Does co-payment for inhaler devices affect therapy adherence and disease outcomes? A historical, matched cohort study.

BACKGROUND: Adherence to asthma and chronic obstructive pulmonary disease (COPD) treatment has been shown to depend on patient-level factors, such as disease severity, and medication-level factors, such as complexity. However, little is known about the impact of prescription charges - a factor at the health care system level. This study used real-life data to investigate whether co-payment affects adherence (implementation and persistence) and disease outcomes in patients with asthma or COPD. METHODS: A matched, historical cohort study was carried out using two UK primary care databases. The exposure was co-payment for prescriptions, which is required for most patients in England but not in Scotland. Two comparison cohorts were formed: one comprising patients registered at general practices in England and the other comprising patients registered in Scotland. Patients aged 20-59 years with asthma, or 40-59 years with COPD, who were initiated on fluticasone propionate/salmeterol xinafoate, were included, matched to patients in the opposite cohort, and followed up for 1 year following fluticasone propionate/salmeterol xinafoate initiation. The primary outcome was good adherence, defined as medication possession ratio ≥80%, and was analyzed using conditional logistic regression. Secondary outcomes included exacerbation rate. RESULTS: There were 1,640 patients in the payment cohort, ie, England (1,378 patients with asthma and 262 patients with COPD) and 619 patients in the no-payment cohort, ie, Scotland (512 patients with asthma and 107 patients with COPD). The proportion of patients with good adherence was 34.3% and 34.9% in the payment and no-payment cohorts, respectively, across both disease groups. In a multivariable model, no difference in odds of good adherence was found between the cohorts (odds ratio, 1.04; 95% confidence interval, 0.85-1.27). There was also no difference in exacerbation rate. CONCLUSION: There was no difference in adherence between matched patients registered in England and Scotland, suggesting that prescription charges do not have an impact on adherence to treatment.

Inhaler Errors in the CRITIKAL Study: Type, Frequency, and Association with Asthma Outcomes.

BACKGROUND: Poor inhaler technique has been linked to poor asthma outcomes. Training can reduce the number of inhaler errors, but it is unknown which errors have the greatest impact on asthma outcomes. OBJECTIVE: The CRITical Inhaler mistaKes and Asthma controL study investigated the association between specific inhaler errors and asthma outcomes. METHODS: This analysis used data from the iHARP asthma review service-a multicenter cross-sectional study of adults with asthma. The review took place between 2011 and 2014 and captured data from more than 5000 patients on demographic characteristics, asthma symptoms, and inhaler errors observed by purposefully trained health care professionals. People with asthma receiving a fixed-dose combination treatment with inhaled corticosteroids and long-acting beta agonist were categorized by the controller inhaler device they used-dry-powder inhalers or metered-dose inhalers: inhaler errors were analyzed within device cohorts. Error frequency, asthma symptom control, and exacerbation rate were analyzed to identify critical errors. RESULTS: This report contains data from 3660 patients. Insufficient inspiratory effort was common (made by 32%-38% of dry-powder inhaler users) and was associated with uncontrolled asthma (adjusted odds ratios [95% CI], 1.30 [1.08-1.57] and 1.56 [1.17-2.07] in those using Turbohaler and Diskus devices, respectively) and increased exacerbation rate. In metered-dose inhaler users, actuation before inhalation (24.9% of patients) was associated with uncontrolled asthma (1.55 [1.11-2.16]). Several more generic and device-specific errors were also identified as critical. CONCLUSIONS: Specific inhaler errors have been identified as critical errors, evidenced by frequency and association with asthma outcomes. Asthma management should target inhaler training to reduce key critical errors.

Cost comparison of asthma treatments in 12-week study: caution about matching and short observational follow-up.

In the absence of randomisation, observational studies must take extra care to create treatment groups that are comparable in terms of key characteristics. Various matching methods exist which can create sound comparisons, minimising confounding where possible. A recent observational study by Dal Negro et al. carried out a cost analysis comparing two asthma medications. They report strong conclusions which favour one treatment over the other, however they include little discussion on the limitations of their study. The purpose of this letter is to comment on the weaknesses of the study design, including the level of matching used, and to urge readers to consider these issues alongside the interpretation of results.

Use of an embedded, micro-randomised trial to investigate non-compliance in telehealth interventions.

BACKGROUND/AIMS: Many types of telehealth interventions rely on activity from the patient in order to have a beneficial effect on their outcome. Remote monitoring systems require the patient to record regular measurements at home, for example, blood pressure, so clinicians can see whether the patient's health changes over time and intervene if necessary. A big problem in this type of intervention is non-compliance. Most telehealth trials report compliance rates, but they rarely compare compliance among various options of telehealth delivery, of which there may be many. Optimising telehealth delivery is vital for improving compliance and, therefore, clinical outcomes. We propose a trial design which investigates ways of improving compliance. For efficiency, this trial is embedded in a larger trial for evaluating clinical effectiveness. It employs a technique called micro-randomisation, where individual patients are randomised multiple times throughout the study. The aims of this article are (1) to verify whether the presence of an embedded secondary trial still allows valid analysis of the primary research and (2) to demonstrate the usefulness of the micro-randomisation technique for comparing compliance interventions. METHODS: Simulation studies were used to simulate a large number of clinical trials, in which no embedded trial was used, a micro-randomised embedded trial was used, and a factorial embedded trial was used. Each simulation recorded the operating characteristics of the primary and secondary trials. RESULTS: We show that the type I error rate of the primary analysis was not affected by the presence of an embedded secondary trial. Furthermore, we show that micro-randomisation is superior to a factorial design as it reduces the variation caused by within-patient correlation. It therefore requires smaller sample sizes - our simulations showed a requirement of 128 patients for a micro-randomised trial versus 760 patients for a factorial design, in the presence of within-patient correlation. CONCLUSION: We believe that an embedded, micro-randomised trial is a feasible technique that can potentially be highly useful in telehealth trials.

Design of telehealth trials--introducing adaptive approaches.

BACKGROUND: The field of telehealth and telemedicine is expanding as the need to improve efficiency of health care becomes more pressing. The decision to implement a telehealth system is generally an expensive undertaking that impacts a large number of patients and other stakeholders. It is therefore extremely important that the decision is fully supported by accurate evaluation of telehealth interventions. OBJECTIVE: Numerous reviews of telehealth have described the evidence base as inconsistent. In response they call for larger, more rigorously controlled trials, and trials which go beyond evaluation of clinical effectiveness alone. The aim of this paper is to discuss various ways in which evaluation of telehealth could be improved by the use of adaptive trial designs. RESULTS: We discuss various adaptive design options, such as sample size reviews and changing the study hypothesis to address uncertain parameters, group sequential trials and multi-arm multi-stage trials to improve efficiency, and enrichment designs to maximise the chances of obtaining clear evidence about the telehealth intervention. CONCLUSION: There is potential to address the flaws discussed in the telehealth literature through the adoption of adaptive approaches to trial design. Such designs could lead to improvements in efficiency, allow the evaluation of multiple telehealth interventions in a cost-effective way, or accurately assess a range of endpoints that are important in the overall success of a telehealth programme.