Informed decision making with patients typically relies on evidence from clinical trials that describe the likely benefits and toxicities. However, patients treated in everyday practice tend to be older and more frail, to have poorer function and performance status, and to have more comorbidities and less social support than those selected to participate in clinical trials. Thus, generalisability to typical patient populations treated in daily practice is often limited. Kennedy-Martin et al explored the generalisability of RCTs in cardiology, mental health, and oncology by assessing studies comparing participants in such trials with those in everyday clinical practice. Patients treated in everyday clinical practice tended to be older, were more often women, and had more comorbidities; 71% of studies concluded explicitly that RCTs were not broadly representative of real-world patients, in particular, pregnant and lactating women are a very large population that is often entirely unrepresented in clinical trials. Furthermore, patients enrolled in trials were treated according to guidelines more often and received more in-hospital procedures. Strict selection criteria for RCTs meant that participants were at a much lower risk of adverse events compared with patients treated in clinical practice.
 
If the efficacy-effectiveness gap means that patients are being given inaccurate information about the potential benefits and risks of treatments, then decisions made using that information may be being made without valid informed consent, disrespecting patient’s autonomy and putting them at risk of avoidable harm. The efficacy-effectiveness gap also raises important issues regarding justice; if resource allocation decisions, including which treatments are funded, are made using evidence that is biased by the efficacy-effectiveness gap, then those decisions will also be flawed, with potentially wide implications for patients. Ultimately, the efficacy-effectiveness gap undermines the gold standard status of RCTs, and actually suggests that it would be unethical to continue with such a flawed representation of real-world effects on patients. Increasing use of RWE is one important way to fill the efficacy-effectiveness gap and augment the evidence from RCTs. This should not be seen as dropping the gold standard, or diminishing the standard of evidence required; rather, enhancing and supplanting RCT evidence with RWD can instead be viewed as reinforcing the gold standard with platinum plating.
 
Source: Section 4.2 (Ethical arguments for incorporating more RWE) of the CIOMS Draft Guidance – Real-World Data and Real-World Evidence in Regulatory Decision Making (6 June 2023)