Strategies for measuring long-term control in atopic dermatitis trials: a systematic review

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardised methods for capturing long-term control of AD. Objective: To identify how long-term control has been captured in published randomised controlled trials (RCTs). Resultswill initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. Methods: Systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of ≥3 months, at least one outcome measure recorded at ≥3 time-points, full paper available, and published in English. Results: 101/ 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%); and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly for trials including flare data (21/52). Medication-use was recorded based on quantity, potency and frequency of application. Limitations: Included RCT data only Conclusion: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes

Is speed of healing a good predictor of eventual healing of pyoderma gangrenosum?

Background: Pyoderma gangrenosum is a rare inflammatory skin condition. The STOPGAP studies compared treatments for pyoderma gangrenosum using a primary outcome of healing speed at 6 weeks. Objective: Using data from both studies we assessed the predictive value of three early predictors for healing at 6 months - speed of healing, Investigator Global Assessment and resolution of inflammation, recorded at 2 and 6 weeks. Methods: Logistic regression models were applied and the effectiveness of the three measures was assessed through estimating the positive (PPV) and negative predictive values (NPV) and the area under the receiver operating characteristic curve (AUC). Results: The PPV and NPV at 6 weeks were 63.5% (95% CI:52.4%, 73.7%) and 74.6% (95% CI:62.5%, 84.5%) respectively for speed of healing; 80% (95% CI:68.7%, 88.6%) and 74.2% (95% CI:64.1%, 2.7%) for IGA; and 72.1% (95% CI:59.9%, 82.3%) and 68.1% (95% CI:57.7%, 77.3%) for resolution of inflammation. Investigator Global Assessment had the best combined PPV, NPV and AUC at 2 and 6 weeks. Limitations: We were limited by data available from the STOP GAP trial and cohort study. Conclusion: Speed of healing, Investigator Global Assessment and resolution of inflammation were all shown to be good predictors of eventual healing

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Refining and optimising a behavioural intervention to support endocrine therapy adherence (ROSETA) in UK women with breast cancer : protocol for a pilot fractional factorial trial

Introduction Women with breast cancer who do not adhere to adjuvant endocrine therapy (AET) have increased risks of mortality and recurrence. There are multiple barriers to AET adherence, including medication side-effects, beliefs about medication, memory and psychological distress. We developed four intervention components, each targeting a different barrier. This pilot trial is part of the preparation phase of the Multiphase Optimisation Strategy, and aims to establish key trial parameters, establish intervention component adherence, establish availability and feasibility of outcome and process data, estimate variability in planned outcome measures and estimate cost of developing and delivering each intervention component. Methods and analysis The four intervention components are as follows: short message service text reminders (target: memory); a written information leaflet (target: medication beliefs); a guided self-help Acceptance and Commitment Therapy programme (target: psychological flexibility to reduce distress) and a self-management website (target: side-effect management). To evaluate the feasibility of recruitment, acceptability of the intervention components and the availability of outcome data, we will conduct a multisite, exploratory pilot trial using a 2 4-1 fractional factorial design, with a nested process evaluation. We will randomise 80 women with early-stage breast cancer who have been prescribed AET to one of eight experimental conditions. This will determine the combination of intervention components they receive, ranging from zero to four, with all conditions receiving usual care. Key outcomes of interest include medication adherence and quality of life. Progression to the optimisation phase will be based on predefined criteria for consent rates, patient adherence to intervention components and availability of medication adherence data. Ethics and dissemination The study was reviewed by the Wales Research Authority Research Ethics Committee 3 (21/WA/0322). Written informed consent will be obtained from all patients before randomisation. The results of this trial will be disseminated in a peer-reviewed journal. Trial registration number ISRTCN10487576

Supporting adjuvant endocrine therapy adherence in women with breast cancer : the development of a complex behavioural intervention using Intervention Mapping guided by the Multiphase Optimisation Strategy

Background: Adjuvant endocrine therapy (AET) reduces the risk of breast cancer recurrence and mortality. However, up to three-quarters of women with breast cancer do not take AET as prescribed. Existing interventions to support adherence to AET have largely been unsuccessful, and have not focused on the most salient barriers to adherence. This paper describes the process of developing four theory-based intervention components to support adherence to AET. Our aim is to provide an exemplar of intervention development using Intervention Mapping (IM) with guidance from the Multiphase Optimisation Strategy (MOST). Methods: Iterative development followed the six-stage IM framework with stakeholder involvement. Stage 1 involved a literature review of barriers to adherence and existing interventions, which informed the intervention objectives outlined in Stage 2. Stage 3 identified relevant theoretical considerations and practical strategies for supporting adherence. Stage 4 used information from Stages 1-3 to develop the intervention components. Stages 1-4 informed a conceptual model for the intervention package. Stages 5 and 6 detailed implementation considerations and evaluation plans for the intervention package, respectively. Results: The final intervention package comprised four individual intervention components: Short Message Service to encourage habitual behaviours surrounding medication taking; an information leaflet to target unhelpful beliefs about AET; remotely delivered Acceptance and Commitment Therapy-based guided self-help to reduce psychological distress; and a website to support self-management of AET side-effects. Considerations for implementation within the NHS, including cost, timing and mode of delivery were outlined, with explanation as to how using MOST can aid this. We detail our plans for the final stage of IM which involve feasibility testing. This involved planning an external exploratory pilot trial using a 24-1 fractional factorial design, and a process evaluation to assess acceptability and fidelity of intervention components. Conclusions: We have described a systematic and logical approach for developing a theoretically informed intervention package to support medication adherence in women with breast cancer using AET. Further research to optimise the intervention package, guided by MOST, has the potential to lead to more effective, efficient and scalable interventions

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention