Using GRADE Evidence to Decision frameworks to support the process of health policy-making

BACKGROUND: Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks are well-known tools that enable guideline panels to structure the process of developing recommendations and making decisions in healthcare and public health. To date, they have not regularly been used for health policy-making. This article aims to illustrate the application of the GRADE EtD frameworks in the process of nutrition-related policy-making for a European country. METHODS: Based on methodological guidance by the GRADE Working Group and the findings of our recently published scoping review, we illustrate the process of moving from evidence to recommendations, by applying the EtD frameworks to a fictitious example. Sugar-sweetened beverage (SSB) taxation based on energy density was chosen as an example application. RESULTS: A fictitious guideline panel was convened by a national nutrition association to develop a population-level recommendation on SSB taxation aiming to reduce the burden of overweight and obesity. Exemplary evidence was summarized for each EtD criterion and conclusions were drawn based on all judgements made in relation to each criterion. As a result of the high priority to reduce the burden of obesity and because of the moderate desirable effects on health outcomes, but considering scarce or varying research evidence for other EtD criteria, the panel made a conditional recommendation for SSB taxation. Decision-makers may opt for conducting a pilot study prior to implementing the policy on a national level. CONCLUSIONS: GRADE EtD frameworks can be used by guideline panels to make the process of developing recommendations in the field of health policy more systematic, transparent and comprehensible

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats

Post-Neoadjuvant Surveillance and Surgery as Needed Compared with Post-Neoadjuvant Surgery on Principle in Multimodal Treatment for Esophageal Cancer: A Scoping Review

Background: A substantial fraction of patients with esophageal cancer show post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients, although surveillance and surgery as needed in case of local recurrence may be a treatment alternative for patients with complete response (CR). Methods: We performed a scoping review to describe key characteristics of relevant clinical studies including adults with non-metastatic esophageal cancer receiving multimodal treatment. Until September 2020, relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library, Science Direct, ClinicalTrials, the German study register, and the WHO registry platform. Results: In total, three completed randomized controlled trials (RCTs, with 468 participants), three planned/ongoing RCTs (with a planned sample size of 752 participants), one non-randomized controlled study (NRS, with 53 participants), ten retrospective cohort studies (with 2228 participants), and one survey on patients’ preferences (with 100 participants) were identified. All studies applied neoadjuvant chemoradiation protocols. None of the studies examined neoadjuvant chemotherapeutic protocols. Studies investigated patient populations with esophageal squamous cell carcinoma, adenocarcinoma, and mixed cohorts. Important outcomes reported were overall, disease-free and local recurrence-free survival. Limitations of the currently available study pool include heterogeneous chemoradiation protocols, a lack of modern neoadjuvant treatment protocols in RCTs, short follow-up times, the use of heterogeneous diagnostic methods, and different definitions of clinical CR. Conclusion: Although post-neoadjuvant surveillance and surgery as needed compared with post-neoadjuvant surgery on principle has been investigated within different study designs, the currently available results are based on a wide variation of diagnostic tools to identify patients with pCR, short follow-up times, small sample sizes, and variations in therapeutic procedures. A thoroughly planned RCT considering the limitations in the currently available literature will be of great importance to provide patients with CR with the best and less harmful treatment

European Respiratory Society clinical practice guidelines: methodological guidance [editorial].

ERS has published official methodological guidance for clinical practice guidelines. ERS recommends this to ensure that state-of-the-art guidelines are developed. https://bit.ly/3xP5SSr

Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

Background: Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are older than 60 years. Despite promising treatment options for younger patients, prognosis for the elderly remains poor and efficacy of available treatment options is limited. Materials and Methods: We conducted a scoping review to identify and summarize the current study pool available evaluating different types and combinations of (immuno) chemotherapy with a special focus on HCT-ASCT in elderly PCNSL. Relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library and ScienceDirect (last search conducted in September 2020). For ongoing studies, we searched ClinicalTrials.gov, the German study register and the WHO registry. Results: In total, we identified six randomized controlled trials (RCT) with 1.346 patients, 26 prospective (with 1.366 patients) and 24 retrospective studies (with 2.629 patients). Of these, only six studies (one completed and one ongoing RCT (with 447 patients), one completed and one ongoing prospective single arm study (with 65 patients), and two retrospective single arm studies (with 122 patients)) evaluated HCT-ASCT. Patient relevant outcomes such as progression-free and overall survival and (neuro-)toxicity were adequately considered across almost all studies. The current study pool is, however, not conclusive in terms of the most effective treatment options for elderly. Main limitations were (very) small sample sizes and heterogeneous patient populations in terms of age ranges (particularly in RCTs) limiting the applicability of the results to the target population (elderly). Conclusions: Although it has been shown that HCT-ASCT is probably a feasible and effective treatment option, this approach has never been investigated within a RCT including a wide range of elderly patients. A RCT comparing conventional (immuno) chemotherapy with HCT-ASCT is crucial to evaluate benefit and harms in an un-biased manner to eventually provide older PCNSL patients with the most effective treatment

Developing a Pan-European Technical Standard for a Comprehensive High-quality Lung Cancer CT Screening Program. An ERS Technical Standard.

UNLABELLED Screening for lung cancer with low radiation dose computed tomography (LDCT) has a strong evidence base. The European Council adopted a recommendation in November 2022 that lung cancer screening be implemented using a stepwise approach. The imperative now is to ensure that implementation follows an evidence-based process that delivers clinical and cost effectiveness. This ERS Taskforce was formed to provide a technical standard for a high-quality lung cancer screening program. METHOD A collaborative group was convened to include members of multiple European societies (see below). Topics were identified during a scoping review and a systematic review of the literature was conducted. Full text was provided to members of the group for each topic. The final document was approved by all members and the ERS Scientific Advisory Committee. RESULTS Ten topics were identified representing key components of a screening program. The action on findings from the LDCT were not included as they are addressed by separate international guidelines (nodule management and clinical management of lung cancer) and by a linked taskforce (incidental findings). Other than smoking cessation, other interventions that are not part of the core screening process were not included (e.g. pulmonary function measurement). Fifty-three statements were produced and areas for further research identified. CONCLUSION This European collaborative group has produced a technical standard that is a timely contribution to implementation of LCS. It will serve as a standard that can be used, as recommended by the European Council, to ensure a high quality and effective program