Detection of Familial Hypercholesterolaemia in Cardiovascular Disease Registry

NCT ID: NCT02778646

Last Updated: 2016-05-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1622948 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2014-12-31

Brief Summary

Familial hypercholesterolaemia (FH) is an autosomal dominant somatic mutation commonly located on the LDL-receptor, APOB, and PCKS9 gene. The estimated prevalence of homozygous FH is estimated at 1 in a million, whereas the prevalence of heterozygous FH ranges from 1/500-1/200 (0.2-0.5%) of the general population. The majority of individuals suffering from FH remain undiagnosed and without treatment. Using preexisting clinical guidelines, this study scored patients within national cardiovascular disease (CVD) registries for FH with the aim of evaluating prevalence of FH among individuals suffering from premature cardiac events within the UK.

Following scoring of the registry, this study also examined the relationship between cholesterol and survival after a premature event in order to understand the possible ramifications of untreated FH on patient survival.

Detailed Description

Familial Hypercholesterolaemia (FH) is a genetic disorder caused by a mutation in the low-density lipoprotein receptor (LDL-R) gene. Individuals suffering from FH experience elevated cholesterol levels that are outside of the accepted range of healthy cholesterol levels. When left untreated FH may cause complications in cardiovascular health and may cause premature cardiac events. Current screening methods for this disease do not successfully diagnose the majority of FH cases.

This study applies three clinical diagnostic tools--Dutch Lipid Clinic Network Criteria (DLCN-Criteria), Make Early Diagnosis to Prevent Early Deaths (MEDPED) criteria, and the Simon Broome Register Criteria--within national registries in order to define possible, probable, and definite cases of FH. The national registries used for this study are the Myocardial Ischaemia National Audit Project (MINAP) and National Audit of Percutaneous Coronary Intervention (BCIS) audit.

Following scoring of patients, a one-year and 30-day survival model were created in order to assess the effect of elevated cholesterol on survival, as suspected FH patients will have elevated cholesterol levels.

Data within MINAP ranges from 2003-2013 and data from BCIS ranges from 2007-2014.

Patient information within the audits was collected following admission to English and Welsh hospitals following a coronary event or percutaneous coronary intervention (PCI). Information related to survival and mortality was collected annually within each audit.

Participants for this study were those experiencing a premature cardiovascular event or coronary intervention (men <55 and women<60).

Conditions

Familial Hypercholesterolemia; Cardiac Event; Percutaneous Coronary Intervention

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

MINAP Audit

Individuals within this group are those that have been admitted into a United Kingdom (UK) based hospital following a major cardiac event. The FH status of individuals within this group is unknown.

No interventions assigned to this group

BCIS Audit

Individuals within this group are those who have undergone percutaneous coronary intervention in the United Kingdom (UK). The FH status of individuals within this group is unknown.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Experienced a cardiac event and is therefore entered in CVD audit
• First registered event within audits

Exclusion Criteria

• Under age 18
• Previous diagnosis of FH

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aegerion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joy Ayemoba, MSc

Role: STUDY_CHAIR

UCL

John Deanfield, MD

Role: PRINCIPAL_INVESTIGATOR

UCL

Owen Nicholas, PhD

Role: STUDY_DIRECTOR

UCL

Riyaz Patel, MD

Role: STUDY_CHAIR

UCL

References

Bell DA, Kirke AB, Barbour R, Southwell L, Pang J, Burrows S, Watts GF. Can patients be accurately assessed for familial hypercholesterolaemia in primary care? Heart Lung Circ. 2014 Dec;23(12):1153-7. doi: 10.1016/j.hlc.2014.06.015. Epub 2014 Jul 5.

Reference Type: BACKGROUND

PMID: 25065543 (View on PubMed)

Chen CX, Hay JW. Cost-effectiveness analysis of alternative screening and treatment strategies for heterozygous familial hypercholesterolemia in the United States. Int J Cardiol. 2015 Feb 15;181:417-24. doi: 10.1016/j.ijcard.2014.12.070. Epub 2014 Dec 24.

Reference Type: BACKGROUND

PMID: 25569270 (View on PubMed)

Futema M, Kumari M, Boustred C, Kivimaki M, Humphries SE. Would raising the total cholesterol diagnostic cut-off from 7.5 mmol/L to 9.3 mmol/L improve detection rate of patients with monogenic familial hypercholesterolaemia? Atherosclerosis. 2015 Apr;239(2):295-8. doi: 10.1016/j.atherosclerosis.2015.01.028. Epub 2015 Jan 28.

Reference Type: BACKGROUND

PMID: 25682026 (View on PubMed)

Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, Daniels SR, Gidding SS, de Ferranti SD, Ito MK, McGowan MP, Moriarty PM, Cromwell WC, Ross JL, Ziajka PE. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 May-Jun;5(3):133-140. doi: 10.1016/j.jacl.2011.03.001. Epub 2011 Mar 11.

Reference Type: BACKGROUND

PMID: 21600517 (View on PubMed)

Gray J, Jaiyeola A, Whiting M, Modell M, Wierzbicki AS. Identifying patients with familial hypercholesterolaemia in primary care: an informatics-based approach in one primary care centre. Heart. 2008 Jun;94(6):754-8. doi: 10.1136/hrt.2006.107391. Epub 2007 Jun 17.

Reference Type: BACKGROUND

PMID: 17575326 (View on PubMed)

Haralambos K, Whatley SD, Edwards R, Gingell R, Townsend D, Ashfield-Watt P, Lansberg P, Datta DB, McDowell IF. Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales. Atherosclerosis. 2015 May;240(1):190-6. doi: 10.1016/j.atherosclerosis.2015.03.003. Epub 2015 Mar 6.

Reference Type: BACKGROUND

PMID: 25797312 (View on PubMed)

Kirke AB, Barbour RA, Burrows S, Bell DA, Vickery AW, Emery J, Watts GF. Systematic detection of familial hypercholesterolaemia in primary health care: a community based prospective study of three methods. Heart Lung Circ. 2015 Mar;24(3):250-6. doi: 10.1016/j.hlc.2014.09.011. Epub 2014 Sep 30.

Reference Type: BACKGROUND

PMID: 25445428 (View on PubMed)

Kirke A, Watts GF, Emery J. Detecting familial hypercholesterolaemia in general practice. Aust Fam Physician. 2012 Dec;41(12):965-8.

Reference Type: BACKGROUND

PMID: 23210121 (View on PubMed)

Nair DR, Sharifi M, Al-Rasadi K. Familial hypercholesterolaemia. Curr Opin Cardiol. 2014 Jul;29(4):381-8. doi: 10.1097/HCO.0000000000000083.

Reference Type: BACKGROUND

PMID: 24870549 (View on PubMed)

Nice.org.uk,. 'Identification And Management Of Familial Hypercholesterolaemia | Guidance And Guidelines | NICE'. N.p., 2008. Web. 27 Apr. 2015.

Reference Type: BACKGROUND

Watts GF, Shaw JE, Pang J, Magliano DJ, Jennings GL, Carrington MJ. Prevalence and treatment of familial hypercholesterolaemia in Australian communities. Int J Cardiol. 2015 Apr 15;185:69-71. doi: 10.1016/j.ijcard.2015.03.027. Epub 2015 Mar 3. No abstract available.

Reference Type: BACKGROUND

PMID: 25791093 (View on PubMed)

Weng SF, Kai J, Andrew Neil H, Humphries SE, Qureshi N. Improving identification of familial hypercholesterolaemia in primary care: derivation and validation of the familial hypercholesterolaemia case ascertainment tool (FAMCAT). Atherosclerosis. 2015 Feb;238(2):336-43. doi: 10.1016/j.atherosclerosis.2014.12.034. Epub 2014 Dec 20.

Reference Type: BACKGROUND

PMID: 25555265 (View on PubMed)

Arnold SV, Kosiborod M, Tang F, Zhao Z, McCollam PL, Birt J, Spertus JA. Changes in low-density lipoprotein cholesterol levels after discharge for acute myocardial infarction in a real-world patient population. Am J Epidemiol. 2014 Jun 1;179(11):1293-300. doi: 10.1093/aje/kwu060. Epub 2014 Apr 16.

Reference Type: BACKGROUND

PMID: 24743066 (View on PubMed)

Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol. 2004 Sep 1;160(5):407-20. doi: 10.1093/aje/kwh236.

Reference Type: BACKGROUND

PMID: 15321837 (View on PubMed)

Barth JH, Jackson BM, Farrin AJ, Efthymiou M, Worthy G, Copeland J, Bailey KM, Romaine SP, Balmforth AJ, McCormack T, Whitehead A, Flather MD, Nixon J, Hall AS; SPACE ROCKET Trial Group. Change in serum lipids after acute coronary syndromes: secondary analysis of SPACE ROCKET study data and a comparative literature review. Clin Chem. 2010 Oct;56(10):1592-8. doi: 10.1373/clinchem.2010.145631. Epub 2010 Aug 20.

Reference Type: BACKGROUND

PMID: 20729301 (View on PubMed)

Besseling J, Kindt I, Hof M, Kastelein JJ, Hutten BA, Hovingh GK. Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14,000 mutation carriers. Atherosclerosis. 2014 Mar;233(1):219-23. doi: 10.1016/j.atherosclerosis.2013.12.020. Epub 2014 Jan 11.

Reference Type: BACKGROUND

PMID: 24529147 (View on PubMed)

Chakko S, Myerburg RJ. Cardiac complications of cocaine abuse. Clin Cardiol. 1995 Feb;18(2):67-72. doi: 10.1002/clc.4960180206.

Reference Type: BACKGROUND

PMID: 7720292 (View on PubMed)

Charniak, Eugene. 'Bayesian Networks Without Tears'. AI Magazine 12.4 (1991): 50-63. Print.

Reference Type: BACKGROUND

De Castro-Orós, Isabel, Miguel Pocoví, and Fernando Civeira. 'The Fine Line Between Familial And Polygenic Hypercholesterolemia'. Clinical Lipidology 8.3 (2013): 303-306. Web.

Reference Type: BACKGROUND

de Ferranti SD, de Boer IH, Fonseca V, Fox CS, Golden SH, Lavie CJ, Magge SN, Marx N, McGuire DK, Orchard TJ, Zinman B, Eckel RH. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014 Sep 23;130(13):1110-30. doi: 10.1161/CIR.0000000000000034. Epub 2014 Aug 11. No abstract available.

Reference Type: BACKGROUND

PMID: 25114208 (View on PubMed)

Gaziano JM, Hennekens CH, Satterfield S, Roy C, Sesso HD, Breslow JL, Buring JE. Clinical utility of lipid and lipoprotein levels during hospitalization for acute myocardial infarction. Vasc Med. 1999;4(4):227-31. doi: 10.1177/1358836X9900400404.

Reference Type: BACKGROUND

PMID: 10613626 (View on PubMed)

Kasim S, O'Donabhain R, Mcfadden E. Cocaine-associated myocardial infarction: should they all be stented? Case Rep Cardiol. 2011;2011:347806. doi: 10.1155/2011/347806. Epub 2011 Jul 19.

Reference Type: BACKGROUND

PMID: 24826216 (View on PubMed)

Mabuchi H, Higashikata T, Nohara A, Lu H, Yu WX, Nozue T, Noji Y, Katsuda S, Kawashiri MA, Inazu A, Kobayashi J, Koizumi J. Cutoff point separating affected and unaffected familial hypercholesterolemic patients validated by LDL-receptor gene mutants. J Atheroscler Thromb. 2005;12(1):35-40. doi: 10.5551/jat.12.35.

Reference Type: BACKGROUND

PMID: 15725694 (View on PubMed)

Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE. Triggering of myocardial infarction by cocaine. Circulation. 1999 Jun 1;99(21):2737-41. doi: 10.1161/01.cir.99.21.2737.

Reference Type: BACKGROUND

PMID: 10351966 (View on PubMed)

Mundal L, Sarancic M, Ose L, Iversen PO, Borgan JK, Veierod MB, Leren TP, Retterstol K. Mortality among patients with familial hypercholesterolemia: a registry-based study in Norway, 1992-2010. J Am Heart Assoc. 2014 Dec 2;3(6):e001236. doi: 10.1161/JAHA.114.001236.

Reference Type: BACKGROUND

PMID: 25468658 (View on PubMed)

Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-90a. doi: 10.1093/eurheartj/eht273. Epub 2013 Aug 15.

Reference Type: BACKGROUND

PMID: 23956253 (View on PubMed)

Orchard TJ, Costacou T, Kretowski A, Nesto RW. Type 1 diabetes and coronary artery disease. Diabetes Care. 2006 Nov;29(11):2528-38. doi: 10.2337/dc06-1161. No abstract available.

Reference Type: BACKGROUND

PMID: 17065698 (View on PubMed)

Qureshi AI, Chaudhry SA, Suri MF. Cocaine use and the likelihood of cardiovascular and all-cause mortality: data from the Third National Health and Nutrition Examination Survey Mortality Follow-up Study. J Vasc Interv Neurol. 2014 May;7(1):76-82.

Reference Type: BACKGROUND

PMID: 24920992 (View on PubMed)

Raal FJ, Pilcher GJ, Panz VR, van Deventer HE, Brice BC, Blom DJ, Marais AD. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation. 2011 Nov 15;124(20):2202-7. doi: 10.1161/CIRCULATIONAHA.111.042523. Epub 2011 Oct 10.

Reference Type: BACKGROUND

PMID: 21986285 (View on PubMed)

Schnell O, Cappuccio F, Genovese S, Standl E, Valensi P, Ceriello A. Type 1 diabetes and cardiovascular disease. Cardiovasc Diabetol. 2013 Oct 28;12:156. doi: 10.1186/1475-2840-12-156.

Reference Type: BACKGROUND

PMID: 24165454 (View on PubMed)

Sijbrands EJ, Westendorp RG, Defesche JC, de Meier PH, Smelt AH, Kastelein JJ. Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study. BMJ. 2001 Apr 28;322(7293):1019-23. doi: 10.1136/bmj.322.7293.1019.

Reference Type: BACKGROUND

PMID: 11325764 (View on PubMed)

Spiegelhalter, D. J, K. R Abrams, and Jonathan P Myles. Bayesian Approaches To Clinical Trials And Health-Care Evaluation. Chichester: John Wiley & Sons, 2004. Print.

Reference Type: BACKGROUND

Stein EA, Raal FJ. Polygenic familial hypercholesterolaemia: does it matter? Lancet. 2013 Apr 13;381(9874):1255-7. doi: 10.1016/S0140-6736(13)60187-7. Epub 2013 Feb 22. No abstract available.

Reference Type: BACKGROUND

PMID: 23433574 (View on PubMed)

Sterne JA, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, Wood AM, Carpenter JR. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009 Jun 29;338:b2393. doi: 10.1136/bmj.b2393.

Reference Type: BACKGROUND

PMID: 19564179 (View on PubMed)

Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DC, Liem AH, Heeringa J, Witteman JC, Lansberg PJ, Kastelein JJ, Sijbrands EJ. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008 Nov 11;337:a2423. doi: 10.1136/bmj.a2423.

Reference Type: BACKGROUND

PMID: 19001495 (View on PubMed)

Wald DS, Bangash FA, Bestwick JP. Prevalence of DNA-confirmed familial hypercholesterolaemia in young patients with myocardial infarction. Eur J Intern Med. 2015 Mar;26(2):127-30. doi: 10.1016/j.ejim.2015.01.014. Epub 2015 Feb 11.

Reference Type: BACKGROUND

PMID: 25682442 (View on PubMed)

Wattanasuwan N, Khan IA, Gowda RM, Vasavada BC, Sacchi TJ. Effect of acute myocardial infarction on cholesterol ratios. Chest. 2001 Oct;120(4):1196-9. doi: 10.1378/chest.120.4.1196.

Reference Type: BACKGROUND

PMID: 11591560 (View on PubMed)

World Health Organization,. Familial Hypercholesterolaemia. Geneva, Switzerland: Human Genetics Programme, 1998. Print. Annex Progress Report.

Reference Type: BACKGROUND

Sun LY, Zhang YB, Jiang L, Wan N, Wu WF, Pan XD, Yu J, Zhang F, Wang LY. Erratum: Identification of the gene defect responsible for severe hypercholesterolaemia using whole-exome sequencing. Sci Rep. 2015 Aug 3;5:12656. doi: 10.1038/srep12656. No abstract available.

Reference Type: BACKGROUND

PMID: 26237740 (View on PubMed)

Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Scientific Steering Committee on behalf of the Simon Broome Register Group. Atherosclerosis. 1999 Jan;142(1):105-12.

Reference Type: BACKGROUND

PMID: 9920511 (View on PubMed)

Moons KG, Donders RA, Stijnen T, Harrell FE Jr. Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol. 2006 Oct;59(10):1092-101. doi: 10.1016/j.jclinepi.2006.01.009. Epub 2006 Jun 19.

Reference Type: BACKGROUND

PMID: 16980150 (View on PubMed)

Medeiros AM, Alves AC, Bourbon M. Mutational analysis of a cohort with clinical diagnosis of familial hypercholesterolemia: considerations for genetic diagnosis improvement. Genet Med. 2016 Apr;18(4):316-24. doi: 10.1038/gim.2015.71. Epub 2015 May 28.

Reference Type: BACKGROUND

PMID: 26020417 (View on PubMed)

McAllister KS, Ludman PF, Hulme W, de Belder MA, Stables R, Chowdhary S, Mamas MA, Sperrin M, Buchan IE; British Cardiovascular Intervention Society and the National Institute for Cardiovascular Outcomes Research. A contemporary risk model for predicting 30-day mortality following percutaneous coronary intervention in England and Wales. Int J Cardiol. 2016 May 1;210:125-32. doi: 10.1016/j.ijcard.2016.02.085. Epub 2016 Feb 17.

Reference Type: BACKGROUND

PMID: 26942330 (View on PubMed)

Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003 May;168(1):1-14. doi: 10.1016/s0021-9150(02)00330-1.

Reference Type: BACKGROUND

PMID: 12732381 (View on PubMed)

Do R, Stitziel NO, Won HH, Jorgensen AB, Duga S, Angelica Merlini P, Kiezun A, Farrall M, Goel A, Zuk O, Guella I, Asselta R, Lange LA, Peloso GM, Auer PL; NHLBI Exome Sequencing Project; Girelli D, Martinelli N, Farlow DN, DePristo MA, Roberts R, Stewart AF, Saleheen D, Danesh J, Epstein SE, Sivapalaratnam S, Hovingh GK, Kastelein JJ, Samani NJ, Schunkert H, Erdmann J, Shah SH, Kraus WE, Davies R, Nikpay M, Johansen CT, Wang J, Hegele RA, Hechter E, Marz W, Kleber ME, Huang J, Johnson AD, Li M, Burke GL, Gross M, Liu Y, Assimes TL, Heiss G, Lange EM, Folsom AR, Taylor HA, Olivieri O, Hamsten A, Clarke R, Reilly DF, Yin W, Rivas MA, Donnelly P, Rossouw JE, Psaty BM, Herrington DM, Wilson JG, Rich SS, Bamshad MJ, Tracy RP, Cupples LA, Rader DJ, Reilly MP, Spertus JA, Cresci S, Hartiala J, Tang WH, Hazen SL, Allayee H, Reiner AP, Carlson CS, Kooperberg C, Jackson RD, Boerwinkle E, Lander ES, Schwartz SM, Siscovick DS, McPherson R, Tybjaerg-Hansen A, Abecasis GR, Watkins H, Nickerson DA, Ardissino D, Sunyaev SR, O'Donnell CJ, Altshuler D, Gabriel S, Kathiresan S. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015 Feb 5;518(7537):102-6. doi: 10.1038/nature13917. Epub 2014 Dec 10.

Reference Type: BACKGROUND

PMID: 25487149 (View on PubMed)

Damgaard D, Larsen ML, Nissen PH, Jensen JM, Jensen HK, Soerensen VR, Jensen LG, Faergeman O. The relationship of molecular genetic to clinical diagnosis of familial hypercholesterolemia in a Danish population. Atherosclerosis. 2005 May;180(1):155-60. doi: 10.1016/j.atherosclerosis.2004.12.001. Epub 2005 Jan 12.

Reference Type: BACKGROUND

PMID: 15823288 (View on PubMed)

Civeira F, Ros E, Jarauta E, Plana N, Zambon D, Puzo J, Martinez de Esteban JP, Ferrando J, Zabala S, Almagro F, Gimeno JA, Masana L, Pocovi M. Comparison of genetic versus clinical diagnosis in familial hypercholesterolemia. Am J Cardiol. 2008 Nov 1;102(9):1187-93, 1193.e1. doi: 10.1016/j.amjcard.2008.06.056. Epub 2008 Aug 27.

Reference Type: BACKGROUND

PMID: 18940289 (View on PubMed)

Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012 Nov;97(11):3956-64. doi: 10.1210/jc.2012-1563. Epub 2012 Aug 14.

Reference Type: BACKGROUND

PMID: 22893714 (View on PubMed)

Al-Rasadi K, Al-Waili K, Al-Sabti HA, Al-Hinai A, Al-Hashmi K, Al-Zakwani I, Banerjee Y. Criteria for Diagnosis of Familial Hypercholesterolemia: A Comprehensive Analysis of the Different Guidelines, Appraising their Suitability in the Omani Arab Population. Oman Med J. 2014 Mar;29(2):85-91. doi: 10.5001/omj.2014.22.

Reference Type: BACKGROUND

PMID: 24715932 (View on PubMed)

Cattle BA, Baxter PD, Greenwood DC, Gale CP, West RM. Multiple imputation for completion of a national clinical audit dataset. Stat Med. 2011 Sep 30;30(22):2736-53. doi: 10.1002/sim.4314. Epub 2011 Jul 22.

Reference Type: BACKGROUND

PMID: 21786284 (View on PubMed)

Other Identifiers

NCR-15-07

Identifier Type: -

Identifier Source: org_study_id