Richard J. Martin 1,2, Alison M. Chisholm 2 & David Price 2,3 1. National Jewish Health, Denver, Colorado 2. Respiratory Effectiveness Group, Cambridge, United Kingdom 3. University of Aberdeen, Aberdeen, United Kingdom The Arch Conference Declaration Helping to Further the Science of Pragmatic Research

The Arch Declaration Comprises: 7 papers discussing the key themes of the Arch Summit –the inaugural meeting of the Respiratory Effectiveness Group (REG) Objective: to help move the entire area of pragmatic and observational research forward so it becomes better incorporated into clinical practice decisions for the benefit of patients, practitioners, and other stakeholders

REG: Key Facts (I) An independent, collaborative research and advocacy network set up in 2012/3 to: o Defragmenting activities and unifying experts working in “real-life” (respiratory) research o Raising the quality and profile of the field o Achieving better integration of non-randomized control trial (RCT) data into clinical practice guidelines. Registered as a not-for-profit social enterprise in the UK

REG: Key Facts (II) Unites >80 expert collaborators from >20 countries. Supported by multiple partners and are set by the group’s Management Committee and Research and Advocacy Collaborators. Seeks to partner with established groups and societies who have overlapping and/or aligned goals, including: o The EMA’s European Network of Centres for Pharmacoepidemiology & Pharmacovigilance (ENCePP) o The International Primary Care Respiratory Group’s UNLOCK Committee Website:

REG: founding principles Registration, randomized controlled trials (RCTs) have long been the gold standard in evidence- based research. RCTs: o Pro: Are important & form the basis for national and international guidelines. o Con: Have drawbacks – they deal only with highly selected populations and can offer minimal representation of the true patient populations treated in routine care (≤5% of true asthma & COPD patients 2 2. Herland Ket al. Respir Med 2005;99:11–19.

Heritage of real-life research “Pragmatic trials”: o Studies designed to reflect the real world (patient types and/or ecology of care) more closely than RCTs 4 o Determine the effects of an intervention under the usual conditions in which it will be applied in contrast to the ideal circumstances that are assessed by RCTs 5 4. Schwartz D, Lellouch J. J Chronic Dis 1967;20:637– Thorpe KE, et al. CMAJ 2009;180:E47–E57.

The need for a diversity of approaches “Randomized controlled trials, long regarded as the ‘gold standard’ of evidence, have been put on an undeserved pedestal. Their appearance at the top of ‘hierarchies’ of evidence is inappropriate; and hierarchies, themselves, are illusory tools for assessing evidence. They should be replaced by a diversity of approaches that involve analyzing the totality of theevidence-base” 3 3. Rawlins M. Harveian Oration. Royal College of Physicians, London England. 16 October 2008

Perception challenges Observational study results as “data mining” by: o Journal Editors & Reviewers o Guideline developers BUT Quality methods do exist, e.g.: o a priori analysis planning, o Protocol registration o Statistical methods to minimize possible confounders Ignoring the value of well-designed pragmatic and observational studies can see important safety and effectiveness data being overlooked