An informatics consult approach for generating clinical evidence for treatment decisions
Creators: name: Lai, Alvina G.
name: Chang, Wai Hoong
name: Parisinos, Constantinos A.
name: Katsoulis, Michail
name: Blackburn, Ruth M.
name: Shah, Anoop D.
name: Nguyen, Vincent
name: Denaxas, Spiros
name: Davey Smith, George
name: Gaunt, Tom R.
name: Nirantharakumar, Krishnarajah
name: Cox, Murray P.
name: Forde, Donall
name: Asselbergs, Folkert W.
name: Harris, Steve
name: Richardson, Sylvia
name: Sofat, Reecha
name: Dobson, Richard J. B.
name: Hingorani, Aroon
name: Patel, Riyaz
name: Sterne, Jonathan
name: Banerjee, Amitava
name: Denniston, Alastair K.
name: Ball, Simon
name: Sebire, Neil J.
name: Shah, Nigam H.
name: Foster, Graham R.
name: Williams, Bryan
name: Hemingway, Harry
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Research Article

description: 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.