We have developed a method for estimating the minimally important difference (MID) for health status measures. Whereas the conventional approach requires patients to judge themselves relative to their memories, our method requires patients to judge themselves relative to others with the same condition. In this study we examined whether our method (based on between-patient differences) and the conventional method (based on within-patient changes) provides comparable estimates of the MID for one health status measure: the Chronic Respiratory Questionnaire. Patients with chronic obstructive pulmonary disease who were participating in a supervised respiratory rehabilitation program were included if they were in stable health (n = 112). Their mean score per question in the Chronic Respiratory Questionnaire was 4.5 (range, 1 to 7; where bigger values indicate better health). Our method estimated that the MID was 0.5 (95% confidence interval 0.4 to 0.7). This estimate was similar to the MID previously found using the conventional method. These observations support the role of the Chronic Respiratory Questionnaire for measuring patient's symptoms, the validity of our approach for assessing the MID, and an estimate on the order of 0.5 as the threshold for this particular health status measure.
For the treatment of COPD exacerbations, systemic corticosteroids are recommended in addition to short-acting bronchodilators. Although there have been several systemic reviews, many of the included studies were conducted before 2007 and a re-evaluation has not been performed since 2014. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of systemic corticosteroids in patients with COPD during exacerbations.
We searched relevant randomized control trials (RCTs) and analyzed the treatment failure, relapse, lung function, improvement in PaO2 and PaCO2, dyspnea, quality of life (QOL), length of stay in hospital and adverse events including hyperglycemia and mortality as the outcomes of interest.
We identified a total of 12 RCTs (N = 1336). Systemic corticosteroids significantly reduced the treatment failure (odds ratios; OR 0.41, 95% confidence intervals; CI 0.25 to 0.67) and hospital length of stay (mean difference; MD -1.57 days, 95% CI -2.36 to −0.78) and improved FEV1 (MD 0.18 L, 95% CI 0.08 to 0.28) and dyspnea (transitional dyspnea index; MD 1.90, 95% CI 0.26 to 3.54) in COPD exacerbations compared to placebo. However, systemic corticosteroids were associated with a significantly higher incidence of adverse events (OR 1.83, 95% CI 1.25 to 2.69) and hyperglycemia (OR 2.94, 95% CI 1.68 to 5.14).
In patients with moderate and severe COPD and severe obstructive impairment during exacerbations, systemic corticosteroids cause more adverse events, including hyperglycemia, than placebo but significantly reduce the treatment failure and hospital length of stay and improve FEV1 and dyspnea.
Interpreting observed changes over time in Patient-Reported Outcomes (PRO) measures is still considered a challenge. Indeed, concluding an observed change at group level is statistically significant does not necessarily equate this change is meaningful from the perspective of the patient. To help interpret within and/or between group changes in the measure over time, the estimation of the Minimal Important Difference (MID) of the instrument – the smallest value that patients consider as a perceived change – is useful. In the last 30 years, a plethora of methods and estimators have been proposed to derive this MID value using clinical data from sample of patients. MIDs for hundreds of PROs have been estimated, with frequently a substantial variability in the results depending on the method used. Nonetheless, a rigorous assessment of the statistical performances of numerous proposed methods for estimating MIDs by experimental design such as Monte-Carlo study has never been performed.
The purpose of this paper is to thoroughly depict a protocol for a large-scale simulation study designed to investigate the statistical performances, especially bias against a true populational value, of the common proposed estimators for MID.
This paper depicts how investigated methods and estimators were retained after the conduct of a systematic review, the design of a conceptual model that formally defines what is the true populational MID value and the translation of the conceptual model into a model allowing the simulation of responses of items to a hypothetical PRO at two times of measurement along with the response to a Patient Global Rating of Change at the second time under the constraint of a known true MID value. A statistical analysis plan is depicted in order to conclude if working hypotheses on what could be appropriate MID estimators will be verified. Strengths, assumptions, and limits of the simulation model are exposed.
Finally, we show how this protocol could be the basis for fostering future methodological research on the issue of interpreting changes in PRO measures.
There is uncertainty regarding efficacy of telehealth-based approaches in COPD patients for sustaining benefits achieved with intensive pulmonary rehabilitation (PR).
To determine whether a maintenance pulmonary telerehabilitation (TelePR) programme, after intensive initial PR, is superior to usual care in sustaining over time benefits achieved by intensive PR.
A multicentre open-label pragmatic parallel-group randomized clinical trial was conducted. Two groups were created at completion of an 8-week intensive outpatient hospital PR programme. Intervention group (IG) patients were given appropriate training equipment and instructed to perform three weekly training sessions and send performance data through an app to a web-based platform. Patients in the control group (CG) were advised to exercise regularly (usual care).
Ninety-four patients (46 IG, 48 CG) were randomized. The analysis of covariance showed non-significant improvements in 6-min walk distance [19.9 m (95% CI −4.1/+43.8)] and Chronic Respiratory Disease Questionnaire – Emotion score [0.4 points (0–0.8)] in the IG. Secondary linear mixed models showed improvements in the IG in Short Form-36 mental component summary [9.7, (4.0–15.4)] and Chronic Respiratory Disease Questionnaire – Emotion [0.5, (0.2–0.9)] scores, but there was no association between compliance and outcomes. Acute exacerbations were associated with a marginally significant decrease in 6-minute walk distance of 15.8 m (−32.3/0.8) in linear models.
The TelePR maintenance strategy was both feasible and safe but failed to show superiority over usual care, despite improvements in some HRQoL domains. Acute exacerbations may have an important negative influence on long-term physical function.
Existe incertidumbre con respecto a la eficacia de los enfoques basados en telesalud en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) para mantener los beneficios logrados con la rehabilitación pulmonar (RP) intensiva.
Determinar si un programa de telerrehabilitación pulmonar de mantenimiento (TeleRP), después de una RP inicial intensiva, es superior a la atención habitual para mantener en el tiempo los beneficios logrados por la RP intensiva.
Se realizó un ensayo clínico aleatorizado, pragmático, abierto, multicéntrico, de grupos paralelos. Se crearon 2 grupos al finalizar un programa de RP intensiva en régimen ambulatorio de 8 semanas de duración. A los pacientes del grupo de intervención (GI) se les proporcionó el equipo de entrenamiento apropiado y se les instruyó para realizar 3 sesiones de entrenamiento semanales y enviar los datos de rendimiento a través de una aplicación a una plataforma web. Se aconsejó a los pacientes del grupo de control (GC) que hicieran ejercicio regularmente (cuidado habitual).
Se aleatorizaron 94 pacientes (46 GI, 48 GC). El análisis de covarianza mostró mejoras no significativas en la distancia en la prueba de marcha de 6 min (19,9 m [IC 95%: −4,1/+43,8]) y el cuestionario de enfermedad respiratoria crónica-factor emocional (0,4 puntos [0-0,8]) en el GI. Los modelos lineales mixtos secundarios mostraron mejoras en el GI en las puntuaciones de la sección mental del SF-36 (9,7 [4,0-15,4]) y el cuestionario de enfermedad respiratoria crónica-factor emocional (0,5 puntos [0,2-0,9]), pero no se demostró asociación entre el cumplimiento y los resultados. Las exacerbaciones agudas se asociaron con una disminución marginalmente significativa en la distancia en la prueba de la marcha de 6 min de 15,8 m (−32,3/0,8) en los modelos lineales.
La estrategia de mantenimiento TeleRP fue viable y segura, pero no se demostró superioridad frente al cuidado habitual, a pesar de las mejoras en algunos aspectos en las valoraciones de la calidad de vida en relación con la salud. Las exacerbaciones agudas podrían tener una influencia negativa importante en la función física a largo plazo.
The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined.
We examined the effect of two doses of prophylactic FSS on exertional dyspnea.
In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%–45% (high dose) or 15%–25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0–10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function.
Thirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change −1.42; 95% CI −2.37, −0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change −0.47; 95% CI −1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected.
Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials.
In healthcare research an intervention may be statistically significant based on quantitative analysis; however, simultaneously it may be relatively insignificant to the health or quality of life of patients affected by a particular condition or disease being treated by the intervention – thus may be interpreted as having low clinical significance. An understanding of statistics is fundamental for evidence informed healthcare. Patient-reported outcome measures (PROMs) direct patients to evaluate aspects of their own health, including quality of life, disability and function. Data obtained from PROMs can be used to demonstrate the impact of healthcare interventions on these elements of a person's quality of life. To interpret outcome measure data for clinical decision making, a clinician must understand the concepts of statistical significance and clinical significance. This commentary explores the concepts of patient reported outcome measures (PROMs), their statistical and clinical significance, and explores their relationship with a practical example for the clinician. Limitations of research that only reports p-values and the need to consider effect size, confidence intervals, and minimal clinically important difference are also discussed. Together, these concepts can assist the clinician to evaluate whether an intervention may be suitable for their clinical practice.
This project was funded through an Ontario Career Scientist award to Dr. Redelmeier and by grants from the Ontario Thoracic Society, the National Cancer Institute of Canada, and the West Park Hospital Foundation.
