A Tutorial on Net Benefit Regression for Real-World Cost-Effectiveness Analysis Using Censored Data from Randomized or Observational Studies.

HIGHLIGHTS: We illustrate the steps involved in carrying out cost-effectiveness analysis using net benefit regressions with possibly censored demo data by providing step-by-step guidance and code applied to a data set.We demonstrate the importance of these new methods by illustrating how naïve methods for handling censoring can lead to biased cost-effectiveness results.

EORTC 1409 GITCG/ESSO 01 - A prospective colorectal liver metastasis database for borderline or initially unresectable diseases (CLIMB): Lessons learnt from real life. From paradigm to unmet need.

AIM: Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated. MATERIAL AND METHODS: A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. RESULTS: Perioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1-64.6%), 64.0% (95% CI: 42.5-82%), and 100% (95% CI: 59-100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. CONCLUSION: Across nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database.

An open-label, non-randomized study investigating the safety and efficacy of smallpox vaccine, LC16, as post-exposure prophylaxis for mpox.

Mpox is an acute exanthematous disease caused by the monkeypox virus. Since May 2022, it has spread as a community-acquired infection, mainly in Europe and the United States, and urgent measures to prevent this infection were also required in Japan. In this study, we investigated the post-exposure prophylaxis of mpox and safety after inoculating the smallpox vaccine. Participants in close contact with patients with mpox were inoculated with "Freeze-dried cell culture Smallpox Vaccine LC16," within 14 days after close contact. Six cases were registered, and all the participants were inoculated. No mpox symptoms or related complications were observed in the participants for 21 days after the close contact. Adverse events due to inoculation, such as rash, fever, lymphadenopathy, and local reaction at the inoculation site (comprising erythema, swelling, induration, and pain) were observed in the participants; however, all inoculation-related events were non-severe and non-serious, and the participants recovered during the 28-day observation period. The findings of this study suggest that inoculation with LC16 is an effective post-exposure prophylaxis in individuals who had close contact with patients with mpox. Further large-scale studies are warranted to validate these findings.

Proton versus photon radiation therapy: A clinical review.

While proton radiation therapy offers substantially better dose distribution characteristics than photon radiation therapy in certain clinical applications, data demonstrating a quantifiable clinical advantage is still needed for many treatment sites. Unfortunately, the number of patients treated with proton radiation therapy is still comparatively small, in some part due to the lack of evidence of clear benefits over lower-cost photon-based treatments. This review is designed to present the comparative clinical outcomes between proton and photon therapies, and to provide an overview of the current state of knowledge regarding the effectiveness of proton radiation therapy.

Can Non-Randomised Studies of Interventions Provide Unbiased Effect Estimates? A Systematic Review of Internal Replication Studies.

Non-randomized studies of intervention effects (NRS), also called quasi-experiments, provide useful decision support about development impacts. However, the assumptions underpinning them are usually untestable, their verification resting on empirical replication. The internal replication study aims to do this by comparing results from a causal benchmark study, usually a randomized controlled trial (RCT), with those from an NRS conducted at the same time in the sampled population. We aimed to determine the credibility and generalizability of findings in internal replication studies in development economics, through a systematic review and meta-analysis. We systematically searched for internal replication studies of RCTs conducted on socioeconomic interventions in low- and middle-income countries. We critically appraised the benchmark randomized studies, using an adapted tool. We extracted and statistically synthesized empirical measures of bias. We included 600 estimates of correspondence between NRS and benchmark RCTs. All internal replication studies were found to have at least "some concerns" about bias and some had high risk of bias. We found that study designs with selection on unobservables, in particular regression discontinuity, on average produced absolute standardized bias estimates that were approximately zero, that is, equivalent to the estimates produced by RCTs. But study conduct also mattered. For example, matching using pre-tests and nearest neighbor algorithms corresponded more closely to the benchmarks. The findings from this systematic review confirm that NRS can produce unbiased estimates. Authors of internal replication studies should publish pre-analysis protocols to enhance their credibility.

The design and analysis of non-randomized studies: a case study of off-label use of hydroxychloroquine in the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted researchers to conduct non-randomized studies in an effort to find an off-label drug that can effectively combat the virus and its effects. While these studies can expedite the drug approval process, researchers must carefully design and analyze such studies in order to perform rigorous science that is reproducible and credible. This article focuses on several key design and analysis considerations that can improve the scientific rigor of non-randomized studies of off-label drugs. Areas covered: The aim of this article is to provide an overview of best approaches that should be considered for non-randomized studies on off-label drugs. We discuss these approaches in detail and use a non-randomized study by Rivera et al. in Cancer Discovery as an example of methods that have been undertaken for COVID-19. Expert opinion: While non-randomized studies are inherently biased, they may be unavoidable in situations such as the COVID-19 pandemic, where researchers need to find an effective treatment quickly. We believe that a well-formed experimental design, high-quality data collection, and a well-thought-out statistical and data analysis plan are sufficient to produce rigorous and credible results for making an optimal decision.

Digital health interventions to help living with cancer: A systematic review of participants' engagement and psychosocial effects.

OBJECTIVE: Digital health interventions (DI) open the possibility for cancer patients and survivors to manage the disease and its side effects when they return home after treatment. This study aims to highlight the components of DI, investigate patient engagement with DI, and explore the effects of DI on psychosocial variables. METHODS: In September 2017, we performed a systematic review of studies focusing on DI which target cancer patients or survivors. RESULTS: A total of 29 articles (24 studies) were reviewed. There was considerable heterogeneity in study methods, in outcome definitions, in measures for engagement with DI and in psychosocial variables assessed. Results from the studies showed a high level of engagement. Self-efficacy, psychological symptoms, and quality of life were the most commonly assessed psychosocial variables. However, results for the effect of DI on psychosocial variables were inconsistent. Regarding pain management, results were in line with what one would expect. CONCLUSIONS: The present review showed that despite the heterogeneity in the studies assessed and inconsistent results, DI may constitute an excellent means to help cancer patients and survivors cope better with the disease and with treatment side effects, as they can improve self-management and wellbeing. In order to acquire a greater understanding of the mechanisms underlying cancer patients'/survivors' psychological and behavioral changes in terms of adopting DI, direct comparison between studies is needed. However, this can only come about if methodological and conceptual standardization of DI is implemented.

Pautas de chequeo, parte I: consort y trend / Cheklists, part I: consort and trend

One of the most common problems in scientific articles is its poor reporting, a situation that leads to lack of information, affecting internal and external validity, questioning his contribution and usefulness. This has been studied leading to propositions by the international scientific community, reflected in a series of guidelines or checklists as CONSORT and TREND for randomized clinical trials (RCTs) and non-randomized intervention studies (NRISs) respectively. The CONSORT checklist was created in 1996, with a final version in 2010, consisting of 25 items, grouped into 6 domains: Title and Summary, Introduction, Methods, Results, Discussion, and Other information; representing the critical points in a RCT report. In many cases RCTs are no feasible so other research designs such as NRISs has to be executed, for this design the TREND checklist was developed in 2004, consisting of 22 items, grouped into 5 domains: Title and Summary, Introduction, Methods, Results and Discussion. Even when the evidence has been contradictory regarding the impact of these checklists, they represent an important tool to improve biomedical research. This article tries to explain these checklists and encourage its use by the authors of the Revista Chilena de Cirugía, in function to contribute to continuous improvement of their articles in a simple and efficient way.

Uno de los problemas más frecuentes en los artículos científicos es su deficiente reporte, situación que redunda en falta de información, afectando la validez interna y externa, cuestionando su aporte y utilidad. Esta situación ha sido motivo de estudio y propuestas por parte de la comunidad científica internacional, que se materializan en una serie de pautas de chequeo o checklists como CONSORT y TREND para ensayos clínicos aleatorizados (ECA) y estudios de intervención no aleatorizados (EINA) respectivamente. La propuesta CONSORT nace en 1996, con una última versión en 2010, constituida por 25 ítems, agrupados en 6 dominios: Título y Resumen, Introducción, Metodología, Resultados, Discusión y Otra información; representando puntos esenciales a reportar en un ECA. En muchas ocasiones se debe recurrir a otro tipo de diseños de investigación como los EINA, para los que en 2004 se desarrolló la pauta TREND, el cual consta de 22 ítems, agrupados en 5 dominios: Título y resumen, Introducción, Métodos, Resultados y Discusión. Aun cuando la evidencia ha sido contradictoria respecto al impacto de estas pautas, estas representan una herramienta relevante para mejorar la investigación biomédica. El presente artículo intenta dar a conocer estos checklists e incentivar su uso por parte de los autores de la Revista Chilena de Cirugía, con lo cual se espera contribuir a una mejora continua de sus artículos de una forma simple y eficiente.