The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation

ObjectiveThe use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation.MethodsThe AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement.ResultsThe expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively.ConclusionsAchieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.     

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

Review of a forensic pseudoscience: Identification of criminals from bitemark patterns

The forensic sciences are a combination of laboratory procedures and physical comparisons of objects associated with victims, perpetrators, and crime scenes. The former is largely university-based protocols adopted by crime labs. The latter is predominantly pattern-matching tools originally developed by police examiners or experts deemed by courts to be relevant to forensic matters. These Court accepted experts bring their reasoning and conclusions into the legal arena. This subgroup of forensics has undergone significant scrutiny in regards to its history of exaggerated claims and weak scientific foundations. This paper addresses the rise and fall of bitemark pattern analysis (i.e. “matching” bitemarks in human flesh to human teeth) in the environment of opposing interests and agendas.     

WFSBP guidelines on how to grade treatment evidence for clinical guideline development

Objective and methods: This paper reviews sources of data typically used in guideline development, available grading systems, their pros and cons, and the methods for evaluating risks of bias in publications, and proposes a revised method for grading evidence and recommendations for use in development of clinical treatment guidelines.

Results: The new World Federation of Societies of Biological Psychiatry (WFSBP) grading system allows guideline developers to follow a multi-step approach of defining levels of evidence, applying criteria for grading (define the acceptability) and the grading of recommendations.

Conclusions: Further, these updated WFSBP recommendations for rating evidence and treatment recommendations provide a grading system that takes into account potential biases in sources of evidence in arriving at final ratings that are likely more clinically meaningful and pragmatic and thus should be used for the development of future treatment guidelines.     

T-DM1 Efficacy in Patients With HER2-positive Metastatic Breast Cancer Progressing After a Taxane Plus Pertuzumab and Trastuzumab: An Italian Multicenter Observational Study

BackgroundT-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2⁺) breast cancer progressing on prior trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy.Patients and MethodsEligible patients were identified within the Gruppo Italiano Mammella (GIM) 14/BIOMETA study, a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT02284581). We searched for patients who received second-line T-DM1 after taxane plus trastuzumab and pertuzumab between November 15, 2013 and May 31, 2018. We calculated median PFS, median time to treatment failure (TTF), prolonged duration of therapy (PDT), objective response rate (ORR), and 1-year OS.ResultsOf 445 patients with HER2⁺ metastatic breast cancer, 77 were eligible for the analysis. At a median follow-up of 7 months, median PFS was 6.3 months (95% confidence intervals [CI], 4.8-7.7 months), and median TTF was 6.2 months (95% CI, 4-8.6 months). More than one-third of patients (37.6%; n = 29) experienced PDT with an ORR of 27.1%. At data cutoff, the median OS was not reached, and the 1-year OS was 82%.ConclusionsOur results show meaningful activity of T-DM1 after front-line pertuzumab plus trastuzumab and a taxane, with about 27% of patients having an objective response and 40% of patients achieving durable disease control.