Background There is a growing interest in the inclusion of real-world and observational studies in evidence synthesis such as meta-analysis and network meta-analysis in public health. While this approach offers great epidemiological opportunities, use of such studies often introduce a significant issue of double-counting of participants and databases in a single analysis. Therefore, this study aims to introduce and illustrate the nuances of double-counting of individuals in evidence synthesis including real-world and observational data with a focus on public health. Methods The issues associated with double-counting of individuals in evidence synthesis are highlighted with a number of case studies. Further, double-counting of information in varying scenarios is discussed with potential solutions highlighted. Results Use of studies of real-world data and/or established cohort studies, for example studies evaluating the effectiveness of therapies using health record data, often introduce a significant issue of double-counting of individuals and databases. This refers to the inclusion of the same individuals multiple times in a single analysis. Double-counting can occur in a number of manners, such as, when multiple studies utilise the same database, when there is overlapping timeframes of analysis or common treatment arms across studies. Some common practices to address this include synthesis of data only from peer-reviewed studies, utilising the study that provides the greatest information (e.g. largest, newest, greater outcomes reported) or analysing outcomes at different time points. Conclusions While common practices currently used can mitigate some of the impact of double-counting of participants in evidence synthesis including real-world and observational studies, there is a clear need for methodological and guideline development to address this increasingly significant issue.

IntroductionIt is estimated that peripheral arterial disease occurs in one in five people aged over 60 years in the UK. Major lower limb amputation is a debilitating and life-changing potential outcome of peripheral arterial disease. A number of risk factors are involved in the development of the disease including smoking and diabetes. There is debate over the prevalence of major lower limb amputation in the UK with regional variations unexplained. The choice of data source can affect the epidemiological calculations and sources can also differ in the ability to explain variation. This study will aim to estimate the prevalence/incidence/number of major lower limb amputation in the UK. It will also identify sources of routinely collected electronic health data which report the epidemiology of major lower limb amputation in the UK.Methods and analysisA systematic search of peer-reviewed journals will be conducted in Medline, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature, Allied and Complementary Medicine Database, The Cochrane Library and Scopus. A grey literature search for government and parliament publications, conference abstracts, theses and unpublished articles will be performed. Articles will be screened against the inclusion/exclusion criteria and data extracted using a pretested extraction form by two independent reviewers. Prevalence, incidence or number of cases (depending on data reported) will be extracted. Disagreements will be resolved by discussion. Data synthesis will be performed either as a narrative summary or by meta-analysis. Heterogeneity will be assessed using the I2 statistic. If heterogeneity is low-moderate, pooled estimates will be calculated using random-effects models. If possible, meta-regression for time trends in the incidence of major lower limb amputation will be performed along with subgroup analysis, primarily in regional variation.Ethics and disseminationEthics approval is not required for this study as study data are anonymised and available in the public domain. Dissemination will be by publication in a peer reviewed journal and by appropriate conference presentation.PROSPERO registration numberCRD42020165592

ObjectiveEstimate the prevalence/incidence/number of major lower extremity amputations (MLEAs) in the UK; identify sources of routinely collected electronic health data used; assess time trends and regional variation; and identify reasons for variation in reported incidence/prevalence of MLEA.DesignSystematic review and narrative synthesis.Data sourcesMedline, Embase, EMcare, CINAHL, The Cochrane Library, AMED, Scopus and grey literature sources searched from 1 January 2009 to 1 August 2021.Eligibility criteria for selecting studiesReports that provided population-based statistics, used routinely collected electronic health data, gave a measure of MLEA in adults in the general population or those with diabetes in the UK or constituent countries were included.Data extraction and synthesisData extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Instruments were performed by two reviewers independently. Due to considerable differences in study populations and methodology, data pooling was not possible; data were tabulated and narratively synthesised, and study differences were discussed.ResultsTwenty-seven reports were included. Incidence proportion for the general population ranged from 8.2 to 51.1 per 100 000 and from 70 to 291 per 100 000 for the population with diabetes. Evidence for trends over time was mixed, but there was no evidence of increasing incidence. Reports consistently found regional variation in England with incidence higher in the north. No studies reported prevalence. Differences in database use, MLEA definition, calculation methods and multiple procedure inclusion which, together with identified inaccuracies, may account for the variation in incidence.ConclusionsUK incidence and trends in MLEA remain unclear; estimates vary widely due to differences in methodology and inaccuracies. Reasons for regional variation also remain unexplained and prevalence uninvestigated. International consensus on the definition of MLEA and medical code list is needed. Future research should recommend standards for the reporting of such outcomes and investigate further the potential to use primary care data in MLEA epidemiology.Systematic review registrationPROSPERO CRD42020165592.

Aims: Major lower extremity amputations (MLEAs) are understood to be well recorded in secondary care in England in the Hospital Episode Statistics (HES) database. It is unclear how well MLEAs are recorded in primary care databases. Background: This study compared MLEA event case ascertainment in Clinical Practice Research Datalink (CPRD) to that in HES. Methods: MLEA events were ascertained in CPRD and in HES linkage between 1 January 2010 and 31 December 2019. The number of MLEA events and the number of patients with at least one MLEA in each database were recorded and compared. Individual events were matched between the databases using varying date-matching windows. Reasons for differences in case ascertainment were explored. Findings: In total 23 262 patients had at least one MLEA record, 8716 (37.5%) had an MLEA record in HES only, 5393 (23.2%) in CPRD only and 9153 (39.4%) in both. Out of a total of 75 221 events, 13 071 (62.4%) were recorded in HES only and 44 151 (81.3%) in CPRD only. 7874 (37.6%) of HES events were recorded in CPRD and 10 125 (18.6%) of CPRD events were recorded in HES when using the maximum date matching window of 28 days plus the time between admission and procedure. The main reasons for differences in case ascertainment included, re-recordings and miscoding in CPRD. Compared to HES, MLEAs are poorly recorded in CPRD predominantly due to re-recordings of events and miscoding procedures. CPRD data cannot solely be relied upon to ascertain cases of MLEA; however, HES linkage to CPRD may be useful to obtain medical history of diagnoses, medication and diagnostic tests.