How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients.

OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.

An international multi-centre analysis of current prescribing practices and shared decision-making in psoriatic arthritis.

OBJECTIVES: Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. METHODS: The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). RESULTS: 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. CONCLUSIONS: Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT05171270.

EFSPI/PSI working group on data sharing: accessing and working with pharmaceutical clinical trial patient level datasets - a primer for academic researchers.

BACKGROUND: Access to patient level datasets from clinical trial sponsors continues to be an important topic for the Pharmaceutical Industry as well as academic institutions and researchers. How to make access to patient level data actually happen raises many questions from the perspective of the researcher. METHODS: Patient level data access models of all major pharmaceutical companies were surveyed and recommendations made to guide academic researchers in the most efficient way through the process of requesting and accessing patient level data. RESULTS: The key considerations for researchers covered here are finding information; writing a research proposal to request data access; the review process; how data are shared; and the expectations of the data holder. A lot of clinical trial information is available on public registries and so these are great sources of information. Depending on the research proposal the required information may be available in Clinical Study Reports and therefore patient level data may not need to be requested. Many data sharing systems have an electronic form or template but in cases where these are not available the proposal needs to be created as a stand-alone document outlining the purpose, statistical analysis plan, identifying the studies for which data are required, the research team members involved, any conflicts of interest and the funding for the research. There are three main review processes - namely having an internal review board, external review board selected by the data holder or an external review board selected by a third party. Data can be shared through Open access i.e. on a public website, direct sharing between the data holder and the researcher, controlled access or the data holder identifies a contract organization to access the data and perform the analyses on behalf of the researcher. The data that are shared will have accompanying documentation to assist the researcher in understanding the original clinical trial and data collection methods. The data holder will require a legally binding data sharing agreement to be set up with the researcher. Additionally the data holder may be available to provide some support to the researcher if questions arise. CONCLUSION: Whilst the benefits and value of patient level data sharing have yet to be fully realised, we hope that the information outlined in this article will encourage researchers to consider accessing and re-using clinical trial data to support their research questions.

Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial.

Venous leg ulcers (VLUs) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose-response efficacy of the human synthetic peptide LL-37 in the treatment of hard-to-heal VLUs. This first-in-man trial included 34 participants with VLUs and comprised a 3-week, open-label, run-in period on placebo, followed by a 4-week randomized double-blind treatment phase with twice weekly applications of LL-37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4-week follow-up. The healing rate constants for 0.5 and 1.6 mg/mL of LL-37 were approximately six- and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). Square-root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (p < 0.001 and p = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of LL-37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL-37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations.

Utility values in health technology assessments: a statistician's perspective.

This paper provides an introduction to utilities for statisticians working mainly in clinical research who have not had experience of health technology assessment work. Utility is the numeric valuation applied to a health state based on the preference of being in that state relative to perfect health. Utilities are often combined with survival data in health economic modelling to obtain quality-adjusted life years. There are several methods available for deriving the preference weights and the health states to which they are applied, and combining them to estimate utilities, and the clinical statistician has valuable skills that can be applied in ensuring the robustness of the trial design, data collection and analyses to obtain and handle this data. In addition to raising awareness of the subject and providing source references, the paper outlines the concepts and approaches around utilities using examples, discusses some of the key issues, and proposes areas where statisticians can collaborate with health economic colleagues to improve the quality of this important element of health technology assessment.

A cluster randomized study of the safety of integrated treatment of trachoma and lymphatic filariasis in children and adults in Sikasso, Mali.

BACKGROUND: Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas. METHODOLOGY/FINDINGS: 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and "other signs/symptoms"). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone. CONCLUSIONS: These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01586169.

Laboratory-based non-clinical comparison of occlusion rates using three rapid-acting insulin analogs in continuous subcutaneous insulin infusion catheters using low flow rates.

BACKGROUND: Rapid-acting analog insulin is used increasingly for continuous subcutaneous insulin infusion therapy (CSII). As the choice of insulin may be a determinant of catheter occlusion, we compared rates of early and late occlusion of a standard CSII catheter with three insulin analogs in a laboratory-based setting. METHODS: Twenty-four pumps were used for the study. Each insulin analog (glulisine, lispro, and aspart) was assigned to eight pumps in a randomized order for each of nine runs of 5-day duration. Pumps were primed to receive a basal dose of 0.1 IU/h with a bolus dose of 2 IU given three times each day. Pumps were placed in an incubator to maintain temperature in the range of 32 to 36 degrees C. RESULTS: Over the entire study period, there were 48 occlusions. Early occlusions (within 72 hours) occurred during five of the nine runs with no evidence of any difference between insulins (p = .27); there were no occlusions before 48 hours. Over the whole of the 5-day infusion period, the probabilities of overall occlusion for each insulin were 40.9% [28 to 55%, 95% confidence interval (CI)] for glulisine, 9.2% (4 to 19.5%, 95% CI) for aspart, and 15.7% (8.1 to 28.1%, 95% CI) for lispro. All occlusions, except for three, occurred during a bolus infusion. CONCLUSIONS: During CSII under laboratory conditions, early catheter occlusions (within 72 hours) are rare and independent of the choice of insulin analog. For patients using insulin pump therapy, the importance of catheter change within 72 hours should be emphasized irrespective of the insulin used. Beyond 72 hours, the risk of occlusion differs between insulins, being more common with glulisine.