5 key principles

What types of evidence are most useful for supporting you as a physician on a day to day basis?

Can randomized controlled clinical trials (RCT) help you in making the right choice for the patient who sits in front of you? Yes, of course, RCTs are the gold standard in helping to accurately predict the effects of an intervention. A vital first step, however highly beneficial to complement this with real life insights on how the intervention is working in clinical settings, just like yours.

You may wonder, should we rely solely on RCTs because they are randomised and well controlled, or look to real-world evidence (RWE) because it replicates your clinical setting, including all the factors that may influence the outcome? The arguments have been aired extensively on both sides, but we believe the answer is in the middle – RWE and RCTs used together can be the Best in Both Worlds.

In these short articles, we will introduce the fundamental principles of RWE and explore the role of RWE in allergy immunotherapy to enhance decision making alongside RCTs.

Real world data (RWD) is information collected on patients in a real-life setting, in real clinical practices, just like yours. RWD can be sourced from a range of places, e.g. prescriptions, diagnosis codes, hospitalisations or insurance claims. This means that RWD will have the variety of lifestyle factors, medical histories and comorbidities you also see in your patients. This can make for a very diverse data set, however it is very accurate given it’s a slice of the real world.

Real world evidence (RWE) is evidence derived from the appropriate analysis & synthesis of RWD. What may seem like a natural weakness in RWD – a diverse, non-randomised, somewhat chaotic data set – becomes the strength of RWE. This is because it includes all the noise seen in real life, which means it acts as a very good predictor of how an intervention performs under the stresses and complexities of normal clinical practice like yours. Additionally, you can include larger groups of patients for longer periods of time allowing for a range of endpoints that can’t be studied in more restricted RCTs.

At ALK we are committed to bringing the valuable insights RWE can offer to the world of allergy immunotherapy.

It has long been observed that there can be a difference between the efficacy captured by RCTs and the effectiveness seen in a real clinical practice like yours. This is often referred to as the efficacy-effectiveness gap. There are multiple causes of these differences, from the range of patient types to variations in compliance and adherence and other influencing factors such as medical history and environmental factors.

What you will notice about these rather annoying “things” is that they are actually representative of everyday life for everyday patients like yours, with each patient having their own set of personal factors that influence how the intervention might perform for them.

This is why having an understanding of both efficacy and effectiveness is key to making the best decision for real-life patients who live in the real world.

We acknowledge the importance of bringing real life insight to RCTs, supporting your decision making.

In addition to helping you understand the efficacy-effectiveness gap, RWE can provide many additional important insights which RCT studies can not directly deliver.

Due to the way RWE studies can use data from an established source, e.g. insurance claims data, both the study size and follow up period can both be considerable. The financial and ethical limitations of RCT limit both of these dimensions to smaller, shorter study protocols.

The non-randomised and uncontrolled nature of a RWE study limit the ability to derive causative conclusions. However, the sample size, study length and breadth of data mean RWE can provide key evidence for new hypotheses around disease progression, long term outcomes, safety and lifestyle factors.

Lastly, precise measurement of healthcare utilisation costs, both direct such as hospitalisations and drug usage, and indirect, such as working days lost can be measured in real terms.

All of the above are real questions you may have about AIT, we do…

In order to keep the potential usefulness of RWE intact, good principles of evidence based medicine (EBM) should always be followed. Starting with the study design, where in particular, we must ensure cohort groups are comparable to avoid treatment selection bias. But similarly with statistical analysis through to publication writing and public critique. All usual standards of EBM need to be addressed.

Extensive guidelines exist that give detailed rules for RWE studies, practice and handling, e.g. ISPOR.  However, the key idea is to do everything possible to manage the predictable issues found when dealing with non-randomised data; to be publicly transparent and self critical about methodological issues and limitations that may not have been eradicated from the study. This approach is designed to minimise the risk of inappropriate conclusions being drawn.

By following these quality principles we will ensure that the real data, relates to real evidence and can be trusted to form useful insights on real patients just like yours.

Allergy immunotherapy has evolved significantly over the last decade, triggered by the need for more evidence-based medicine. ALK worked with the allergy community to develop the fields’ most robust clinical program, enrolling over 22,000 patients, enabling prescribing decisions to move from experience-based to evidence-based. But as we know, RCTs alone can only tell you so much.

That’s where our REWEAL program comes in. Comprising patient data from independent sources across multiple countries, REWEAL will bring you the best-in-class real-world evidence. We are aiming to confirm the true benefits of AIT– by revealing the effectiveness of AIT in the real world and expanding beyond the follow-up period seen in most RCTs to further investigate a range of relevant outcomes such as asthma exacerbations, drug burden and even progression.

Our goal is to help inform the right treatment decision by providing you with the best in both clinical and real-world evidence.

REWEAL – Real patients. Real questions. Answered.