An Informatics Consult approach for generating clinical evidence for treatment decisions

Lai, A. G.; Chang, W. H.; Parisinos, C. A.; Katsoulis, M.; Blackburn, R. M.; Shah, A. D.; Nguyen, V.; Denaxas, S.; Davey Smith, G.; Gaunt, T. R.; Nirantharakumar, K.; Cox, M. P.; Forde, D.; Asselbergs, F.; Harris, S.; Richardson, S.; Sofat, R.; Dobson, R. J.; Hingorani, A.; Patel, R.; Sterne, J.; Banerjee, A.; Denniston, A. K.; Ball, S.; Sebire, N. J.; Shah, N. H.; Foster, G. R.; Williams, B.; Hemingway, H.

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, with return of results in clinical timescales. 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. We examined four sources of evidence for the effect of warfarin on stroke risk (efficacy) or all-cause mortality (safety) from: (i) randomised controlled trials (RCTs), (ii) meta-analysis of prior observational studies, (iii) trial emulation (using population electronic health records (N = 3,854,710) and (iv) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems. 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). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61) and ischaemic stroke (HR = 0.27). 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 within clinical timescales.