Enhancing the SUSTAINable uptake of evidence to minimise harms from alcohol and other drugs in New South Wales, Australia.

Although alcohol and other drug use is increasingly the focus of policy and research efforts, there are challenges identifying and applying evidence-based strategies to minimise harms for alcohol and other drugs in health care and community settings. These challenges include limited available research, variability across settings, and lack of 'fit' between research evidence and their intended settings. In this commentary, we describe a novel approach to develop and evaluate tailored, sustainable strategies to enhance the uptake of evidence-based activities into health services and community settings. Our approach involves four key principles: (i) identifying evidence-based alcohol and other drug harm minimisation strategies; (ii) partnering with local experts to identify and tailor strategies; (iii) implementing strategies into existing practice/infrastructure to build in sustainability; and (iv) using sustainable co-designed outcome measures including value-based health-care principles to measure uptake, feasibility and acceptability, health outcomes and economic implications. We propose that this approach offers a way forward to enhance the relevance and suitability of research in health services and community settings and has potential to be applied in other sectors.

Utilising the Implementation of Integrated Care to Develop a Pragmatic Framework for the Sustained Uptake of Service Innovations (SUSI).

The provision of integrated care (IC) across alcohol and other drug (AOD) and mental health (MH) services represents the best practice, yet the consistent delivery of IC in routine practice rarely occurs. Our hypothesis is that there is no practical or feasible systems-change approach to guide staff, researchers, or consumers through the complex transition that is required for the sustained uptake of IC across diverse clinical settings. To address this gap, we combined clinical and consumer expertise with the best available research evidence to develop a framework to drive the uptake of IC. The goal was to develop a process that is both standardised by the best available evidence and can be tailored to the specific characteristics of different health services. The result is the framework for Sustained Uptake of Service Innovation (SUSI), which comprises six core components that are applied in a specified sequence and a range of flexible activities that staff can use to deliver the core components according to their circumstances and preferences. The SUSI is evidence-based and practical, and further testing is currently underway to ensure it is feasible to implement in different AOD and MH services.

Solriamfetol Titration & AdministRaTion (START) in Patients With Narcolepsy.

PURPOSE: Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved (in the United States and European Union) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75-150 mg/d) or obstructive sleep apnea (OSA) (37.5-150 mg/d). This study characterized real-world titration strategies for patients with narcolepsy (with or without comorbid OSA) initiating solriamfetol therapy. METHODS: This virtual, descriptive study included a retrospective medical record review and qualitative survey. US-based physicians prescribing solriamfetol for EDS associated with narcolepsy or OSA participated. Data are reported for patients with narcolepsy with or without comorbid OSA (OSA alone reported separately). On the basis of medical record review, titration strategies were classified de novo (EDS medication naive), transition (switched or switching from existing EDS medication[s] to solriamfetol), or add-on (adding solriamfetol to current EDS medication[s]). The survey included open-ended questions regarding a hypothetical patient-a 32-year-old woman with narcolepsy (Epworth Sleepiness Scale score of 8) treated with 35 mg/d of amphetamine and 6 g per night of sodium oxybate who experiences non-use-limiting adverse events from amphetamine. FINDINGS: Twenty-six physicians participated: 23 provided data from 70 patients with narcolepsy (type 1, n = 24; type 2, n = 46; mean [SD] age, 40 [11] years; 57% female; 6 with comorbid OSA), and 26 responded to the hypothetical patient scenario. From the medical record review, solriamfetol therapy initiation was de novo for 19 of 70 patients (27%), transition for 31 of 70 patients (44%), and add-on for 20 of 70 patients (29%). Efficacy profile of solriamfetol was the primary reason for de novo (12 of 19 [63%]), transition (18 of 31 [58%]), and add-on (19 of 20 [95%]) initiation. Most (86%) initiated use of solriamfetol at 75 mg/d and were stable at 150 mg/d (76%). Most (67%) had 1 dose adjustment, reaching a stable dose over a median (range) of 14 (1-60) days. Physicians most often considered EDS severity (44%) when titrating. Among transitioning patients, 14 of 22 (64%) using wake-promoting agents discontinued their use abruptly, and 5 of 9 (56%) using stimulants were tapered off. At data collection, 90% continued to take solriamfetol. Regarding the hypothetical patient scenario, most physicians (81%) thought solriamfetol was appropriate, highlighting tolerability issues with current treatment and lack of symptom control as drivers for switching; however, 3 physicians (12%) did not think solriamfetol was appropriate, noting current symptoms were not severe enough and/or symptoms could be managed by increasing sodium oxybate dose; 2 (8%) thought it would depend on other factors. Physicians emphasized managing withdrawal symptoms while maintaining EDS symptom control when titrating off a stimulant and starting solriamfetol therapy. IMPLICATIONS: In a real-world study, physicians initiated solriamfetol therapy at 75 mg/d for most patients with narcolepsy, adjusted dosages once, tapered stimulants, and abruptly discontinued therapy with wake-promoting agents.

Solriamfetol Titration and AdministRaTion (START) in Patients with Obstructive Sleep Apnea: A Retrospective Chart Review and Hypothetical Patient Scenario.

INTRODUCTION: Solriamfetol (Sunosi™), a dopamine/norepinephrine reuptake inhibitor, is approved (USA and EU) to treat excessive daytime sleepiness (EDS) in adults with obstructive sleep apnea (OSA) (37.5-150 mg/day). Real-world research on solriamfetol initiation is limited. The objective of this study was to describe dosing and titration strategies used when initiating solriamfetol and to assess whether and how patient factors affected these strategies. METHODS: This descriptive study, featuring a quantitative retrospective patient chart review and hypothetical patient scenario, enrolled US-based physicians prescribing solriamfetol for EDS associated with OSA and/or narcolepsy. Initiation of solriamfetol was classified as: (1) de novo (EDS medication-naive); (2) transition (switched/switching from existing EDS medication[s] to solriamfetol), or (3) add-on (adding solriamfetol to current EDS medication[s]). Study fielding occurred 3-19 June 2020. Data were summarized descriptively. RESULTS: Twenty-six physicians participated in the study, of whom 24 provided data from 50 patients with OSA (mean ± standard deviation [SD] age, 51.9 ± 9.1 years; 62% male). Mean apnea-hypopnea index at diagnosis indicated that most patients had severe OSA and 92% were adherent to positive airway pressure therapy. EDS was primarily moderate (56%) or severe (36%). Solriamfetol initiation was de novo for 44% of patients, transition for 52%, and add-on for 4%. Efficacy (including the need for better efficacy) was the primary reason for the initiation of solriamfetol as de novo (82%), transition (58%), and add-on (100%) therapy. Starting doses were predominantly 37.5 mg/day (48%) or 75 mg/day (48%); stable doses were typically 75 mg/day (56%) or 150 mg/day (40%). Most patients (64%) adjusted dosages once, reaching stable doses over a median (range) of 14 (1-74) days. Physicians considered EDS severity (32% of patients) when titrating, but more commonly no specific patient factors caused them to alter their titration (44% of patients). Physicians abruptly discontinued wake-promoting agents (WPAs; 17/18, 94%) and stimulants (6/9, 67%) for transitioning patients. The hypothetical patient scenario showed that physicians discontinuing prior WPAs commonly considered the current dose (23%) and potential adverse events (15%). Most patients (96%) were stable on solriamfetol at data collection. CONCLUSIONS: In a real-world study, most physicians initiated solriamfetol at 37.5 or 75 mg/day and titrated to 75 or 150 mg/day for patients with EDS associated with OSA, adjusted dosages once, and abruptly discontinued prior WPAs. At data collection, most patients remained on solriamfetol.

Clinicopathological characteristics of individuals with coexisting melanoma and chronic lymphocytic leukaemia: a multicentre cohort study.

BACKGROUND: Individuals with a prior diagnosis of chronic lymphocytic leukaemia (CLL) have a higher risk of developing melanoma and exhibit poorer outcomes than patients without CLL. However, there are limited data reporting the clinicopathological features of melanoma diagnosed in patients with CLL. AIMS: To review clinicopathological characteristics of patients with coexisting diagnoses of melanoma and CLL. METHODS: A retrospective review was undertaken for patients with coexisting diagnoses of melanoma and CLL between 2005 and 2015 in 11 centres in the UK and Ireland. RESULTS: Overall, 46 cutaneous melanomas identified in 45 patients were included. In 28 (62.2%) patients, melanoma was diagnosed after an existing diagnosis of CLL. In this group, mean Breslow thickness was 2.7 mm (range 0.2-25 mm). Ten patients (35.7%) developed locoregional recurrence and 8 (28.6%) developed distant metastases. Melanoma-specific mortality was 5 of 28 (17.9%) and all-cause mortality was 13 of 28 (46.4%). In 17 patients, melanoma was diagnosed before CLL. In this group, mean BT was 2.9 mm (range 0.4-14 mm); five patients (29.4%) developed locoregional recurrence and three (17.6%) developed distant metastases. Melanoma-specific mortality was 1 of 17 (5.8%) and all-cause mortality was 5 of 17 (29.4%) in this group. CONCLUSIONS: To our knowledge, this is the first and largest cohort study to report clinicopathological data of coexisting melanoma and CLL in the UK and Ireland. Although the thickness of primary melanoma was not different before or after a CLL diagnosis, melanoma recurrence and melanoma-specific mortality appear to be more common in patients with a prior diagnosis of CLL.

A Field Primer for Monitoring Benthic Ecosystems using Structure-from-Motion Photogrammetry.

Structure-from-motion (SfM) photogrammetry is a technique used to generate three-dimensional (3D) reconstructions from a sequence of two-dimensional (2D) images. SfM methods are becoming increasingly popular as a noninvasive way to monitor many systems, including anthropogenic and natural landscapes, geologic structures, and both terrestrial and aquatic ecosystems. Here, a detailed protocol is provided for collecting SfM imagery to generate 3D models of benthic habitats. Additionally, the cost, time efficiency, and output quality of employing a Digital Single Lens Reflex (DSLR) camera versus a less expensive action camera have been compared. A tradeoff between computational time and resolution was observed, with the DSLR camera producing models with more than twice the resolution, but taking approximately 1.4-times longer to produce than the action camera. This primer aims to provide a thorough description of the steps necessary to collect SfM data in benthic habitats for those who are unfamiliar with the technique as well as for those already using similar methods.

A method to estimate pre-exploitation population size.

Antarctic fur seals (Arctocephalus gazella) were commercially exploited on the subantarctic island of South Georgia for over 100 years and nearly driven to extinction. Since the cessation of harvesting, however, their populations have rebounded, and they are now often considered a nuisance species whose impact on the terrestrial landscape should be mitigated. Any evaluation of their current population requires the context provided by their historic, pre-exploitation abundance, lest ecologists fall prey to shifting baseline syndrome in which their perspective on current abundance is compared only with an altered state resulting from past anthropogenic disturbance. Estimating pre-exploitation abundance is critical to defining species recovery and setting recovery targets, both of which are needed for the International Union for the Conservation of Nature's recent efforts to develop a green list of recovering species. To address this issue, we reconstructed the South Georgia fur seal harvest from 1786 to 1908 from ship logbooks and other historical records and interpolated missing harvest data as necessary with a generalized linear model fit to the historical record. Using an approximate Bayesian computation framework, harvest data, and a stochastic age-structured population model, we estimated the pre-exploitation abundance of Antarctic fur seals on South Georgia was 2.5 million females (95% CI 1.5-3.5 million). This estimate is similar to recent abundance estimates, and suggests current populations, and the ecological consequences of so many fur seals on the island, may be similar to conditions prior to human harvest. Although the historic archive on the fur sealing era is unavoidably patchy, the use of archival records is essential for reconstructing the past and, correspondingly, to understanding the present. Article impact statement: Defining species recovery requires an understanding of baseline population state, which can be estimated through statistical methods.

Un Método para Estimar el Tamaño Poblacional Previo a la Explotación Resumen La foca antártica (Arctocephalus gazella) fue explotada comercialmente en la isla subantártica de Georgia del Sur durante más de 100 años y esto casi la llevó a la extinción. Sin embargo, desde que se detuvo la captura de esta especie, su población se ha recuperado y actualmente se le considera con frecuencia una especie molesta cuyo impacto sobre el paisaje terrestre debería ser mitigado. Cualquier evaluación de la población actual requiere del contexto proporcionado por su abundancia histórica previa a la explotación para así evitar que los ecólogos sufran del síndrome de la línea base cambiante, en el cual la perspectiva de la abundancia contemporánea se compara solamente con un estado alterado resultante de perturbaciones antropogénicas pasadas. La estimación de la abundancia previa a la explotación es sumamente importante para definir la recuperación de una especie y para establecer los objetivos de recuperación, ambos requisitos necesarios para los esfuerzos recientes de la Unión Internacional para la Conservación de la Naturaleza (UICN) por desarrollar una lista verde de especies en recuperación. Para tratar este tema reconstruimos la captura de la foca antártica en la isla de Georgia del Sur desde 1786 hasta 1908 a partir de bitácoras de navíos y otros registros históricos e interpolamos los datos faltantes de las capturas conforme fuera necesario con un modelo lineal generalizado que se ajustara al registro histórico. Con un marco de trabajo de cómputo bayesiano aproximado, los datos de las capturas y un modelo poblacional estocástico estructurado por edades estimamos que la abundancia previa a la explotación de la foca antártica en la isla de Georgia del Sur era de 2.5 millones de hembras (95% IC1.5 - 3.5 millones). Este estimado es similar a las estimaciones recientes de abundancia y sugiere que las poblaciones actuales y las consecuencias ecológicas de la presencia de tantas focas en la isla podría ser similar a las condiciones previas a la captura. Aunque el archivo histórico sobre la era de la caza de focas antárticas presenta vacíos inevitablemente, el uso de registros archivados es esencial para la reconstrucción del pasado y, correspondientemente, para entender el presente.

Understanding the role of cutaneous allergy testing in anogenital dermatoses: a retrospective evaluation of contact sensitization in anogenital dermatoses.

BACKGROUND: Patients with anogenital symptoms may delay before seeking medical attention. Attempted self-treatment with multiple topical preparations and excessive hygiene measures offer ideal conditions for sensitization. The aim of this study was to identify the common allergens detected on cutaneous allergy testing in patients presenting with anogenital symptoms. METHODS: A retrospective chart review of patients who underwent cutaneous allergy testing for perianal and/or genital symptoms over a 3-year period, January 2013 to December 2015, n = 99. Information was gathered from medical records, pretesting questionnaires, and cutaneous allergy testing records. RESULTS: At least one relevant allergen(s) was identified in 44/99 (45%) in our cohort, with allergic reactions to fragrances, Myroxylon pereirae, caine mix, sodium metabisulfite, and methylisothiazolinone most frequently observed. CONCLUSIONS: Cutaneous allergy testing is a useful investigation in patients presenting with anogenital symptoms, but advice regarding general skin care measures should not be omitted. The most commonly identified relevant allergens in our study were those present in over-the-counter cleansing and hemorrhoid preparations.

Development and content validity of new patient-reported outcome questionnaires to assess the signs and symptoms and impact of atopic dermatitis: the Atopic Dermatitis Symptom Scale (ADerm-SS) and the Atopic Dermatitis Impact Scale (ADerm-IS).

Objectives: Atopic dermatitis (AD) is a chronic, relapsing skin condition, with signs and symptoms that impact patients' lives and are best measured from the patient perspective. Therefore, there is a need for AD-specific questionnaires that are consistent with Food and Drug Administration guidance and best measurement practices, assessing sign and symptom severity and associated impacts, to support treatment efficacy in regulated trials. The objectives were to develop patient-reported outcome (PRO) questionnaires assessing sign and symptom severity, as well as impacts of moderate-to-severe adult AD. Methods: A targeted literature review and meetings with clinical experts (dermatologists) were conducted to identify AD-related sign, symptom, and impact concepts. Results were harmonized and used to construct two draft PRO questionnaires: the Atopic Dermatitis Symptom Scale (ADerm-SS; 11 items) and the Atopic Dermatitis Impact Scale (ADerm-IS; 10 items). The content validity and questionnaire content were evaluated via qualitative concept elicitation/cognitive debriefing interviews with adult patients with moderate-to-severe AD. Results: From the literature (n = 13 articles), 13 sign and symptom and 43 impact concepts were identified, while 21 sign and symptom and 48 impacts were elicited from experts (n = 3). During the patient interviews (n = 15), 19 sign and symptom and 41 impact concepts were reported, the majority of which were evaluated by the ADerm-SS and ADerm-IS, thus substantiating the content of both questionnaires. Additionally, patients interpreted both questionnaires as intended by the developers. Conclusions: The ADerm-SS and ADerm-IS can be regarded as content-valid PRO questionnaires for moderate-to-severe AD.

The C. difficile puzzle: Putting it all together.

This article explores Clostridium difficile infection (CDI) versus colonization, regulations surrounding CDI reporting, the varied types of CDI testing methods available, and the important role nurses have in thoughtful submission of stool specimens for C. difficile testing.

Development of a Symptom-Focused Patient-Reported Outcome Measure for Functional Dyspepsia: The Functional Dyspepsia Symptom Diary (FDSD).

OBJECTIVES: The Functional Dyspepsia Symptom Diary (FDSD) was developed to address the lack of symptom-focused, patient-reported outcome (PRO) measures designed for use in functional dyspepsia (FD) patients and meeting Food and Drug Administration recommendations for PRO instrument development. METHODS: Concept elicitation interviews were conducted with FD participants to identify symptoms important and relevant to FD patients. A preliminary version of the FDSD was constructed, then completed by FD participants on an electronic device in cognitive interviews to evaluate the readability, comprehensibility, relevance, and comprehensiveness of the FDSD, and to preliminarily evaluate its measurement properties. RESULTS: During concept elicitation interviews, 45 participants spontaneously reported 19 symptom concepts. Of those, seven symptoms were selected for assessment by the eight-item FDSD. Cognitive interviews with 57 participants confirmed that participants were able to comprehend and provide meaningful responses to the FDSD, and that the handheld electronic FDSD format was suitable for use in the target population. Scores of the FDSD were well-distributed among response options, item discrimination indices suggested that the FDSD items differentiate among patients with varying degrees of FD severity, and inter-item correlations suggested that no items of the FDSD were capturing redundant information. Internal consistency estimates (0.87) and construct-related validity estimates using known-groups methods were within acceptable ranges. CONCLUSIONS: The FDSD is a content-valid PRO measure, with preliminary psychometric evidence providing support for the FDSD's items and total score. Further psychometric evaluations are recommended to more fully test the FDSD's score performance and other measurement properties in the target patient population.

Development and initial psychometric evaluation of patient-reported outcome questionnaires to evaluate the symptoms and impact of hidradenitis suppurativa.

BACKGROUND: Two patient-reported outcome (PRO) questionnaires, the Hidradenitis Suppurativa Symptom Assessment (HSSA) and Hidradenitis Suppurativa Impact Assessment (HSIA), were developed to measure signs, symptoms and impacts of HS in treatment efficacy studies. METHODS: In accordance with FDA guidelines and published best practices, four stages of research were conducted to create the questionnaires: concept elicitation, questionnaire construction, content evaluation and psychometric evaluation. RESULTS: Subjects (N = 20) who participated in the concept elicitation stage reported 15 unique HS-related signs and symptoms and 51 impacts. Following this, eight sign and symptom concepts and 21 impacts were selected for construction of the HSSA and HSIA, respectively. During content evaluation, cognitive debriefing interviews with HS subjects (N = 20) confirmed subjects could read, comprehend and meaningfully respond to both questionnaires. Modifications made after this stage of work resulted in a nine-item HSSA and a 17-item HSIA. The HSSA and HSIA were subsequently entered into a US-based observational study (N = 40), and the scores produced by each were found to be reliable, construct valid, and able to distinguish among clinically distinct groups. CONCLUSIONS: The HSSA and HSIA are content-valid, HS-specific, PRO questionnaires with demonstrated ability to generate reliable, valid scores when administered to patients with HS in a research setting.

Psychometric evaluation of the Rheumatoid Arthritis Symptom Questionnaire (RASQ) in an observational study.

OBJECTIVE: To describe the psychometric performance of the scores produced by the Rheumatoid Arthritis Symptom Questionnaire (RASQ), a new patient-reported outcome (PRO) questionnaire developed to assess the signs and symptoms of rheumatoid arthritis (RA). METHODS: Adult subjects with clinically confirmed RA completed a set of questionnaires (including the RASQ) at an initial study visit (Day 1), and then completed the RASQ and the Patient Global Impression of Change (PGI-C) on their own on Day 8. Demographic and health data were summarized using descriptive statistics, and psychometric analyses were conducted, including: acceptability, item and scale distribution, reliability (internal consistency and test-re-test reliability), and construct-related validity (convergent validity and known-groups methods). RESULTS: In total, 200 subjects (females = 61.5%; white = 72.0%; and age [mean] = 60.7 years) with RA were recruited across the US and included in the analysis. There were no missing data recorded for the RASQ, and scores were well distributed for both timepoints. The RASQ Total Symptom Score surpassed the threshold (α ≥ 0.70) for internal consistency at Day 1 (α = 0.967) and test-re-test score reliability (intra-class correlation coefficient [ICC] > 0.70) (ICC = 0.960). Convergent validity analyses demonstrated that the RASQ items and Total Symptom Score had high correlations (convergent validity) with other PRO questionnaires. Known-groups methods demonstrated that the RASQ (Total Symptom Score and all single items) can differentiate between clinically distinct groups. CONCLUSIONS: The RASQ is capable of producing psychometrically sound scores when administered to adults with RA.

The Implications of Recent Recommendations for Managing Patients with Psoriasis Treated with Fumaric Acid Esters.

BACKGROUND/AIMS: Fumaric acid esters (FAEs) are a well-established efficacious systemic treatment for psoriasis. Recent recommendations from the European Medicines Agency suggest monitoring of full blood count every 4 weeks for the duration of therapy for psoriasis. The aim of our study was to assess the incidence of lymphopenia in patients taking FAEs and the impact of recent recommendations for our practice. METHODS: We reviewed 151 patients treated with FAEs for psoriasis between December 2013 and 2015. RESULTS: Lymphopenia <700 × 109/L was detected within the last 12 months in 36/151 (24%) and lymphopenia <500 × 109/L in 10/151 (7%). Of 39 patients no longer on treatment, 7 (18%) stopped because of persistent lymphopenia. CONCLUSION: The implementation of these recommendations would have significant resource implications and also likely influence the acceptability of FAEs to patients. Cessation of FAEs necessitates the need for alternative therapy, commonly biologic therapy.

Development and psychometric evaluation of the self-assessment of psoriasis symptoms (SAPS) - clinical trial and the SAPS - real world patient-reported outcomes.

OBJECTIVE: The Self-Assessment of Psoriasis Symptoms - Clinical Trials (SAPS-CT) and SAPS - Real World (SAPS-RW) were simultaneously created to assess the experience of plaque psoriasis in two unique contexts. METHODS: Qualitative and quantitative research was conducted in four phases namely concept elicitation, questionnaire construction, content evaluation and psychometric evaluation. RESULTS: Following concept elicitation, 18 concepts were selected to inform questionnaire construction of the SAPS-CT and SAPS-RW. To accommodate each context of use, the SAPS-CT asks respondents to rate the target symptom 'at its worst' in the 24 h prior to assessment, while the SAPS-RW asks respondents to rate the target symptom "on average" in the 7 days prior to assessment. Cognitive debriefing confirmed that patients could comprehend and provide meaningful responses to both versions and, after minor modifications, resulted in 11-item questionnaires administered in an observational study (N = 200). Results from the observational study informed further item reduction (SAPS-RW to six items and SAPS-CT to nine items) and demonstrated that scores from each were reliable (Cronbach's α > 0.90, test-retest intraclass correlation coefficient >0.70), construct valid and able to differentiate among clinically distinct groups. CONCLUSION: The SAPS-CT and SAPS-RW are content-valid PRO questionnaires capable of producing psychometrically sound scores when administered chronic to plaque psoriasis patients.

The quality and effectiveness of interventions that target multiple risk factors among young people: a systematic review.

OBJECTIVE: To identify evaluations of interventions that target multiple risk factors in high-risk young people, describe their characteristics, critique their methodological quality and summarise their effectiveness. METHODS: A search of the literature published between 2009 and 2014 identified 13 evaluations of interventions that targeted multiple risk factors, compared to 95 evaluations that targeted single risk factors. The methodological adequacy of the 13 evaluation studies was analysed using the Quality Assessment Tool for Quantitative Studies and information regarding characteristics and intervention effectiveness was extracted and summarised. RESULTS: There were very few outcome evaluation studies of interventions that targeted multiple risk factors, relative to single risk factors, among high-risk young people. Of the identified studies, half were methodologically weak. Interventions delivered in community settings targeted a greater number of risk factors, while those delivered in a school or health setting reported a higher proportion of statistically significant outcomes. No economic analyses were conducted. Conclusions and Implications for Public Health: More methodologically rigorous evaluations of interventions targeting multiple risk factors among high-risk young people are required, especially for those delivered in community settings. Four key areas for improvement are: i) more precisely defining the risk factors experienced by high-risk young people; ii) achieving greater consistency across interventions; iii) standardising outcome measures; and iv) conducting economic analyses.

Patient-Reported Outcomes in Oncology Drug Labeling in the United States: A Framework for Navigating Early Challenges.

BACKGROUND: Despite an increased use of patient-reported outcomes (PROs) in oncology clinical trials, integrating the patient perspective into drug approval decisions and documentation has been challenging. OBJECTIVES: To review important regulatory and measurement terminology, and to provide oncology outcomes researchers and those involved with building oncology programs with tools to plan PRO data collection, particularly in relation to drug efficacy claims for drug labeling in the United States. DISCUSSION: When contemplating a PRO measurement strategy for oncology clinical trials, outcomes researchers are challenged in several ways. First, given multiple stakeholders, researchers must communicate with their scientific, commercial, and regulatory colleagues using often misunderstood terms, such as "label," "claim," "end point," "outcome," and "concept." Second, because stakeholders do not always have access to data from early-stage clinical trials and do not contribute to the target drug's profile in early development, researchers are often unable to address the most important question in building a measurement strategy: What do we want to say about our drug? To overcome these challenges, researchers can systematically develop an end point model to facilitate communication among drug development stakeholders using a common language and to link the building blocks of a PRO measurement strategy, including claims, concepts, questionnaires, and end points. We developed a model that characterizes a disease by its proximal signs and/or symptoms and increasingly distal health outcomes to provide researchers potential measurement concepts that can be instrumental in selecting PRO questionnaires for use in studies. CONCLUSION: PRO data collected in clinical trials should be used in drug development to evaluate the drug's efficacy; it is encouraging that US regulators are willing to work with drug sponsors to overcome the challenges associated with the development, implementation, and interpretation of PROs. The tools discussed in this article can facilitate the planning process for oncology researchers, as well as assist in communicating with US regulators.