Post-publication research integrity concerns in randomized clinical trials: A scoping review of the literature.

BACKGROUND: Post-publication handling of integrity concerns in randomized clinical trials (RCTs) is a contentious matter. OBJECTIVES: We undertook a scoping systematic review to map the literature regarding post-publication integrity issues in RCTs. SEARCH STRATEGY AND SELECTION CRITERIA: Following prospective registration (https://osf.io/pgxd8) we initially searched PubMed and Scopus but subsequently extended it to include the Cochrane Library, and Google Scholar databases without language, article type or publication time restriction until November 2022. Reviewers independently selected published articles covering any aspect of post-publication research integrity concerns in RCTs. DATA COLLECTION AND ANALYSIS: The study findings grouped within domains relating to issues concerning post-publication integrity were extracted in duplicate, verified by a third reviewer, and then tabulated. MAIN RESULTS: The initial search captured 3159 citations, of which 89 studies were included in the review. Cross-sectional studies constituted the majority of included studies (n = 34, 38.2%), followed by systematic reviews (n = 10, 11.2%), methodology reviews/studies (n = 9, 10.1%) and other types of descriptive studies (n = 8, 9.0%). A total of 21 articles (23.6%) covered the domain on general issues, 25 (28.1%) in the journal's instructions and policies domain, eight (9.0%) in the editorial and peer review domain, one (1.1%) in the correspondence and complaints (post-publication peer review) domain, 12 (13.5%) in the investigation for concerns domain, six (6.7%) in the post-investigation decisions and sanctions domain, none in the critical appraisal guidance domain, five (5.6%) in the integrity assessment in systematic reviews domain, and 26 (29.2%) in the recommendations for future research domain. A total of 12 of the selected articles (13.5%) covered two (n = 9) or three (n = 3) different domains. CONCLUSIONS: Various research integrity domains and issues covering post-publication aspects of RCT integrity were captured and gaps were identified, mostly related with the necessary implications for all stakeholders to improve research transparency. There is an urgent need for a multistakeholder consensus towards creating specific statements for addressing post-publication integrity concerns in RCTs.

Integrity of randomized clinical trials: Performance of integrity tests and checklists requires assessment.

The integrity of randomized clinical trials (RCT) has become a concern owing to a recent rise in the number of retractions and the repercussions this has for evidence-based patient care. However, there is little research on the subject of RCT integrity assessment. Recent literature reviews have revealed that journals' authors' instructions concerning integrity and their investigation policies concerning allegations of misconduct are heterogeneous. The judicious use of integrity tests applied to RCT manuscripts is hampered by an absence of data concerning misconduct prevalence (pre-test probability), a failure to evaluate test performance (validity) and a lack of consensus over a gold standard (against which test accuracy can be evaluated). These deficiencies hinder the post-publication correction of RCT records, the integrity evaluations in systematic reviews of RCTs and the prospective application of preventive solutions in RCT peer-review and preprint assessment. Dealing with the current controversy about trustworthiness of RCT evidence requires a strong investment in research, reform and education concerning research integrity. The purpose of this review article is to highlight the current limitations in dealing with trial integrity-related concerns and to propose solutions to some of these issues.

Research integrity in randomized clinical trials: A scoping umbrella review.

BACKGROUND: Randomized clinical trials (RCTs) are experiencing a crisis of confidence in their trustworthiness. Although a comprehensive literature search yielded several reviews on RCT integrity, an overarching overview is lacking. OBJECTIVES: The authors undertook a scoping umbrella review of the research integrity literature concerning RCTs. SEARCH STRATEGY AND SELECTION CRITERIA: Following prospective registration (https://osf.io/3ursn), two reviewers independently searched PubMed, Scopus, The Cochrane Library, and Google Scholar, without language or time restrictions, until November 2021. The authors included systematic reviews covering any aspect of research integrity throughout the RCT lifecycle. DATA COLLECTION AND ANALYSIS: The authors assessed methodological quality using a modified AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) tool and collated the main findings. MAIN RESULTS: A total of 55 relevant reviews, summarizing 6001 studies (median per review, 63; range, 8-1106) from 1964 to 2021, had an overall critically low quality of 96% (53 reviews). Topics covered included general aspects (15%), design and approval (22%), conduct and monitoring (11%), reporting (38%), postpublication concerns (2%), and future research (13%). The most common integrity issues covered were ethics (18%) and transparency (18%). CONCLUSIONS: Low-quality reviews identified various integrity issues across the RCT lifecycle, emphasizing the importance of high ethical standards and professionalism while highlighting gaps in the integrity landscape. Multistakeholder consensus is needed to develop specific RCT integrity standards.

Health technology assessment of surgical therapies for benign gynaecological disease.

This chapter summarises the evidence of the benefits and harm of surgical therapies for benign gynaecological disease. We have limited the discussion in this chapter to three gynaecological conditions - menorrhagia, endometriosis and benign ovarian tumours - with a further section on the different surgical approaches for performing a hysterectomy for menorrhagia due to dysfunctional uterine bleeding and pelvic masses such as fibroids and benign adnexal masses. The currently available evidence suggests that there is little to choose between the four first-generation endometrial destruction techniques - laser ablation, transcervical resection of endometrium, vaporisation ablation and rollerball ablation - in terms of clinical efficacy and patient satisfaction. There is a paucity of evidence with regards to the comparison of the different second-generation endometrial-destruction techniques but current evidence suggests that bipolar radiofrequency ablation is more effective than thermal balloon ablation for treating menorrhagia. Overall, the second-generation techniques are at least as effective as first-generation methods but are easier to perform and can be done under local rather than general anaesthesia in some circumstances. Hysteroscopic endometrial ablation is an alternative to hysterectomy and should be offered to women with menorrhagia because of its high satisfaction rates, shorter operation time, shorter hospital stay, earlier recovery and reduced postoperative complications; hysterectomy remains the surgical option of choice for women with intractable menorrhagia despite repeated endometrial ablations and for those who do not wish under any circumstances to continue to have menstrual bleeding. The combined use of laparoscopic laser ablation, adhesiolysis and uterine nerve ablation has been shown to have a beneficial effect on pelvic pain associated with mild to moderate endometriosis. Current evidence also supports the use of laparoscopic treatment of minimal and mild endometriosis to improve the on-going pregnancy and live birth rate in infertile patients. The current available evidence suggests that the laparoscopic approach is superior to laparotomy for the surgical management of benign ovarian cysts. It results in less postoperative pain and a shorter postoperative hospital stay; it also costs less. With regards to the surgical approach for performing a hysterectomy for menorrhagia and benign pelvic masses, vaginal hysterectomy should be performed over laparoscopic and abdominal hysterectomy when possible. Where it is not possible to perform the hysterectomy vaginally, then laparoscopic hysterectomy can be employed instead of abdominal hysterectomy to avoid a laparotomy scar. There appears to be no significant advantage in performing a subtotal hysterectomy instead of the total removal of the uterine corpus and cervix.

The Walker Project: a longitudinal study of 48,000 children born 1952-1966 (aged 36-50 years in 2002) and their families.

The Walker cohort is a database of over 48,000 birth records that has recently become available. It contains meticulously recorded details of pregnancy, labour, birth and care before discharge for babies born in hospital in Dundee, Scotland between 1952 and 1966. These babies accounted for 75% of all births in Dundee at this time. Over 34,000 (73%) of these subjects can be identified and this presents the opportunity to link this birth information with a large number of current health-outcome databases covering both primary and secondary care. Further, it allows linkage of records across siblings and over two and, in future, three generations. The number of birth records available and linkage to current databases make this a unique birth cohort with huge potential for the investigation of the fetal origins of adult disease.

Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis.

Our aim was to determine the diagnostic accuracy of endometrial thickness measurement by pelvic ultrasonography for predicting endometrial carcinoma and disease (hyperplasia and/or carcinoma) during an investigation of postmenopausal bleeding. We performed a systematic quantitative review of the available published literature, which consisted of online searching the MEDLINE and EMBASE databases (1966-2000) coupled with scanning of bibliography of known primary and review articles. The selection of studies, assessment of study quality, and extraction of data were performed in duplicate under masked conditions. Included in the analyses were 57 studies with 9031 patients. Accuracy data were summarized using likelihood ratios for various cut-off levels of abnormal endometrial thickness. The commonest cut-offs were 4 mm (9 studies) and 5 mm (21 studies), measuring both endometrial layers. None of the nine studies using the < or = 4 mm cut-off level were of good quality. Only four studies (out of the 21) used the < or = 5 mm cut-off level, which employed the best-quality criteria. Using the pooled estimates from these four studies only, a positive test result raised the probability of carcinoma from 14.0% (95% CI 13.3-14.7) to 31.3% (95% CI 26.1-36.3), while a negative test reduced it to 2.5% (95% CI 0.9-6.4). In conclusion, ultrasound measurement of endometrial thickness alone, using the best-quality studies cannot be used to accurately rule. However, a negative result at < or = 5 mm cut-off level measuring both endometrial layers in the presence of endometrial pathology rules out endometrial pathology with good certainty.