On legitimacy in impact assessment: An epistemologically-based conceptualisation

Impact assessment (IA) is carried out as an ex ante process to inform decision-making. It includes requirements for engagement with stakeholders (including the public) regarding actions proposed by a proponent. A key issue with the various stakeholders involved is the perceived legitimacy of the IA, which can have implications both for the reputation of the proponent, and the likelihood of conflict over the decision. But the understanding of legitimacy in the IA literature has changed over time in line with an ontological shift from positivism (that scientifically generated information leads to better informed decisions) to the post-positivist acknowledgement of the limitations of scientific method whereby assumptions must be subject to transparency, deliberation and openness. This has led to an epistemological shift towards greater subjectivism which, we suggest, has created new opportunities (which have been realised in political decision-making) to subvert knowledge through the increased use of the Internet and social media. To address the potential for such subversion of legitimacy, we seek to conceptualise legitimacy in the IA context through framing IA around a critical realist ontology and a reliabilist virtue epistemology. This allows us to identify ‘knowledge legitimacy’ as an equally important component of IA legitimacy along with organisational legitimacy. We conceptualise knowledge legitimacy through literature review drawing on rich understandings of knowledge from IA and other fields of research in order to develop a four-dimensional typology. This includes the dimensions of: knowledge accuracy; knowledge restriction; knowledge diffusion; and knowledge spectrum. This is the first theoretically grounded attempt to understand legitimacy in IA. It is hoped that it will provoke discussion in the IA community to further advance theoretical understandings of IA and legitimacy of practice

Patient-centred innovation for multimorbidity care : mixed-methods, randomized trial and qualitative study of the patients’ experience

Background Patient-centred interventions to help patients with multimorbidity have had mixed results. Aim To assess the effectiveness of a provider-created, patient-centred, multi-provider case conference with follow-up, and understand underwhal circumstances it worked. and did not work Design and setting Mixed-methods design with a pragmatic randomised trial and qualitative study. involving nine urban primary care sites in Ontario, Canada. Method Patients aged 18-80 years with >= 3 chronic conditions were referred to the Telemedicine IMPACT Plus intervention; a nurse and patient planned a multi provider case conference during which a care plan could be created. The patients were randomised into an intervention or control group. Two subgroup analyses and a fidelity assessment were conducted, with the primary outcomes at 4 months being self-management and self-efficacy. Secondary outcomes were mental and physical health status, quality of life, and health behaviours. A thematic analysis explored the patients' experiences of the intervention. Results A total of 86 patients in the intervention group and 77 in the control group showed no differences, except that the intervention improved mental health status in the subgroup with an annual income of >= C$50 000 [beta-coefficient 11.003, P= 0.006]. More providers and follow-up hours were associated with poorer outcomes. Five themes were identified in the qualitative study: valuing the team, patients feeling supported. receiving a follow-up plan, being offered new and helpful additions to their treatment regimen, and experiencing positive outcomes. Conclusion Overall, the intervention showed improvements only for patients who had an annual income of >= C$50 000, implying a need to address the Wsis of intervention components not covered by existing health policies. Findings suggest a need to optimise learn composition by revising the number and type of providers according to patient preferences and to enhance the hours of nurse follow-up to better support the patient in carrying out the case conference's recommendations

Clinical implications and predictive values of early PASI responses to tildrakizumab in patients with moderate-to-severe plaque psoriasis

Objective To evaluate whether early Psoriasis Area Severity Index (PASI) improvements can predict week 28 tildrakizumab responders and nonresponders. Methods Psoriasis patients pooled from two tildrakizumab phase 3 trials randomized to receive tildrakizumab 100 mg at weeks 0, 4, 16, and 28 were included. Patients were grouped by week 28 PASI responses (<50, 50–74, 75–89, and 90–100). PASI improvements from baseline at weeks 4 and 16 were analyzed for each response group. Results Of 575 patients included, 8.3%, 14.3%, 23.8%, and 53.6%, respectively, achieved PASI <50, 50–74, 75–89, and 90–100 at week 28. Of patients with PASI <50 at week 16, 85% did not achieve PASI ≥75 at week 28 (nonresponders). Rapid response, defined as PASI ≥50 at week 4 (after a single tildrakizumab dose), was observed in 41% of patients. Of these patients, 87% were week 28 responders (PASI ≥75); 67% were ‘super responders’ (PASI 90–100). Among week 28 responders and super responders, 45% and 50% achieved PASI ≥50 at week 4, respectively. Conclusions Tildrakizumab week 28 nonresponders can be identified by week 16 PASI response. PASI improvements as early as week 4 can predict patients’ week 28 PASI improvement status

A Machine Learning-Based Test for Predicting Response to Psoriasis Biologics

Objective: This study was designed to develop and prospectively validate a machine learning based algorithm that could predict patient response to the most common biologic drug classes used in the management of psoriasis patients. This type of tool would allow clinicians to have greater confidence that a given patient will respond to a specific drug class, which could lead to improved health outcomes and reduced wasted healthcare spend.&#x0D; Methods: Patients were enrolled into one of two observational studies (STAMP studies) where dermal biomarker patches (DBPs) were applied at baseline prior to drug exposure, followed by clinical evaluations at 12 weeks after exposure. PASI measurements were made at baseline and 12 weeks to evaluate clinical response to a clinical phenotype. Responders were defined as those who reached PASI75 at 12 weeks. The transcriptomes obtained from the DBPs were sequenced and analyzed to derive and/or validate classifiers for each biologic class, which were then combined to yield predictive responses for all three biologic drug classes (IL-23i, IL-17i, and TNFai).&#x0D; Results: A total of 242 psoriasis patients were enrolled in these studies, including 118 patients (49.6%) treated with IL-23i, 79 patients (33.2%) treated with IL-17i, 35 patients (14.7%) treated with TNFai, and 6 patients (2.5%) treated with IL-12/23i. The IL-23i predictive classifier was developed from the earlier enrolled patients and independently validated with the latter enrolled patients. IL-17i and TNFai predictive classifiers were developed using publicly available datasets and independently validated with patients from the STAMP studies. In the independent validation, positive predictive values for three classifiers (IL-23i, IL-17i, and TNFai) were 93.1%, 92.3% and 85.7% respectively. Over the entire cohort, 99.5% of patients were predicted to respond to at least one drug class.&#x0D; Conclusion: This study demonstrates the power of using baseline dermal biomarkers and machine learning methods as applied to the prediction of psoriasis biologic prior to drug exposure. Using this test, patients, physicians, and the health care system all can benefit in distinct ways. Precision medicine can be realized for individual patients as most will likely respond to their prescribed biologic the first time. Physicians can prescribe these drugs with increased confidence, and the healthcare system will realize lower net costs as well as greatly reduced wasted spend by significantly improving initial response rates to expensive biologic therapeutics.</jats:p

OBSERVE-5 interim analysis: An observational postmarketing safety registry of etanercept for the treatment of psoriasis

BackgroundEtanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults.ObjectiveWe sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective.MethodsOBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period.ResultsA total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database.LimitationsThe registry lacks a control group, and the study is too small to measure the frequency of rare events.ConclusionEtanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed

OBSERVE-5: Observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results

BackgroundOBSERVE-5 was a 5-year Food and Drug Administration–mandated surveillance registry of patients with psoriasis.ObjectiveWe sought to assess long-term etanercept safety and effectiveness.MethodsPatients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database.ResultsFor 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years.LimitationsNo internal comparator group was included; rare events may not have been detected.ConclusionNo new safety signals were observed with long-term, real-world etanercept use

Patient-centred innovation for multimorbidity care: A mixed-methods, randomised trial and qualitative study of the patients’ experience

Background Patient-centred interventions to help patients with multimorbidity have had mixed results. Aim To assess the effectiveness of a provider-created, patient-centred, multi-provider case conference with follow-up, and understand under what circumstances it worked, and did not work. Design and setting Mixed-methods design with a pragmatic randomised trial and qualitative study, involving nine urban primary care sites in Ontario, Canada. Method Patients aged 18–80 years with ≥3 chronic conditions were referred to the Telemedicine IMPACT Plus intervention; a nurse and patient planned a multi-provider case conference during which a care plan could be created. The patients were randomised into an intervention or control group. Two subgroup analyses and a fidelity assessment were conducted, with the primary outcomes at 4 months being self-management and self-efficacy. Secondary outcomes were mental and physical health status, quality of life, and health behaviours. A thematic analysis explored the patients\u27 experiences of the intervention. Results A total of 86 patients in the intervention group and 77 in the control group showed no differences, except that the intervention improved mental health status in the subgroup with an annual income of ≥C$50 000 (β-coefficient 11.003, P = 0.006). More providers and follow-up hours were associated with poorer outcomes. Five themes were identified in the qualitative study: valuing the team, patients feeling supported, receiving a follow-up plan, being offered new and helpful additions to their treatment regimen, and experiencing positive outcomes. Conclusion Overall, the intervention showed improvements only for patients who had an annual income of ≥C$50 000, implying a need to address the costs of intervention components not covered by existing health policies. Findings suggest a need to optimise team composition by revising the number and type of providers according to patient preferences and to enhance the hours of nurse follow-up to better support the patient in carrying out the case conference’s recommendations