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Abstract Background Time-to-event analysis is associated with methodological complexities. Previous research identified flaws in the reporting of time-to-event analyses in randomized trial publications. These hardships impose challenges for meta-analyses of time-to-event outcomes based on aggregate data. We examined the characteristics, reporting and methods of systematic reviews including such analyses. Methods Through a systematic search (02/2017-08/2020), we identified 50 Cochrane Reviews with ≥ 1 meta-analysis based on the hazard ratio (HR) and a corresponding random sample (n = 50) from core clinical journals (Medline; 08/02/2021). Data was extracted in duplicate and included outcome definitions, general and time-to-event specific methods and handling of time-to-event relevant trial characteristics. Results The included reviews analyzed 217 time-to-event outcomes (Median: 2; IQR 1–2), most frequently overall survival (41%). Outcome definitions were provided for less than half of time-to-event outcomes (48%). Few reviews specified general methods, e.g., included analysis types (intention-to-treat, per protocol) (35%) and adjustment of effect estimates (12%). Sources that review authors used for retrieval of time-to-event summary data from publications varied substantially. Most frequently reported were direct inclusion of HRs (64%) and reference to established guidance without further specification (46%). Study characteristics important to time-to-event analysis, such as variable follow-up, informative censoring or proportional hazards, were rarely reported. If presented, complementary absolute effect estimates calculated based on the pooled HR were incorrectly calculated (14%) or correct but falsely labeled (11%) in several reviews. Conclusions Our findings indicate that limitations in reporting of trial time-to-event analyses translate to the review level as well. Inconsistent reporting of meta-analyses of time-to-event outcomes necessitates additional reporting standards.

BackgroundLymphoma treatment can lead to long-term consequences such as fatigue, infertility and organ damage. In clinical trials, survival outcomes, clinical response and toxicity are extensively reported while the assessment of treatment on quality of life (QoL) and symptoms is often lacking.ObjectiveWe evaluated the use and frequency of patient-reported outcome (PRO) instruments used in randomized controlled trials (RCTs) for Hodgkin lymphoma (HL) and their consistency of reporting.MethodsMEDLINE, CENTRAL and trial registries for RCTs investigating HL were systematically searched from 01/01/2016 to 31/05/2022. Following trial selection, trial, patient characteristics and outcome data on the use of PRO measures (PROMs) and reporting of PROs using a pre-defined extraction form were extracted. To assess reporting consistency, trial registries, protocols and publications were compared.ResultsWe identified 4,222 records. Following screening, a total of 317 reports were eligible for full-text evaluation. One hundred sixty-six reports of 51 ongoing/completed trials were included, of which 41% of trials were completed and 49% were ongoing based on registry entries. Full-text or abstract were available for 33 trials. Seventy percent of trials were conducted in the newly diagnosed disease setting, the majority with advanced HL. In 32 trials with published follow-up data, the median follow-up was 5.2 years. Eighteen (35%) completed/ongoing trials had mentioned PRO assessment in registry entries, protocol or publications. Twelve trials (67%) had published results and only 6 trials (50%) reported on PROs in part with the exception of 1 trial where PROs were evaluated as secondary/exploratory outcome. The most referenced global PROM was the EORTC-QLQ-C30 (12 studies), the EQ-5D (3 studies) and the FACT-Neurotoxicity (3 studies). FACT-Lymphoma, a disease-specific PROM for non-HL was mentioned in one ongoing trial. None of the trials referenced the EORTC QLQ-HL27, another disease-specific PROM developed specifically for HL patient’s QoL assessment.DiscussionsOnly one-third of RCTs in HL report PROs as an outcome and only half present the outcome in subsequent publications, showcasing the underreporting of PROs in trials. Disease-specific PROMs are underutilized in the assessment of QoL in HL patients. Guidance on the assessment of PROs is needed to inform on comprehensive outcomes important to patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=391552, identifier CRD42023391552.