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Epidemiology
Protocol
Epidemiology of major lower limb amputation using routinely collected electronic health data in the UK: a systematic review protocol
  1. Anna Meffen1,
  2. Coral J Pepper2,
  3. Robert D Sayers3,
  4. Laura J Gray1
  1. 1Department of Health Sciences, University of Leicester, Leicester, UK
  2. 2Library and Information Services, University Hospitals of Leicester NHS Trust, Leicester, UK
  3. 3Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
  1. Correspondence to Anna Meffen; am1173{at}le.ac.uk

Abstract

Introduction It 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 analysis A 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 A grey literature search for government and parliament publications, conference abstracts, theses and unpublished articles will be performed.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 dissemination Ethics 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 number

CRD42020165592

  • lower-extremity amputation
  • systematic review
  • peripheral artery disease
  • diabetes
  • routinely collected health data
  • real world evidence
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

http://dx.doi.org/10.1136/bmjopen-2020-037053

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    Strengths and limitations of this study

    • This review will report estimates of the prevalence/incidence/number of major lower limb amputation in the UK and also provide information on the use of routinely collected electronic health data in the epidemiology of major lower limb amputation.

    • The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be adhered to for both the systematic review and the PRISMA-Protocol.

    • A comprehensive search strategy will be employed in both peer-reviewed and grey literature searches.

    • This study only looks at data sources in the UK and as such will only be applicable to use for this population.

    • It is expected that only a small number of studies will be included in this systematic review with large amounts of between study heterogeneity which may be in part down to population and methodological differences.

    Introduction

    Peripheral arterial disease (PAD) is the leading cause of all lower limb amputation where the causes are not due to cancer or trauma.1 PAD occurs when an excess of plaque (atheroma) builds-up in the arteries and restricts blood flow to the limbs. PAD can occur with or without symptoms. The most common symptom of PAD is pain on walking called intermittent claudication.2 If the disease progresses patients may develop pain at rest that may be complicated by ulceration and gangrene, this is critical leg ischaemia and without urgent treatment to improve the blood supply to the leg, amputation will result. The number of people diagnosed with PAD worldwide is estimated to be over 200 million.3 In the UK PAD occurs in 20% of people aged over 60 years.4 The prevalence of amputation in PAD patients is thought to be 3%–4%.5 In the UK the prevalence of symptomatic PAD is decreasing with figures of 2.4% in 2014 compared with 3.4% in 2000.6 This is surprising given the significant increase in diabetes, one of the major risk factors.7 Other key risk factors for PAD include: smoking, age, hypertension and dyslipidaemia.8 There is evidence to suggest that, in England, fewer major lower limb amputation operations are performed than minor.9 10 This may be partly due to the advancement in surgical care including the range and accessibility of revascularisation procedures.11 As PAD can have debilitating and life-changing outcomes, it is imperative that the scale of outcomes such as major lower limb amputation are known and any variation in prevalence explained so that suitable and targeted preventative measures can be put in place.

    Routinely collected electronic health data are a widely used resource for epidemiological studies. Data are collected from primary and secondary care providers, deidentified and stored in a number of different databases. There are many strengths and limitations to using routinely collected health data in epidemiology which need to be taken into account when analysing the data.12 The main positive aspect of using large datasets in research is that it enables more accurate results. One particularly notable, but improving issue when using routinely collected health data for research is that of coding errors.13–15 There is some evidence to suggest that including poor-quality data in incidence studies can affect the apparent trends in incidence.15 Strengths and limitations can vary between databases as they are established for different reasons. For example, the primary objective of the Hospital Episode Statistics (HES)16 database is to collect secondary care data to allow hospitals to be paid for the care they deliver making it a very complete dataset but lacking in some detail. Whereas the primary objective of the Clinical Practice Research datalink (CPRD)17 18 database is to extract routinely collected clinical primary care data from GP practices for research purposes meaning that this dataset contains far more detail than HES, but CPRD does not hold the data from all UK practices and there may be bias in the reporting. Given this, it can be expected that the choice of database used in a study has potential to affect the resulting study outcome.

    Currently, there is confusion and debate about the incidence of major lower limb amputation due to conflicting reports.9 10 19 Moxey et al give an incidence proportion of 5 per 100 000 in the population with no change in the 5-year period between 2003 and 2008,10 whereas Ahmad et al give an incidence proportion of 25 per 100 000 population with proportions dropping by up to 20% over the period between 2003 and 2013.19 It is not clear which databases are more frequently being used in the epidemiological reporting of major lower limb amputations and therefore what impact this might be having on the reporting. Other reasons for variation have been explored. For example, a systematic review by Davies et al found substantial differences in methodology between studies.20 Differences included the denominator population, the definitions of major lower limb amputations, standardisation techniques and subgroups analysed. The heterogeneity of these studies made it too difficult to compare the trends over time. As well as estimating the epidemiology of major lower limb amputation in the UK, this study aims to expand on this by looking more closely at the data sources and identifying which sources are most frequently used and which are under-used and discussing their differences, strengths and limitations.

    Objectives

    1. To ascertain the incidence/prevalence/number of major-lower limb amputation in the UK and any changes over time.

    2. To determine any regional and subgroup differences in the incidence/prevalence/number of major lower limb amputation.

    3. To establish which routinely collected electronic health databases are being used and which are available for use in reporting the epidemiology of major lower limb amputation.

    4. To discuss the strengths and limitations of each database used.

    5. To explain reasons for variation in the reporting of the epidemiology of major lower limb amputation.

    Methods

    The systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting the results of systematic reviews.21

    The PRISMA-Protocol checklist for systematic review protocols was used when writing this protocol. Tabulated versions are included in online supplementary files 1 and 2.22

    Peer-reviewed literature

    The search strategy was developed by a specialist vascular clinical librarian.

    The electronic databases Medline, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature, The Cochrane Library, Allied and complementary medicine Database and Scopus will be searched using combinations of key words and topics. Full-search strategies are included in online supplementary files 3 and 4. The search strategy was developed in Medline and will then be adapted for use in other databases. The search will limit the date of publication to 2009 onwards, to studies published in English and to studies based on UK data, using filters where possible.23 24 Search results will be exported to and stored in EndNote. The reference lists of any studies selected for inclusion will be checked for additional studies to include. Searches will be rerun at the end of the review process to check for any publications in the intervening period.

    Grey literature

    The grey literature websites www.opengrey.eu, openDoar.org, openAire.eu and base-search.net will be searched using the key word ‘amputation’/‘amput*’. Electronic databases aforementioned will be used to search conference papers as well as peer reviewed literature. A thesis search will be performed in eTHOS, on OpenDisserations.org and in the University of Leicester thesis database. Government publications will be searched on www.gov.co.uk and Parliament publications will be searched using www.parliament.uk and www.vvappg.com with searches to include the key words ‘amputation’. Publication searches will also be performed on the health record database websites www.digital.nhs.uk, www.QResearch.org, and the bibliography provided at www.CPRD.com. Experts in the field will also be consulted to further identify articles for inclusion potential.

    Inclusion/exclusion criteria

    Articles considered for inclusion will provide population-based statistics made available since 2009 that use routinely collected electronic health data as their data source, that are written in English and that provide a measure (eg, prevalence/incidence/number) of major lower limb amputation in adults in the general public or in persons diagnosed with diabetes in England or UK. The decision to only consider for inclusion studies published from 2009 onwards was made to ensure that epidemiological calculations are reflective of current trends in the major risk factors. Studies that only include adults (or report a sub group for adults) are more likely to exclude major lower limb amputations that were performed for reasons other than PAD or diabetes, such as cancer and trauma. Studies of adults that include those that have lost limbs due to cancer and trauma may be included in the study but this information will be explicitly stated where available.

    A specific definition of major lower limb amputation will not be used to exclude articles from the review as it is anticipated that the precise definition will vary among studies reporting the epidemiology of major lower limb amputation. There is no apparent, explicit definition of ‘major’ lower limb amputation. For these reasons, a decision was made to include all studies that report for a major lower limb amputation and to extract, tabulate and discuss the differences in definition. Comparisons will also be made between the extracted definitions and the case ascertainment coding of major lower limb amputation. Further comparisons of the definitions will be made to the Global Vascular Guidelines (GVG) where a minor lower limb amputation is defined but a major lower limb amputation is only inferred.25 Some studies may report epidemiology statistics for both minor and major lower limb amputation. Where this occurs, data from minor amputations (ie, below the ankle joint, as per the GVG definition) will be excluded, articles that do not report separate statistics for major lower limb amputation will also be excluded. Only articles with comparable definitions will be considered for data pooling.

    Screening

    The titles, authors, abstracts and the date and location of publication will be extracted and imported into EndNote X9. Duplicates will be removed at this stage. The titles and abstracts will then be screened for inclusion by two reviewers independently. The full texts will then be screened by two reviewers for confirmation of suitability. Any disagreement on suitability for inclusion will be resolved by discussion between the two reviewers and, if necessary, with the aid of the third reviewer. Reasons for exclusion will be noted at each stage.

    Outcomes

    The main outcome will be an estimate of the incidence, prevalence or absolute number of major lower limb amputation in England (UK) depending on the epidemiological statistics available.

    Regional and subgroup measures, any reported trends over time, any standardisation methods used and code lists for the identification of major lower limb amputation in the databases will be analysed where available.

    The routinely collected electronic health data source used in each study will be reported and discussed.

    Data extraction

    After screening has taken place the extraction will be performed by two reviewers using a pretested tabulated extraction form. Disagreement between the two reviewers will be resolved by discussion and, if necessary, by the involvement of the third reviewer.

    Data to be extracted includes:

    • Author, title, publication date and published location.

    • The data sources used in the analysis.

    • Epidemiological measure of major lower limb amputation—prevalence/incidence/number including any CI, SE and variance recorded.

    • Definition of major lower limb amputation.

    • Population studied (England/UK, diabetic/non diabetic, age limits, date limits, comorbidities or reasons for amputation excluded for example, cancer/trauma).

    • Data recorded for any subgroups analysis (eg, sex, age, ethnicity).

    • Any standardisation methods used.

    • Code lists used to identify subjects with major lower limb amputation.

    Corresponding authors will be contacted to attempt to retrieve any data that is missing from the full text and available attachments.

    Quality assessment

    There are many quality assessment tools available but the most applicable to the type of studies and publications to be included in this systematic review are the increasingly used Joanna Briggs Institute (JBI) Critical Appraisal Instrument for Studies Reporting Prevalence Data and, for any cohort studies, the JBI Critical Appraisal Checklist for Cohort Studies.26–30 These tools will be used to critically appraise the quality of the studies that have been selected for inclusion. Following the JBI guidelines, two reviewers will independently carry out the critical appraisal using the critical appraisal tool and discuss the results coming to agreement on the conclusions with the aid of a third reviewer where necessary. The aim of the quality assessment will not be to further exclude studies from the review but instead to discuss the strengths and limitations of the studies.

    Data synthesis

    For the objective of ascertaining the incidence/prevalence/number of major lower limb amputation, where data allow, the statistic will be converted into a consistent measure. Different measures will be pooled independently. The I2 statistic will be calculated to determine the percentage of variation due to heterogeneity. If heterogeneity levels deem it possible then meta-analysis of prevalence and meta-regression of prevalence time trends will be performed using a random effects model (which allows for differences in estimates due to heterogeneity) with the metaprop31 command in Stata. If possible, these analysis will be repeated for comparison of subgroups reported, primarily for regional subgroups.

    For the objective of establishing which routinely collected health databases are being used and which are available for use in reporting the epidemiology of major lower limb amputation, extracted data will be tabulated where applicable and narratively synthesised.

    Strengths and weaknesses of each database will be evaluated by using the following sources:

    • Relevant sections of each included article.

    • The data sources themselves (from their websites, etc).

    • Published articles that evaluate the strengths and weaknesses of the databases.

    There is potential for the included articles and the data source websites to be positively biased towards their work and so to balance this, published articles that specifically review the potential weaknesses of the data sources will also be used to inform assessment where available.

    Epidemiological calculation definitions

    Embedded Image

    Embedded Image

    Embedded Image

    Embedded Image

    Where Embedded Image refers to the population specified by the study.

    Definitions taken from the Centers for Disease Control and Prevention and the Health Knowledge website managed by the Public Health Action Support Team.32 33

    Patient and public involvement

    Patients and the public were not involved in the design of this study.

    Ethics and dissemination

    As this study does not involve the analysis of confidential patient data, it does not require formal ethics approval.This systematic review aims to build on previous systematic reviews that report the epidemiology of major lower limb amputation by establishing a current estimate of incidence/prevalence/number with time trends and subgroup estimates reported where available. The sources of routinely collected electronic health data used in reporting the epidemiology of major lower limb amputation will be established and discussed. Extensive systematic searches will strengthen the findings of this review. It is anticipated that the results of this review will be able to inform future research on the epidemiology of and regional variation in major lower limb amputation in the UK. After the expected completion data in October 2020, the study will be submitted to a peer-reviewed journal.

    References

    1. ↵
      1. Dillingham TR,
      2. Pezzin LE,
      3. MacKenzie EJ
      . Limb amputation and limb deficiency: epidemiology and recent trends in the United States. South Med J 2002;95:875–83.doi:10.1097/00007611-200208000-00018pmid:http://www.ncbi.nlm.nih.gov/pubmed/12190225
      OpenUrlPubMedWeb of Science
    2. ↵
      1. McDermott MM,
      2. Greenland P,
      3. Liu K, et al
      . Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA 2001;286:1599–606.doi:10.1001/jama.286.13.1599pmid:http://www.ncbi.nlm.nih.gov/pubmed/11585483
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      1. Shu J,
      2. Santulli G
      . Update on peripheral artery disease: epidemiology and evidence-based facts. Atherosclerosis 2018;275:379–81.doi:10.1016/j.atherosclerosis.2018.05.033pmid:http://www.ncbi.nlm.nih.gov/pubmed/29843915
      OpenUrlCrossRefPubMed
    4. ↵
      1. NICE
      . Peripheral arterial disease quality standard (QS52), 2014. Available: https://www.nice.org.uk/guidance/qs52/chapter/Introduction
    5. ↵
      1. Steffen LM,
      2. Duprez DA,
      3. Boucher JL, et al
      . Management of peripheral arterial disease. Diabetes Spectrum 2008;21:171–7.doi:10.2337/diaspect.21.3.171
      OpenUrlAbstract/FREE Full Text
    6. ↵
      1. Cea-Soriano L,
      2. Fowkes FGR,
      3. Johansson S, et al
      . Time trends in peripheral artery disease incidence, prevalence and secondary preventive therapy: a cohort study in the health improvement network in the UK. BMJ Open 2018;8:e018184.doi:10.1136/bmjopen-2017-018184pmid:http://www.ncbi.nlm.nih.gov/pubmed/29358428
      OpenUrlAbstract/FREE Full Text
    7. ↵
      1. Holman N,
      2. Forouhi NG,
      3. Goyder E, et al
      . The association of public health Observatories (APHO) diabetes prevalence model: estimates of total diabetes prevalence for England, 2010-2030. Diabet Med 2011;28:575–82.doi:10.1111/j.1464-5491.2010.03216.xpmid:http://www.ncbi.nlm.nih.gov/pubmed/21480968
      OpenUrlCrossRefPubMed
    8. ↵
      1. Criqui MH,
      2. Aboyans V
      . Epidemiology of peripheral artery disease. Circ Res 2015;116:1509–26.doi:10.1161/CIRCRESAHA.116.303849pmid:http://www.ncbi.nlm.nih.gov/pubmed/25908725
      OpenUrlAbstract/FREE Full Text
    9. ↵
      1. Holman N,
      2. Young RJ,
      3. Jeffcoate WJ
      . Variation in the recorded incidence of amputation of the lower limb in England. Diabetologia 2012;55:1919–25.doi:10.1007/s00125-012-2468-6pmid:http://www.ncbi.nlm.nih.gov/pubmed/22398645
      OpenUrlCrossRefPubMedWeb of Science
    10. ↵
      1. Moxey PW,
      2. Hofman D,
      3. Hinchliffe RJ, et al
      . Epidemiological study of lower limb amputation in England between 2003 and 2008. Br J Surg 2010;97:1348–53.doi:10.1002/bjs.7092pmid:http://www.ncbi.nlm.nih.gov/pubmed/20632310
      OpenUrlCrossRefPubMed
    11. ↵
      1. Heikkila K,
      2. Mitchell DC,
      3. Loftus IM, et al
      . Improving 1-Year Outcomes of Infrainguinal Limb Revascularization: Population-Based Cohort Study of 104 000 Patients in England. Circulation 2018;137:1921–33.doi:10.1161/CIRCULATIONAHA.117.029834pmid:http://www.ncbi.nlm.nih.gov/pubmed/29317447
      OpenUrlAbstract/FREE Full Text
    12. ↵
      1. Shephard E,
      2. Stapley S,
      3. Hamilton W
      . The use of electronic databases in primary care research. Fam Pract 2011;28:352–4.doi:10.1093/fampra/cmr039pmid:http://www.ncbi.nlm.nih.gov/pubmed/21791530
      OpenUrlCrossRefPubMed
    13. ↵
      1. Burns EM,
      2. Rigby E,
      3. Mamidanna R, et al
      . Systematic review of discharge coding accuracy. J Public Health 2012;34:138–48.doi:10.1093/pubmed/fdr054pmid:http://www.ncbi.nlm.nih.gov/pubmed/21795302
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      1. NHS-Digital
      . SNOMED CT implementation in primary care 2019 .. Available: https://digital.nhs.uk/services/terminology-and-classifications/snomed-ct/snomed-ct-implementation-in-primary-care [Accessed 21 Mar 2019].
    15. ↵
      1. Tate AR,
      2. Dungey S,
      3. Glew S, et al
      . Quality of recording of diabetes in the UK: how does the GP's method of coding clinical data affect incidence estimates? cross-sectional study using the CPRD database. BMJ Open 2017;7:e012905.doi:10.1136/bmjopen-2016-012905pmid:http://www.ncbi.nlm.nih.gov/pubmed/28122831
      OpenUrlAbstract/FREE Full Text
    16. ↵
      1. NHS-Digital
      . Hospital episode statistics (HES), 2019. Available: https://digital.nhs.uk/data-and-information/data-tools-and-services/data-services/hospital-episode-statistics [Accessed 26 Mar 2019].
    17. ↵
      1. CPRD
      . Clinical practice research Datalink, 2019. Available: https://www.cprd.com
    18. ↵
      1. Herrett E,
      2. Gallagher AM,
      3. Bhaskaran K, et al
      . Data resource profile: clinical practice research Datalink (CPRD). Int J Epidemiol 2015;44:827–36.doi:10.1093/ije/dyv098pmid:http://www.ncbi.nlm.nih.gov/pubmed/26050254
      OpenUrlCrossRefPubMed
    19. ↵
      1. Ahmad N,
      2. Thomas GN,
      3. Gill P, et al
      . The prevalence of major lower limb amputation in the diabetic and non-diabetic population of England 2003-2013. Diab Vasc Dis Res 2016;13:348–53.doi:10.1177/1479164116651390pmid:http://www.ncbi.nlm.nih.gov/pubmed/27334482
      OpenUrlCrossRefPubMed
    20. ↵
      1. Davies M,
      2. Burdett L,
      3. Bowling F, et al
      . The epidemiology of major lower-limb amputation in England: a systematic review highlighting methodological differences of reported trials. Diabet Foot Ankle 2019;22:53–61.
      OpenUrl
    21. ↵
      1. Moher D,
      2. Liberati A,
      3. Tetzlaff J, et al
      . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.doi:10.1371/journal.pmed.1000097pmid:http://www.ncbi.nlm.nih.gov/pubmed/19621072
      OpenUrlCrossRefPubMed
    22. ↵
      1. Moher D,
      2. Shamseer L,
      3. Clarke M, et al
      . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:1.doi:10.1186/2046-4053-4-1pmid:http://www.ncbi.nlm.nih.gov/pubmed/25554246
      OpenUrlCrossRefPubMed
    23. ↵
      1. Ayiku L,
      2. Levay P,
      3. Hudson T, et al
      . The Medline UK filter: development and validation of a geographic search filter to retrieve research about the UK from OVID Medline. Health Info Libr J 2017;34:200–16.doi:10.1111/hir.12187pmid:http://www.ncbi.nlm.nih.gov/pubmed/28703418
      OpenUrlPubMed
    24. ↵
      1. Ayiku L,
      2. Levay P,
      3. Hudson T, et al
      . The Embase UK filter: validation of a geographic search filter to retrieve research about the UK from OVID Embase. Health Info Libr J 2019;36:121–33.doi:10.1111/hir.12252pmid:http://www.ncbi.nlm.nih.gov/pubmed/30912233
      OpenUrlPubMed
    25. ↵
      1. Conte MS,
      2. Bradbury AW,
      3. Kolh P, et al
      . Global vascular guidelines on the management of chronic limb-threatening ischemia. Eur J Vasc Endovasc Surg 2019;58:S1–109.doi:10.1016/j.ejvs.2019.05.006pmid:http://www.ncbi.nlm.nih.gov/pubmed/31182334
      OpenUrlPubMed
    26. ↵
      1. Lang SH,
      2. Swift SL,
      3. White H, et al
      . A systematic review of the prevalence of DNA damage response gene mutations in prostate cancer. Int J Oncol 2019;55:597–616.doi:10.3892/ijo.2019.4842pmid:http://www.ncbi.nlm.nih.gov/pubmed/31322208
      OpenUrlPubMed
    27. ↵
      1. Schmucker C,
      2. Kapp P,
      3. Motschall E, et al
      . Prevalence of hearing loss and use of hearing AIDS among children and adolescents in Germany: a systematic review. BMC Public Health 2019;19:1277.doi:10.1186/s12889-019-7602-7pmid:http://www.ncbi.nlm.nih.gov/pubmed/31533687
      OpenUrlPubMed
    28. ↵
      1. Vaziri S,
      2. Fakouri F,
      3. Mirzaei M, et al
      . Prevalence of medical errors in Iran: a systematic review and meta-analysis. BMC Health Serv Res 2019;19:622.doi:10.1186/s12913-019-4464-8pmid:http://www.ncbi.nlm.nih.gov/pubmed/31477096
      OpenUrlPubMed
    29. ↵
      1. Munn Z,
      2. Moola S,
      3. Lisy K, et al
      . Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc 2015;13:147–53.doi:10.1097/XEB.0000000000000054pmid:http://www.ncbi.nlm.nih.gov/pubmed/26317388
      OpenUrlPubMed
    30. ↵
      1. Moola SMZ,
      2. Tufanaru C,
      3. Aromataris E, et al
      . Chapter 7: Systematic reviews of etiology and risk. In: Joanna Briggs Institute reviewer's manual, 2017. https://reviewersmanual.joannabriggs.org/
    31. ↵
      1. Nyaga VN,
      2. Arbyn M,
      3. Aerts M
      . Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health 2014;72:39.doi:10.1186/2049-3258-72-39pmid:http://www.ncbi.nlm.nih.gov/pubmed/25810908
      OpenUrlCrossRefPubMed
    32. ↵
      1. Barratt HK,
      2. Shantikumar M,
      3. Numerators S
      . Denominators and populations at risk: health knowledge, 2018. Available: https://www.healthknowledge.org.uk/public-health-textbook/research-methods/1a-epidemiology/numerators-denominators-populations [Accessed 07 Jan 2020].
    33. ↵
      1. CDC
      . Principles of Epidemiology in Public Health Practice - Lesson 3: Measures of Risk. Section 2: Morbidity Frequency Measures: Centres for Disease Control and Prevention, 2012. Available: https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section2.html [Accessed 7 Jan 2020].

    Footnotes

    • Author contributions AM, LJG and RDS were all involved in and accountable for each stage of the writing of the systematic review protocol and thus all contributed to the concept and design, the drafting and revising and approving the final version. The search strategy for grey and peer reviewed literature were created by CJP and AM.

    • Funding AM and RDS are funded by a charitable donation from the George Davies Charitable Trust (registered charity number: 1024818).

    • Disclaimer The funder had no role in the development of the systematic review protocol.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.