How can epidemiology help in clinical practice?

Randomised controlled trials (RCTs) are one of the least biassed sources of evidence and the cornerstone of evidence-based medicine, but involve relatively small numbers of highly selected patients who do not reflect the general IBD population (e.g. pregnant patients and patients with co-morbidities, extensive surgery and stomas of all types are excluded). The in- and exclusion criteria and follow-up protocols are strict and do not reflect routine care. Therefore, the conclusions of RCTs are necessarily limited to patients enrolled in the trials and have limited external validity. In an era in which evidence-based medicine is being promoted, increasing direct health care costs need to be controlled and the subjective perception of health by patients is increasingly valued, epidemiological studies provide essential additional information to clinicians and health care organisations.

Classic epidemiological research has shown that the incidence and prevalence of IBD have increased rapidly in recent decades [1]. At present, more than 5 million people are affected worldwide. Policy makers, insurance companies and health care facilities should be aware of the increasing burden of IBD and its implications for health care capacity planning and budget allocation.

Clinical heterogeneity in the frequency of flares and the appearance of complications and extra-intestinal manifestations is one of the main features of IBD. As described in the ECCO Guideline 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease, there is a trend towards the prescription of earlier and more aggressive maintenance therapies for Crohn’s Disease [2]. Predicting the risk of an unfavourable long-term outcome in an individual patient at diagnosis is thus important in order to prevent under- and over-treatment. At present, molecular markers are not sufficient to stratify patients. Epidemiological cohort studies have shown that presence of perianal disease, an ileocolonic location, a young age at onset, and the need to treat the first flare with corticosteroids are associated with a high risk of disabling disease. These clinical markers are, however, present in a large proportion of patients and their discriminative accuracy is still limited. Future studies with more detailed information in large patient cohorts are warranted.

None of the drugs currently available for IBD are effective for all patients. The long-term response to drug treatment is less than 50% even for the most powerful drugs and all drugs are associated with possible severe side effects. Therefore, novel drugs are being developed and tested in RCTs designed with the aim of proceeding to drug registration. Pharmaco-epidemiological post-marketing studies are subsequently important to provide clinicians with additional information on real world effectiveness and safety. Cohort studies can also identify specific patient subgroups and clinical markers predictive of the risk of adverse effects or primary non-response, thereby facilitating personalised medicine approaches. Furthermore, the dosage and interval in a real-life setting can be assessed and medication cost estimations performed. Since RCTs are costly, the majority focussing on novel drugs are initiated by big pharma companies. Studies investigating treatment strategies or aiming at head-to-head comparison of already available drugs are much less likely to be performed. Novel statistical methods allow quasi experiments with epidemiological data as the best alternative to RCTs. Comparative effectiveness studies have been published comparing early introduction of immunosuppressives and TNF blockers with treatment later during the disease course [3–5]. More recently, comparative effectiveness studies comparing adalimumab with infliximab and infliximab with vedolizumab have been published [6–8]. These studies help to provide information on the potential place of new drugs or strategies in the treatment of IBD. For the correct interpretation of these studies, basic knowledge of pharmaco-epidemiological methods is, however, important [9].

Finally, monitoring and improving the quality of care is a continuous task for every healthcare professional and institution. In recent years it has become clear that the subjective perception of health by patients is an important indicator when assessing quality of care. In this context, systematic registration of not only traditional quality indicators but also patient-reported outcomes (PROMs) and experiences is increasingly implemented. Mounting evidence underlines the importance of patient empowerment and tight monitoring to improve the long-term outcome of IBD. Against this background, remote monitoring of PROMS with telemonitoring systems has been studied and validated [10, 11]). Remote monitoring is now done in routine care in many centres across the world. Through digitalisation in health care and the systematic use of electronic health records in most hospital information systems, the systematic registration of quality indicators in the primary care process is also increasing. It is increasingly being recognised that through analyses of all data combined, new insights emerge that can improve the decision-making process in healthcare. Conversion of data into information can result in improved patient stratification, personalised care pathways, better management within the organisation and better services. Since health-related information is sensitive, processing of data must always have a correct ethical context and be done in conformity with the general data protection law.

In summary, epidemiological studies in IBD have revealed the increasing global burden of IBD, helped to improve patient stratification and identified markers to predict the disease course and response to treatment. Pharmaco-epidemiological studies are necessary to provide information about real world effectiveness, safety and cost-utility and to define the place of novel drugs in treatment algorithms. With the digitalisation of health care, increasingly detailed data relating to large patient cohorts will become available for epidemiologists. Provided that protection of the privacy of health care customers and the ethical and juridical context are taken into account, merging and analyses of all these data is an exciting strategy that can lead to new insights and improve the decision-making process in healthcare. 

References

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2. Gomollón F, Dignass A, Annese V, et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 1: Diagnosis and medical management. J Crohn’s Colitis 2017;11:3–25.
3. Chatu S, Saxena S, Subramanian V, et al. The impact of timing and duration of thiopurine treatment on first intestinal resection in Crohn's disease: national UK population-based study 1989–2010. Am J Gastroenterol. 2014;109:409–16.
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7. Singh S, Heien HC, Sangaralingham LR, Schilz SR, Kappelman MD, Shah ND, Loftus EV. Comparative effectiveness and safety of infliximab and adalimumab in patients with ulcerative colitis. Aliment Pharmacol Ther. 2016;43:994–1003.
8. Allamneni C, Venkata K, Yun H, Xie F, DeLoach L, Malik TA. Comparative effectiveness of vedolizumab vs. infliximab induction therapy in ulcerative colitis: experience of a real-world cohort at a tertiary inflammatory bowel disease center. Gastroenterology Res. 2018;11:41–5.
9. Targownik LE, Suissa S. Understanding and avoiding immortal-time bias in gastrointestinal observational research. Am J Gastroenterol. 2015;110:1647–50.