoms, even though the same symptoms can result in the stopping or skipping of prescribed doses. Therefore, as with quality of life assessments, the perception of patients on possible side effects of treatments is best captured by the use of self-report questionnaires. There are substantial challenges with creating well-validated, relevant questionnaires that capture the full range of patient-reported symptoms and signs. A review of 13 existing instruments showed that many patient-rated side effect questionnaires had been developed, often to a high standard, using well-established psychometric methods. However, there were some inconsistencies in the methods used by the questionnaire developers, indicating the need for standardisation when creating new, or adapting previous, instruments. Even with their current deficits, it is important that patient-reported side effect questionnaires be used more in drug development, health outcomes research and resource allocation; all with the ultimate aim of improving quality of patient care.Patient‐reported outcomes such as Quality of Life often play an important part in the efficacy assessment of drug treatment. Although instruments that measure quality of life can detect the positive effects of treatments on health status, they may not measure the effect of negative treatment‐related symptoms. Patients often fail to spontaneously report common or clinically mild drug‐related symptoms, even though the same symptoms can result in the stopping or skipping of prescribed doses. Therefore, as with quality of life assessments, the perception of patients on possible side effects of treatments is best captured by the use of self‐report questionnaires. There are substantial challenges with creating well‐validated, relevant questionnaires that capture the full range of patient‐reported symptoms and signs. A review of 13 existing instruments showed that many patient‐rated side effect questionnaires had been developed, often to a high standard, using well‐established psychometric methods. However, there were some inconsistencies in the methods used by the questionnaire developers, indicating the need for standardisation when creating new, or adapting previous, instruments. Even with their current deficits, it is important that patient‐reported side effect questionnaires be used more in drug development, health outcomes research and resource allocation; all with the ultimate aim of improving quality of patient care. Copyright

A self-rating scale for patient-perceived side effects of inhaled corticosteroids

BackgroundPatient-reported side effect questionnaires offer a simple method for the systematic measurement of drug-related side effects. In order to measure patients inhaled corticosteroids (ICS) related side effect perceptions the 14-day retrospective Inhaled Corticosteroid Questionnaire (ICQ) was developed. In this research we aim to assess the construct validity and reliability of the ICQ and test its responsiveness to dose changes in adult asthma patients.MethodsIn a cross-sectional study, current inhaler users with asthma completed the ICQ (27 with non ICS inhaler; 61 BDP equivalent daily ICS low dose ≤400 μg; 62 mid dose 401–800 μg; and 105 with high dose >800 μg). We generated 3 construct validity hypotheses: 1) a hierarchical dose-response pattern for scoring of the individual items on the ICQ, and statistically significant differences in the scores of each of the 15 ICQ domains by ICS dose group 2) an association between ICS dose and ICQ scoring after adjusting for appropriate confounders in multiple regression; 3) greater convergence between local side effect domains than between systemic and local domains of the scale. Test-retest reliability was assessed on a randomly selected subgroup of patients (n = 73) who also completed the ICQ a second time after 7 days. In a separate longitudinal study, 61 patients with asthma completed the ICQ at baseline and after changing their daily ICS dose, at 2- and 6- months, in order to test the ICQs responsiveness.ResultsAll three construct validity hypotheses were well supported: 1) a statistically significant difference existed in scores for 14 domains, the high ICS dose group scoring highest; 2) ICS dose independently predicted ICQ scoring after adjusting for confounders; 3) greater convergence existed between local ICQ domains than between local and systemic domains. The ICQ had good reproducibility: test-retest intraclass correlation coefficients were ≥0.69 for all but the Facial Oedema domain. In the longitudinal study, ICQ scores for Voice Problems changed significantly at 2- and 6-months from baseline and other ICQ domains displayed trends in scoring change accordant with dose modulation at 6-months.ConclusionThe ICQ has good dose-related discriminative properties, is valid, reliable, and shows potential responsiveness to ICS dose change.

Patient-reporting of side effects may provide an important source of information in clinical practice.

Dear Editor, n nThe results of the recent study by Lampela et al. [1] showing a great disparity between adverse effects reported by physicians and those reported by patients is, in our opinion, not surprising. However, the direction of the disparity found in this study is intriguing. The side effects reported by 404 randomly selected elderly patients (≥75 years of age; mean drug use: 6.5 drugs) were compared with those identified by a physician. Overall physician-reporting of side effects (patients with one or more side effect = 24%) was double that of patient-reporting (11.4%). This is indeed surprising because it is well-documented that physicians often under-report [2] – and may even fail to discuss [3] – side effects in clinical settings. n nWith more careful reading of the article a number of explanations for this finding emerge. Firstly, the study physician who assessed patients was highly trained and motivated to actively search for side effects, as the authors clearly state. In contrast, the patients had received no training about potential side effects, making it unlikely that unexpected side effects, such as cardiovascular or urinary problems, would be spontaneously reported. All data in the paper were from the intervention group, but data from the control group were not reported. This is unfortunate because control data would have provided important information about the rates of side effect reporting in patients who did not receive the intervention and from the physicians treating them. Secondly, participating patients reported their side effects in the context of a randomised intervention study, but patients taking part in trials may under-report their symptoms [4]. Thirdly, the method of assessing a side effect can be crucial to the level of patient-reporting achieved. The ‘open-question method’ (for example: “have you had side effects?”), which is similar to that used in this study, may under-estimate patients’ experiences of side effects while the ‘rating-scale method’ (in which the patient is provided with a questionnaire listing potential side effects) can drastically increase the patient’s ability to report the side effects they experience [5]. n nIn our view these interesting results from Lampela et al. should be regarded as a comparison of side effect reporting between expert-physician and naive-patient using the open-question method. Such results are unlikely to reflect what could be achieved with careful questioning of patients about side effects. n nFinally, the authors conclude, perhaps correctly, that elderly persons tend to neglect drug side effects. The inclusion of a comparison group of younger patients in this study would have been useful to support this supposition. n nIn conclusion, this study raises an important issue about disparity between physician- and patient-reporting of side effects. However, the results of this research represent optimal physician-reporting of side effects, and it is important that readers are aware that in everyday clinical practice there are often sub-optimal conditions for physician-reporting. Furthermore, patient-reporting of side effects is considered to be a useful source of information on side effects in pharmacovigilance [6] and clinical practice [7]. Thus, the authors’ assertion that reliance on patient-reporting may lead to “many avoidable drug-related adverse effects (which) may be overlooked resulting in unnecessary distress to the patient” seems unfairly dismissive, considering that with the use of the appropriate methods (e.g. rating-scales), patient-reporting can be an important source of information about side effects in the context of real-life clinical practice.

Personality Influences the Reporting of Side Effects of Inhaled Corticosteroids in Asthma Patients

Rationale. Negative affectivity is a measure of anxiety associated with increased reporting of symptoms. Few studies have explored this association with respect to drug-induced symptoms in patients taking medication for a chronic disease in real life. Objectives. In this cross-sectional study we examined the relationship between negative affectivity and self-reported side effects of inhaled corticosteroids in patients with asthma. We also investigated differential associations due to side effect type (subjective versus observable side effects) and treatment impact (i.e., hierarchical dosing). Methods. A total of 228 asthma patients, taking inhaled corticosteroids, completed scales measuring inhaled corticosteroid-induced side effects (Inhaled Corticosteroid Questionnaire scored: 0 = none; 100 = worst) and negative affectivity (Positive and Negative Affect Schedule scored: 10–50). Patients were grouped into low, average, and high negative affectivity groups based on published norms. Results. Patients high in negative affectivity reported significantly greater (p < 0.001) side effects (median score 20.5 (IQR: 11.4–33.0) than the groups of patients scoring lower on this measure (low negative affectivity: 7.1 (3.1–15.6); average: 13.3 (4.9–23.3)). The relationship between negative affectivity and side effects was stronger among patients taking low (r = 0.40–0.45) rather than mid to high inhaled corticosteroid doses (r = 0.16–0.28). Conclusions. Asthma patients with higher negative affectivity using inhaled corticosteroids report increased medication-induced symptoms. Clinicians should be aware that aside from inhaled corticosteroid dosage, the personality of the patient is an important factor in the reporting of drug-related side effects.