Risk-benefit Assessment Research Articles

Expanding Role of Endogenous Biomarkers for Assessment of Transporter Activity in Drug Development: Current Applications and Future Horizon.

The evaluation of transporter-mediated drug-drug interactions (DDIs) during drug development and post-approval contributes to benefit-risk assessment and helps formulate clinical management strategies. The use of endogenous biomarkers, which are substrates of clinically relevant uptake and efflux transporters, to assess the transporter inhibitory potential of a drug has received widespread attention. Endogenous biomarkers, such as coproporphyrin (CP) I and III, have increased mechanistic understanding of complex DDIs. Other endogenous biomarkers are under evaluation, including, but not limited to, sulfated bile acids and 4-pyridoxic acid (PDA). The role of endogenous biomarkers has expanded beyond facilitating assessment of transporter-mediated DDIs and they have also been used to understand alterations in transporter activity in the setting of organ dysfunction and various disease states. We envision that endogenous biomarker-informed approaches will not only help to formulate a prudent and informed DDI assessment strategy but also facilitate quantitative predictions of changes in drug exposures in specific populations.

Surveillance of adverse events following immunisation in Australia, COVID-19 vaccines, 2021.

This report summarises Australia's spontaneous (passive) surveillance data for adverse events following immunisation (AEFI) for coronavirus disease 2019 (COVID-19) vaccines in 2021 reported to the Therapeutic Goods Administration (TGA). The TGA strongly promoted and facilitated adverse event reporting in preparation for, and during, the COVID-19 vaccine rollout as a core component of the most intensive vaccine safety monitoring ever conducted in Australia. There were 111,348 AEFI reports for COVID-19 vaccines administered in 2021, an annual AEFI reporting rate of 271.4 per 100,000 doses of COVID-19 vaccines administered to people aged ≥ 12 years. The annual AEFI reporting rate for non-COVID-19 vaccines in 2021 was 30.6 per 100,000 doses administered to people of all ages. Overall, the most frequently reported symptoms were headache, adverse events classified as 'gastrointestinal nonspecific symptoms and therapeutic procedures', myalgia, pyrexia and fatigue, which were consistent with common expected adverse events following COVID-19 vaccines used in Australia. The most commonly reported adverse events of special interest were myocarditis and/or pericarditis, followed by thrombosis and thromboembolism, and anaphylaxis. Of all COVID-19 vaccine AEFI reports, 762 (0.7%) included a fatal outcome, of which over 80% were in people aged ≥ 60 years. Thirteen deaths reported in 2021 were assessed as likely to be causally linked to vaccination. This report confirms the value of spontaneous post-marketing vaccine pharmacovigilance, especially in the context of new vaccines using novel vaccine technologies and near whole-of-population pandemic vaccination programs. The most frequently reported AEFI for COVID-19 vaccines were common, mild and temporary (lasting 1 or 2 days), and consistent with clinical trial and active surveillance data. Ongoing safety monitoring detected rare, unexpected conditions, such as myocarditis/pericarditis and thrombosis with thrombocytopenia syndrome (TTS), which were investigated and confirmed as safety signals, resulting in changes to vaccine recommendations and product information. The outcomes of TGA monitoring were published in weekly vaccine safety reports. Overall, COVID-19 vaccine safety monitoring provided critical information on the risks of vaccine related adverse events that enabled decisionmakers to undertake informed risk-benefit assessments.

A Comparison of Clinical Outcomes Between Anterior Cervical Discectomy and Fusion Versus Posterior Cervical Laminoplasty for Multilevel Cervical Myelopathy.

Retrospective Cohort. To compare patient-reported outcomes and surgical outcomes after anterior cervical discectomy and fusion (ACDF) versus cervical laminoplasty for multilevel cervical spondylotic myelopathy. Treatment options for multilevel cervical spondylotic myelopathy include ACDF and cervical laminoplasty. Given that the literature has been mixed regarding the optimal approach, especially in patients without kyphosis, there is a need for additional studies investigating outcomes between ACDF and cervical laminoplasty. A retrospective review was conducted of adult patients undergoing 3 or 4-level surgery. Patients with preoperative kyphosis based on C2-C7 Cobb angles were excluded. The electronic medical record and institutional databases were reviewed for baseline characteristics, surgical outcomes, and patient-reported outcomes. A total of 101 patients who underwent ACDF and 52 patients who underwent laminoplasty were included in the study. The laminoplasty cohort had a higher overall Charlson Comorbidity Index (3.10 ± 1.43 vs 2.39 ± 1.57, P = 0.011). Both groups had a comparable number of levels decompressed, C2-C7 lordosis, and diagnosis of myelopathy versus myeloradiculopathy. Patients who underwent laminoplasty had a longer length of stay (2.04 ± 1.15 vs 1.48 ± 0.70, P = 0.003) but readmission, complication, and revision rates were similar. Both groups had similar improvement in myelopathy scores (∆modified Japanese Orthopedic Association: 1.11 ± 3.09 vs 1.06 ± 3.37, P = 0.639). ACDF had greater improvement in Neck Disability Index (∆Neck Disability Index: -11.66 ± 19.2 vs -1.13 ± 11.2, P < 0.001), neck pain (∆Visual Analog Scale-neck: -2.69 ± 2.78 vs -0.83 ± 2.55, P = 0.003), and arm pain (∆Visual Analog Scale-arm: -2.47 ± 3.15 vs -0.48 ± 3.19, P = 0.010). These findings persisted in multivariate analysis except for Neck Disability Index. ACDF and cervical laminoplasty appear equally efficacious at halting myelopathic progression. However, patients who underwent ACDF had greater improvements in arm pain at 1 year postoperatively. Longitudinal studies evaluating the efficacy of laminoplasty to mitigate adjacent segment disease are indicated to establish a robust risk-benefit assessment for these 2 procedures. III.

Methodological guidelines and publications of benefit–risk assessment for health technology assessment: a scoping review

ObjectivesTo map the available methodological guidelines and documents for conducting and reporting benefit–risk assessment (BRA) during health technologies’ life cycle; and to identify methodological guidelines for BRA that could serve...

Benefit–Risk Assessment in Sport and Recreation: Historical Development and Review of AS ISO 4980:2023

Risk management involves thinking about what could happen if someone is exposed to a hazard and the likelihood of this event. The vast majority of standards relating to risk management were written in the context of Occupational Health and Safety, as well as Work Health and Safety with the aim of eliminating all risks. In 2023 Standards, Australia published AS ISO 4980:2023: `Benefit-risk assessment for sport and recreational facilities, activities and equipment’. This standard provides a tool for applying risk management in the context of sport and recreation. AS ISO 4980:2023 is a departure from the traditional view of risk management standards in that it presents a view of risk that is not limited to viewing risk only as negative, but rather balances positive benefits with negative risks within the sport and recreation industry. This standard is also different in that it is based specifically on risk to sport and recreational users and not to employees and employers. The benefit that risk provides in the context of sports and recreational activities is placed on an equal footing with the traditional method of assessing risk. There is an expectation in sports and recreational activities that the user is making an implicit trade-off between the benefits and the inherent risks of the activity, including the potential for harm. This implied expectation is that exposure to risk can be positive. Positive risk and learning from making mistakes are not restricted to childhood development where graduated challenges are used but extend throughout our entire life. The goal of this paper is to draw public attention to the new and different perspective of risk on which AS ISO 4980:2023 is based and to provide an understanding of the concept of benefit–risk assessment. The implications of viewing non-workplace risk in a balanced way are discussed.

Key Opinion Leaders' Interviews to Inform the Future of Benefit-Risk Planning in the Medical Total Product Life Cycle of Global Pharmaceutical and Medical Device Organizations.

Key opinion leader (KOL) interviews were conducted by the Benefit-Risk Assessment Planning(BRAP) Taskforce to seek expert opinion mainly from industry and regulatory bodies, about the current status and future direction of benefit-risk assessment (BRA) planning in the lifecycle of medical product development. The findings from these interviews are intended to help communication concerning planning for BRA between industry and regulators and shape future guidance. Key opinion leader interviews consisted of 5 questions related to BRA planning, which were administered to volunteers (mainly clinicians and statisticians) within a pool of experienced pharmaceutical and medical device professionals representing academia, industry, regulatory agenciesand a patient group. The interviewees' responses to the 5 questions were summarized. To analyze the qualitative data, a Coding System was developed to label themes arising from the interviews. The key findings from the interviews were summarized into a Master Template. A quantitative analysis based on descriptive statistics was also conducted. Of the 27 interviewees, there were 11 professionals from regulatory agencies, 11 from industry, 4 from academia and 1 from a patient advocacy group. Key findings based on the comments provided by 48% of the interviewees indicated the need of incorporating BRA into other (e.g., existing) processes with the importance of alignment between processes being stressed in the comments provided by 59% of the interviewees. Commencing BRA early in the product lifecycle was emphasized in comments provided by 44% of the interviewees. Among other needs identified were an appropriate contextualization of benefits and risks (based on comments provided by 41% of interviewees) through adoption of an integrated approach with structured support by regulatory agencies and a need for understanding the audience with better communication of benefit-risk (BR) among all stakeholders (based on comments provided by 44% of the interviewees). Almost all comments provided by interviewees (96%) highlighted the importance of utilizing patient experience/preference to guide new product development and BRA. Comments provided by 74% of the interviewees expressed the need to understand patient tolerance for risk and trade-offs, with a majority (78%) of interviewees highlighting how to gather information, and 59% stressing the need for the selection and development of appropriate methodologies as important considerations for enhancing the quality and relevance of the data collected from patients. Interviewees indicated that BRA should commence early in the medical product development and inform decision-making throughout the product lifecycle. Better planning and integration of BRA into existing processes within industry would be valuable. The importance of incorporating the patient voice into BRA and medical product development was emphasized. Other key findings from the KOL interviews included a need for improved communication of BR information, and establishment of methodologies for performing BRA and soliciting patient input.

Multidisciplinary consensus on the use of hydroxychloroquine in patients with systemic lupus erythematosus

BackgroundHydroxychloroquine (HCQ) is the first-line treatment for systemic lupus erythematosus (SLE); however, there is heterogeneity in its clinical use. This consensus aims to bridge the gap in SLE treatment by providing practical and valuable recommendations for health professionals. MethodsThe methodology used is based on a systematic literature review and a nominal group technique (NGT). A ten-member scientific committee formulated eight clinically relevant questions. First, a systematic review was conducted to identify the available evidence, which the scientific committee evaluated to developed recommendations based on their expertise, achieving consensus through NGT. Results1673 titles and abstracts were screened, and 43 studies were included for meeting the inclusion criteria. The scientific committee established 11 recommendations for HCQ use in initiation, maintenance, and monitoring, considering benefits and potential adverse effects of HCQ. Unanimous agreement was achieved on all recommendations. ConclusionsThe available evidence supports HCQ's effectiveness and safety for SLE. Individualized assessment of the initial HCQ dose is important, especially in situations requiring dose reduction or discontinuation. This risk–benefit assessment, specifically focusing on the balance between retinal toxicity and the risk of SLE relapse, should guide decisions regarding medication withdrawal, considering disease activity, risk factors, and HCQ potential benefits. Close monitoring is essential for optimal disease management and minimize potential risks, such as QT prolongation or retinal toxicity.

Patient experience with immuno-oncology-induced cytokine release syndrome: Developing a conceptual model of symptoms and their impacts on patients' lives.

2654 Background: Immuno-oncology (IO) therapy can cause cytokine release syndrome (CRS) events, which are a constellation of co-occurring signs and symptoms that usually present within 24–48 hours after treatment. There is no clinical consensus on the specific sign and symptom profile for IO-induced CRS. The objectives of this study were to better understand the experiences of patients with IO-induced CRS and to use data analysis, clinician insights, and patient interviews to develop a conceptual model to capture CRS symptoms and impacts on patients’ lives. Methods: A targeted literature review was conducted to identify CRS signs and symptoms across IO therapies. Clinician interviews (n=4) further defined clinical signs and symptoms and explored the impacts of CRS events on patients’ lives. An advisory boardof five academic oncologists then commented on this list of clinical signs, symptoms, and impacts. Finally, qualitative concept-elicitation interviews were conducted with US patients (ongoing at abstract submission; expected N=20 by March 2024)to confirm and describe symptom severity and impacts. The final intended patient interview sample will specifically examine symptoms and impacts across subgroups with different CRS severity levels. Results: A total of 35 signs and symptoms were initially identified from the literature review. These were assessed, confirmed, and sorted via clinician interviews, resulting in a refined list of 16 clinical signs and 28 symptoms relevant to IO-induced CRS. Based on inputs from the subsequent clinical advisory board, clinical signs indicative of CRS (such as, hypotension, fever and hypoxia) were confirmed, and a list of symptoms (such as chills, fatigue, nausea and diarrhea) recommended for inclusion in a new instrument suited to capture patient-reported experiences was generated. CRS impacts were also broadly described, emphasizing activities and behaviors affected by reduced energy and motivation levels, symptom-related distress, and the emotional burden of the experience. Ongoing patient interviews will confirm the importance of these identified CRS symptoms and provide more specific descriptions of the impacts of IO-induced CRS events on peoples’ lives. Conclusions: Key symptoms affecting patients’ daily activities included, but were not limited to, chills, fatigue, nausea, and diarrhea. These were used to develop a CRS-specific, patient-centered conceptual model that will be refined upon completion of ongoing patient interviews (full results to be presented at ASCO 2024). This research will serve as a framework to build a patient-reported outcome instrument that accurately captures patients’ experiences with CRS and is sensitive to various CRS severity levels. The proposed instrument may aid in evaluating outcomes in clinical trials and support benefit-risk and tolerability assessments.

Substituting red meat with insects in burgers: Estimating the public health impact using risk-benefit assessment

In Western societies, reducing red meat consumption gained prominence due to health, environmental, and animal welfare considerations. We estimated the public health impact of substituting beef with house cricket (Acheta domesticus) in European diets (Denmark, France, and Greece) using the risk-benefit assessment (RBA) methodology, building upon the EFSA-funded NovRBA project. The overall health impact of substituting beef patties with insect powder-containing patties was found to be impacted by the amount of cricket powder incorporated in the patties. While using high amounts of cricket powder in meat substitutes may be safe, it does not inherently offer a healthier dietary option compared to beef. Adjustment of cricket powder levels is needed to yield a positive overall health impact. The main driver of the outcome is sodium, naturally present in substantial amounts in crickets. Moreover, the way that cricket powder is hydrated before being used for the production of patties (ratio of powder to water), influences the results. Our study highlighted that any consideration for dietary substitution should be multidimensional, considering nutritional, microbiological and toxicological aspects, and that the design of new food products in the framework of dietary shifts should consider both health risks and benefits associated with the food.

Exposure-Response Analyses for Belzutifan to Inform Dosing Considerations and Labeling.

Belzutifan (Welireg, Merck & Co., Inc., Rahway, NJ, USA) is an oral, potent hypoxia-inducible factor-2α inhibitor, recently approved in the United States for the treatment of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other VHL disease-associated neoplasms. Safety and efficacy were investigated in two clinical studies: a Phase 1 dose escalation/expansion study in solid tumors and RCC and a Phase 2 study in VHL-RCC. A population pharmacokinetic model was used to estimate belzutifan exposures to facilitate exposure-response (E-R) analyses for efficacy and safety endpoints. Relationships between exposure and efficacy (overall response rate, disease control rate, progression-free survival, best overall tumor size response, and other endpoints), safety outcomes (Grade ≥3 anemia, Grade ≥3 hypoxia, and time to first dose reduction/dose interruption), and pharmacodynamic biomarkers (erythropoietin [EPO] and hemoglobin [Hgb]) were evaluated using various regression techniques and time-to-event analyses. Efficacy E-R was generally flat with non-significant positive trends with exposure. The safety E-R analyses demonstrated a lack of relationship for Grade ≥3 hypoxia and a positive relationship for Grade ≥3 anemia, with incidences also significantly dependent on baseline Hgb. Exposure-dependent reductions in EPO and Hgb were observed. Based on the cumulative benefit-risk assessment in VHL disease-associated neoplasms using E-R, no a priori dose adjustment is recommended for any subpopulation. These analyses supported the benefit-risk profile of belzutifan 120 mg once daily dosing in patients with VHL-RCC for labeling and the overall development program.

Successful Treatment of Multiple Arterial Thrombosis in Premature Infant: Clinical Case

Background. Neonatal thrombosis remains a complex and urgent challenge due to the presence of certain features of the hemostasis system in newborns and the variety of clinical signs. Management approaches are still under consideration, therapeutic experience of thrombolytic therapy (TLT) remains limited and requires benefit-risk assessment. Clinical case description. Clinical case of premature infant with multiple arterial thrombosis diagnosed on the 1st day of life is presented. Modern diagnostic features have allowed to establish the right diagnosis quickly and to start the treatment in time despite the similarities of clinical signs with congenital heart disease. Conclusion. TLT and heparin therapy have saved the child’s life, reversed ischemia, and preserved lower limbs from death. Doctors must perform dynamic monitoring during TLT to diagnose and correct hemorrhagic complications in timely manner.

Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data.

In this commentary, we review clinical data which helps inform individualized benefit-risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.Trial Registration: NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.

Design, Methods, and Participation in Riksmaten Young Children—A Swedish National Dietary Survey

BackgroundNational dietary surveys provide essential data for risk benefit assessments of foods and nutrients, for management and policy development. Physical activity measurement and biomonitoring can provide important complementary data but are less commonly included. ObjectivesThis study aimed to describe the study design and methods of the cross-sectional Swedish national dietary survey Riksmaten Young Children (Riksmaten småbarn), of children aged 9 mo, 18 mo, and 4 y. Participation/dropout rates for the 2 older age groups are also presented. The impact of different recruitment strategies is discussed. MethodsChildren (N = 16,655) were randomly selected from the population register; invitations to guardians were sent by post and where possible, followed up by telephone. Food intake was assessed by a 2-d food diary and/or questionnaire. Height and weight were reported after measurement. Physical activity (accelerometery, 7 d) and stool, blood, and urine samples were assessed in subgroups. ResultsFood consumption data were collected in 1828 children (11% of the invited; 18 mo: n = 1078, and 4 y: n = 750). Of participants also in subgroups, 71% provided physical activity data (n = 1307), 60% stool samples (n = 630), and 51% blood and/or urine samples (n = 593). The study population represented all geographic regions and types of municipalities in Sweden, but participating households had both higher education level and higher income than the target population. Only minor differences were seen in participation rates between recruitment via post and telephone compared with those through post only (12% compared with 10%). Repeated contact attempts were needed for the majority of participants (65%). Despite the low-participation rate, 99% of the participants completed the study once started. ConclusionsAlthough it was a challenge to recruit participants, Riksmaten Young Children provides a substantial amount of information at national level, representative in terms of sex, geography, and family structure. The underrepresentation of households with lower socioeconomic position must be considered when generalizing results.

Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

The application of multi-criteria decision analysis in evaluating the value of drug-oriented intervention: a literature review.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment. Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it. Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were "comparative safety/tolerability" (58 times), "comparative effectiveness/efficacy" (56 times), "comparative patient-perceived health/patient reported outcomes" (37 times), "disease severity" (34 times), and "unmet needs" (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were "cost of intervention" (17 times), "comparative other medical costs" (16 times), and "comparative non-medical costs" (18 times). Out of the 10 criteria (18 times) for assessing innovative value, "a novel pharmacological mechanism" was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, "system capacity and appropriate use of intervention" was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, "political/historical/cultural context" was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. "Swing weighting" and "a direct rating scale" were the most frequently used techniques in included articles. Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

A Survey to Assess the Current Status of Structured Benefit-Risk Assessment in the Global Drug and Medical Device Industry.

This industry survey was conducted to gain insight into the ways structured Benefit-Risk assessment (sBRA) of medical products is approached across drug or medical device developing companies, including frameworks and methods that are currently used and areas where future work is being planned. A survey containing 28 questions covering five key areas of sBRA was set-up and shared with representatives from the participating companies. Each company was asked to complete a single survey response including inputs across the company's multidisciplinary key representatives involved in benefit-risk assessment. Of the 26 participating companies, 21 (81%) are conducting sBRA. Considering these 21 qualitative frameworks were used by almost every company (19, 90%), while only 12 (57%) have used a quantitative method. Many companies have sBRA training (17, 81%), document templates (16,76%), Standard Operating Procedures (SOPs)/checklists (13, 62%), and /or best practice manuals/examples (12,57%) available. Considering all 26 companies Software tools (15, 58%) and BR planning documents (11,42%) were identified as areas into which many companies intend to put effort. The industry survey confirmed a wide usage of sBRA by many companies involved in research and development. Nevertheless, sBRA is evolving and several future opportunities like the implementation of visualization tools were identified by the representatives of the pharmaceutical companies. Finally, challenges like the cross-functional comprehension of the added value of sBRA are still seen.

Updated ESAIC guidelines on postoperative delirium in adults

The updated ESAIC guideline on postoperative delirium (POD) comprises a total of 13 recommendations, including five with the recommendation grade "strong": 1.)The assessment of preoperative POD risk factors, 2.)the optimisation of the preoperative condition, 3.)the discussion of prevention strategies, 4)the implementation of a non-pharmacological multicomponent intervention in patients at risk of POD and 5.)the risk-benefit assessment of the prophylactic administration of dexmedetomidine. The latter applies in particular due to the partly contradictory data situation and different areas of application (cardiac surgery versus non-cardiac surgery patients). Index-based EEG monitoring of the depth of anaesthesia is also recommended, whereby other parameters such as burst suppression and density spectral array should also be included. If non-pharmacological measures fail, POD should be treated with haloperidol. In contrast, the use of benzodiazepines is not recommended.

Benefit-Risk Assessment Based on Number Needed to Treat and Number Needed to Harm: Atogepant vs Calcitonin Gene–Related Peptide Monoclonal Antibodies (P5-12.007)

Benefit-Risk Assessment Based on Number Needed to Treat and Number Needed to Harm: Atogepant vs Calcitonin Gene–Related Peptide Monoclonal Antibodies (P5-12.007)

Integrated assessment of inhalation health risk and economic benefit of improving ambient targeted VOCs in Petrochemical industrial area

AbstractThe Maptaphut industrial area, one of the largest petrochemical complexes in Thailand, is the major cause of the various air pollutants. The larger concern is that a significant volume of air pollution is emitted and that air quality management needs to be improved. This is in part due to a lack of deeper understanding of how anthropogenic emissions are emitted from different sources in this area— especially volatile organic compounds (VOCs). Moreover, it has complicated relationship results of air pollution, disease mechanisms, and health effects. As a result, its available data can only give a rough indication of them. These factors are often assumed to be associated with economic consequences, but assessing the health-related economic losses caused by air pollution remains limited in many ways.Four targeted VOCs were analyzed, including benzene, 1,3-butadiene, 1,2-dichloroethane, and vinyl chloride from industrial and non-industrial sources, namely stacks, flares, storage tanks, wastewater treatment plants, transportation and marketing, fugitive losses, slurry/open equipment/vessel, and on-road mobile emissions. Source apportionment can be conducted using emissions inventory (EI) to establish pollution source databases, the dispersion model, and then imported on the risk model by determining receptors. The AERMOD dispersion model coupled with the IRAP-h view model was used to predict the spatial distribution of the ground-level concentration and analyze the inhalation health risk covering cancer and non-cancer risks— as well as the prioritization of pollutants.The risk assessment results indicated that the highest risk occurred most from 1,3-butadiene for cancer and chronic non-cancer risks contributed to fugitive sources, about 83% and 94%, and most benzenes for acute non-cancer risk contributed to on-road mobile sources, at about 56%.Consequently, the benzene classified as the most important priority depending on its risk results, comprehensive epidemiological studies, and discharge volumes.With the economic benefits assessment, BenMAP-CE was further utilized to estimate the health impacts and economic value of multiple scenarios to facilitate decision-making for benzene reduction. Overall, the 10% rollback policy for benzene concentration, monetized value of about 13.13 billion US dollars for all mortalities, gave the best practical scenario for the most economically viable option based on the B/C (benefit/cost) ratio results in Maptaphut. Ultimately, policymakers need to take additional measures to improve air quality and reduce health impacts while also considering economic benefits, especially benzene reduction.

Quantitative evaluation of the impact of relaxing eligibility criteria on the risk-benefit profile of drugs for lung cancer based on real-world data.

Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high-quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non-small cell lung cancer (NSCLC) protocols in China, on the risk-benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross-dimensional real-world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit-risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.