Skip to main content
Top
Published in: BMC Medical Informatics and Decision Making 1/2021

Open Access 01-12-2021 | Stroke | Research article

An informatics consult approach for generating clinical evidence for treatment decisions

Authors: Alvina G. Lai, Wai Hoong Chang, Constantinos A. Parisinos, Michail Katsoulis, Ruth M. Blackburn, Anoop D. Shah, Vincent Nguyen, Spiros Denaxas, George Davey Smith, Tom R. Gaunt, Krishnarajah Nirantharakumar, Murray P. Cox, Donall Forde, Folkert W. Asselbergs, Steve Harris, Sylvia Richardson, Reecha Sofat, Richard J. B. Dobson, Aroon Hingorani, Riyaz Patel, Jonathan Sterne, Amitava Banerjee, Alastair K. Denniston, Simon Ball, Neil J. Sebire, Nigam H. Shah, Graham R. Foster, Bryan Williams, Harry Hemingway

Published in: BMC Medical Informatics and Decision Making | Issue 1/2021

Login to get access

Abstract

Background

An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.

Methods

We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.

Results

We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39–1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49–0.76) and ischaemic stroke (HR = 0.27, CI 0.08–0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.

Conclusion

We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on ‘patients like me’. We identify the key challenges in offering such an Informatics Consult as a service.
Appendix
Available only for authorised users
Literature
1.
go back to reference van Dijk WB, Grobbee DE, de Vries MC, Groenwold RHH, van der Graaf R, Schuit E. A systematic breakdown of the levels of evidence supporting the European Society of Cardiology guidelines. Eur J Prev Cardiol. 2019;26:1944–52.CrossRef van Dijk WB, Grobbee DE, de Vries MC, Groenwold RHH, van der Graaf R, Schuit E. A systematic breakdown of the levels of evidence supporting the European Society of Cardiology guidelines. Eur J Prev Cardiol. 2019;26:1944–52.CrossRef
2.
go back to reference Meyer C, Bowers A, Wayant C, Checketts J, Scott J, Musuvathy S, et al. Scientific evidence underlying the American College of Gastroenterology’s clinical practice guidelines. PLoS ONE. 2018;13:e0204720.CrossRef Meyer C, Bowers A, Wayant C, Checketts J, Scott J, Musuvathy S, et al. Scientific evidence underlying the American College of Gastroenterology’s clinical practice guidelines. PLoS ONE. 2018;13:e0204720.CrossRef
3.
go back to reference Koh C, Zhao X, Samala N, Sakiani S, Liang TJ, Talwalkar JA. AASLD clinical practice guidelines: a critical review of scientific evidence and evolving recommendations. Hepatology. 2013;58:2142–52.CrossRef Koh C, Zhao X, Samala N, Sakiani S, Liang TJ, Talwalkar JA. AASLD clinical practice guidelines: a critical review of scientific evidence and evolving recommendations. Hepatology. 2013;58:2142–52.CrossRef
4.
go back to reference Fanaroff AC, Califf RM, Windecker S, Smith SC, Lopes RD. Levels of evidence supporting American College of Cardiology/American Heart Association and European Society of Cardiology Guidelines, 2008–2018. JAMA. 2019;321:1069–80.CrossRef Fanaroff AC, Califf RM, Windecker S, Smith SC, Lopes RD. Levels of evidence supporting American College of Cardiology/American Heart Association and European Society of Cardiology Guidelines, 2008–2018. JAMA. 2019;321:1069–80.CrossRef
5.
go back to reference Tricoci P, Allen JM, Kramer JM, Califf RM, Smith SC. Scientific evidence underlying the ACC/AHA clinical practice guidelines. JAMA. 2009;301:831–41.CrossRef Tricoci P, Allen JM, Kramer JM, Califf RM, Smith SC. Scientific evidence underlying the ACC/AHA clinical practice guidelines. JAMA. 2009;301:831–41.CrossRef
6.
go back to reference Du Vaure CB, Dechartres A, Battin C, Ravaud P, Boutron I. Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials. gov: a systematic review of registration details. BMJ Open. 2016;6:e012265.CrossRef Du Vaure CB, Dechartres A, Battin C, Ravaud P, Boutron I. Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials. gov: a systematic review of registration details. BMJ Open. 2016;6:e012265.CrossRef
9.
go back to reference Longhurst CA, Harrington RA, Shah NH. A “green button” for using aggregate patient data at the point of care. Health Aff. 2014;33:1229–35.CrossRef Longhurst CA, Harrington RA, Shah NH. A “green button” for using aggregate patient data at the point of care. Health Aff. 2014;33:1229–35.CrossRef
10.
go back to reference Callahan A, Gombar S, Jung K, Steinberg E, Harrington R, Shah NH. Delivering on-demand evidence via an informatics consultation service, pp. 3–5. Callahan A, Gombar S, Jung K, Steinberg E, Harrington R, Shah NH. Delivering on-demand evidence via an informatics consultation service, pp. 3–5.
11.
go back to reference Schuler A, Callahan A, Jung K, Shah NH. Performing an informatics consult: methods and challenges. J Am Coll Radiol. 2018;15:563–8.CrossRef Schuler A, Callahan A, Jung K, Shah NH. Performing an informatics consult: methods and challenges. J Am Coll Radiol. 2018;15:563–8.CrossRef
12.
go back to reference Davies NM, Holmes M V., Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018;362. Davies NM, Holmes M V., Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018;362.
13.
go back to reference Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, et al. Guidelines for performing Mendelian randomization investigations. Wellcome Open Res. 2020;4:186.CrossRef Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, et al. Guidelines for performing Mendelian randomization investigations. Wellcome Open Res. 2020;4:186.CrossRef
14.
go back to reference Hernán MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol. 2016;183:758–64.CrossRef Hernán MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol. 2016;183:758–64.CrossRef
16.
go back to reference Kuan V, Denaxas S, Gonzalez-Izquierdo A, Direk K, Bhatti O, Husain S, et al. A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service. Lancet Digit Heal. 2019;1:e63-77.CrossRef Kuan V, Denaxas S, Gonzalez-Izquierdo A, Direk K, Bhatti O, Husain S, et al. A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service. Lancet Digit Heal. 2019;1:e63-77.CrossRef
17.
go back to reference Denaxas S, Gonzalez-Izquierdo A, Direk K, Fitzpatrick NK, Fatemifar G, Banerjee A, et al. UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER. J Am Med Informatics Assoc. 2019. Denaxas S, Gonzalez-Izquierdo A, Direk K, Fitzpatrick NK, Fatemifar G, Banerjee A, et al. UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER. J Am Med Informatics Assoc. 2019.
18.
go back to reference Dashti HS, Shea MK, Smith CE, Tanaka T, Hruby A, Richardson K, et al. Meta-analysis of genome-wide association studies for circulating phylloquinone concentrations. Am J Clin Nutr. 2014;100:1462–9.CrossRef Dashti HS, Shea MK, Smith CE, Tanaka T, Hruby A, Richardson K, et al. Meta-analysis of genome-wide association studies for circulating phylloquinone concentrations. Am J Clin Nutr. 2014;100:1462–9.CrossRef
19.
go back to reference Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018;50:524–37.CrossRef Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018;50:524–37.CrossRef
20.
go back to reference Yavorska OO, Burgess S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol. 2017;46:1734–9.CrossRef Yavorska OO, Burgess S. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol. 2017;46:1734–9.CrossRef
21.
go back to reference Serper M, Weinberg EM, Cohen JB, Reese PP, Taddei TH, Kaplan DE. Mortality and hepatic decompensation in patients with cirrhosis and atrial fibrillation treated with anticoagulation. Hepatology. 2020;0–3. Serper M, Weinberg EM, Cohen JB, Reese PP, Taddei TH, Kaplan DE. Mortality and hepatic decompensation in patients with cirrhosis and atrial fibrillation treated with anticoagulation. Hepatology. 2020;0–3.
22.
go back to reference Choi J, Kim J, Shim JH, Kim M, Nam GB. Risks versus benefits of anticoagulation for atrial fibrillation in cirrhotic patients. J Cardiovasc Pharmacol. 2017;70:255–62.CrossRef Choi J, Kim J, Shim JH, Kim M, Nam GB. Risks versus benefits of anticoagulation for atrial fibrillation in cirrhotic patients. J Cardiovasc Pharmacol. 2017;70:255–62.CrossRef
23.
go back to reference Kuo L, Chao TF, Liu CJ, Lin YJ, Chang SL, Lo LW, et al. Liver cirrhosis in patients with atrial fibrillation: would oral anticoagulation have a net clinical benefit for stroke prevention? J Am Heart Assoc. 2017;6. Kuo L, Chao TF, Liu CJ, Lin YJ, Chang SL, Lo LW, et al. Liver cirrhosis in patients with atrial fibrillation: would oral anticoagulation have a net clinical benefit for stroke prevention? J Am Heart Assoc. 2017;6.
24.
go back to reference Lee SJ, Uhm JS, Kim JY, Pak HN, Lee MH, Joung B. The safety and efficacy of vitamin K antagonist in patients with atrial fibrillation and liver cirrhosis. Int J Cardiol. 2015;180:185–91.CrossRef Lee SJ, Uhm JS, Kim JY, Pak HN, Lee MH, Joung B. The safety and efficacy of vitamin K antagonist in patients with atrial fibrillation and liver cirrhosis. Int J Cardiol. 2015;180:185–91.CrossRef
25.
go back to reference Ahmad FS, Ricket IM, Hammill BG, Eskenazi L, Robertson HR, Curtis LH, et al. Computable phenotype implementation for a national, multicenter pragmatic clinical trial: lessons learned from ADAPTABLE. Circ Cardiovasc Qual Outcomes. 2020;CIRCOUTCOMES–119. Ahmad FS, Ricket IM, Hammill BG, Eskenazi L, Robertson HR, Curtis LH, et al. Computable phenotype implementation for a national, multicenter pragmatic clinical trial: lessons learned from ADAPTABLE. Circ Cardiovasc Qual Outcomes. 2020;CIRCOUTCOMES–119.
26.
go back to reference Willoughby C, Fridsma D, Chatterjee L, Speakman J, Evans J, Kush R. A standard computable clinical trial protocol: the role of the BRIDG model. Drug Inf J DIJ/Drug Inf Assoc. 2007;41:383–92.CrossRef Willoughby C, Fridsma D, Chatterjee L, Speakman J, Evans J, Kush R. A standard computable clinical trial protocol: the role of the BRIDG model. Drug Inf J DIJ/Drug Inf Assoc. 2007;41:383–92.CrossRef
27.
go back to reference Marshall IJ, Wallace BC. Toward systematic review automation: a practical guide to using machine learning tools in research synthesis. Syst Rev. 2019;8:163.CrossRef Marshall IJ, Wallace BC. Toward systematic review automation: a practical guide to using machine learning tools in research synthesis. Syst Rev. 2019;8:163.CrossRef
28.
go back to reference Kiritchenko S, De Bruijn B, Carini S, Martin J, Sim I. ExaCT: automatic extraction of clinical trial characteristics from journal publications. BMC Med Inform Decis Mak. 2010;10:56.CrossRef Kiritchenko S, De Bruijn B, Carini S, Martin J, Sim I. ExaCT: automatic extraction of clinical trial characteristics from journal publications. BMC Med Inform Decis Mak. 2010;10:56.CrossRef
29.
go back to reference Constantin A, Pettifer S, Voronkov A. PDFX: fully-automated PDF-to-XML conversion of scientific literature. In: Proceedings of the 2013 ACM symposium on Document engineering. 2013. pp. 177–80. Constantin A, Pettifer S, Voronkov A. PDFX: fully-automated PDF-to-XML conversion of scientific literature. In: Proceedings of the 2013 ACM symposium on Document engineering. 2013. pp. 177–80.
30.
go back to reference Parizi RM, Guo L, Bian Y, Azmoodeh A, Dehghantanha A, Choo K-KR. CyberPDF: smart and secure coordinate-based automated health PDF data batch extraction. In: 2018 IEEE/ACM international conference on connected health: applications, systems and engineering technologies (CHASE). 2018. pp. 106–11. Parizi RM, Guo L, Bian Y, Azmoodeh A, Dehghantanha A, Choo K-KR. CyberPDF: smart and secure coordinate-based automated health PDF data batch extraction. In: 2018 IEEE/ACM international conference on connected health: applications, systems and engineering technologies (CHASE). 2018. pp. 106–11.
31.
go back to reference Jacobs AK, Quinn TA, Nelson SJ. Mapping SNOMED-CT concepts to MeSH concepts. In: AMIA annual symposium proceedings. 2006. p. 965. Jacobs AK, Quinn TA, Nelson SJ. Mapping SNOMED-CT concepts to MeSH concepts. In: AMIA annual symposium proceedings. 2006. p. 965.
32.
go back to reference Gokhale KM, Chandan JS, Toulis K, Gkoutos G, Tino P, Nirantharakumar K. Data extraction for epidemiological research (DExtER): a novel tool for automated clinical epidemiology studies. Eur J Epidemiol. 2020;36:1–14. Gokhale KM, Chandan JS, Toulis K, Gkoutos G, Tino P, Nirantharakumar K. Data extraction for epidemiological research (DExtER): a novel tool for automated clinical epidemiology studies. Eur J Epidemiol. 2020;36:1–14.
33.
go back to reference Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.CrossRef Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.CrossRef
34.
go back to reference Vimalananda VG, Gupte G, Seraj SM, Orlander J, Berlowitz D, Fincke BG, et al. Electronic consultations (e-consults) to improve access to specialty care: a systematic review and narrative synthesis. J Telemed Telecare. 2015;21:323–30.CrossRef Vimalananda VG, Gupte G, Seraj SM, Orlander J, Berlowitz D, Fincke BG, et al. Electronic consultations (e-consults) to improve access to specialty care: a systematic review and narrative synthesis. J Telemed Telecare. 2015;21:323–30.CrossRef
36.
go back to reference Larsson SC, Traylor M, Markus HS. Circulating vitamin K1 levels in relation to ischemic stroke and its subtypes: a Mendelian randomization study. Nutrients. 2018;10:1–7. Larsson SC, Traylor M, Markus HS. Circulating vitamin K1 levels in relation to ischemic stroke and its subtypes: a Mendelian randomization study. Nutrients. 2018;10:1–7.
37.
go back to reference Li Y-C, Haug PJ, Lincoln MJ, Turner CW, Pryor TA, Warner HH. Assessing the behavioral impact of a diagnostic decision support system. In: Proceedings of the annual symposium on computer application in medical care. 1995. p. 805. Li Y-C, Haug PJ, Lincoln MJ, Turner CW, Pryor TA, Warner HH. Assessing the behavioral impact of a diagnostic decision support system. In: Proceedings of the annual symposium on computer application in medical care. 1995. p. 805.
38.
go back to reference Plante DA, Kassirer JP, Zarin DA, Pauker SG. Clinical decision consultation service. Am J Med. 1986;80:1169–76.CrossRef Plante DA, Kassirer JP, Zarin DA, Pauker SG. Clinical decision consultation service. Am J Med. 1986;80:1169–76.CrossRef
39.
go back to reference Mouhayar E, Salahudeen A. Hypertension in cancer patients. Texas Hear Inst J. 2011;38:263. Mouhayar E, Salahudeen A. Hypertension in cancer patients. Texas Hear Inst J. 2011;38:263.
40.
go back to reference Budrionis A, Bellika JG. The learning healthcare system: Where are we now? A systematic review. J Biomed Inform. 2016;64:87–92.CrossRef Budrionis A, Bellika JG. The learning healthcare system: Where are we now? A systematic review. J Biomed Inform. 2016;64:87–92.CrossRef
42.
go back to reference National Guideline Centre (UK). Emergency and acute medical care in over 16s: service delivery and organisation. London: National Institute for Health and Care Excellence (UK); 2018 Mar. (NICE Guideline, No. 94.) Chapter 29, Multidisciplinary team meeting. National Guideline Centre (UK). Emergency and acute medical care in over 16s: service delivery and organisation. London: National Institute for Health and Care Excellence (UK); 2018 Mar. (NICE Guideline, No. 94.) Chapter 29, Multidisciplinary team meeting.
44.
go back to reference Wolf A, Dedman D, Campbell J, Booth H, Lunn D, Chapman J, et al. Data resource profile: Clinical Practice Research Datalink (CPRD) aurum. Int J Epidemiol. 2019;48:1740–1740g.CrossRef Wolf A, Dedman D, Campbell J, Booth H, Lunn D, Chapman J, et al. Data resource profile: Clinical Practice Research Datalink (CPRD) aurum. Int J Epidemiol. 2019;48:1740–1740g.CrossRef
Metadata
Title
An informatics consult approach for generating clinical evidence for treatment decisions
Authors
Alvina G. Lai
Wai Hoong Chang
Constantinos A. Parisinos
Michail Katsoulis
Ruth M. Blackburn
Anoop D. Shah
Vincent Nguyen
Spiros Denaxas
George Davey Smith
Tom R. Gaunt
Krishnarajah Nirantharakumar
Murray P. Cox
Donall Forde
Folkert W. Asselbergs
Steve Harris
Sylvia Richardson
Reecha Sofat
Richard J. B. Dobson
Aroon Hingorani
Riyaz Patel
Jonathan Sterne
Amitava Banerjee
Alastair K. Denniston
Simon Ball
Neil J. Sebire
Nigam H. Shah
Graham R. Foster
Bryan Williams
Harry Hemingway
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Medical Informatics and Decision Making / Issue 1/2021
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/s12911-021-01638-z

Other articles of this Issue 1/2021

BMC Medical Informatics and Decision Making 1/2021 Go to the issue