Randomized, placebo-controlled Phase III clinical trials (or RCT’s for short) traditionally have been considered the gold standard for evidence in the pharmaceutical industry. The entire industry value chain–from regulatory submission to sales rep interaction in physician offices–has been built around the importance of this type of clinical trial. But in a world that is changing dramatically due to technological innovation, is this standard outdated? Just as we now use GPS on our smart phones instead of paper maps, is it time to upgrade our approach to how we evaluate our medicines?
“Real world evidence allows payers to arm themselves with fact-based arguments to pharmaceutical companies to ensure they are receiving sufficient value”
RCTs–A good Place to Start, with Caveats
There is a long list of well recognized advantages of randomized, placebo-controlled studies. Among these include a universally accepted scientific standard, and a means to eliminate bias to measure the effectiveness (efficacy and safety) of a medicine. But no methodology is perfect. For example, strict exclusion criterion for patient enrollment usually results in many patients with relevant comorbid diseases not being included in the trial. However, a patient with comorbid disease is a common issue that physicians deal with daily in clinical practice. Therefore, the clinical trial evidence may be of limited value to physicians in this “real-world” situation. RCTs are also expensive and there are limits to how many patients can be enrolled. So it is highly possible that the effectiveness of a medicine for certain sub-populations is not captured.
A Better Mousetrap?
Real world evidence addresses many of the limitations of RCTs. First of all, as the name suggests, it takes place in a real world setting. So information may be “messy,” but this is actually a better reflection of true clinical practice. It is analogous to the theoretical download speeds that are advertised by cable companies. If the purported speed becomes only half as fast when my neighbor is also on the Internet, wouldn’t I want to know that as a consumer?
Second, due to the accessibility of electronic medical records, the amount of clinical data available is much greater than exists in most Phase III clinical trials. This preponderance of information helps confirm (or cast doubt on) the benefits of the medicine much more quickly and robustly. This is better for both patients and their doctors.
Scientific vs. Economic Theory
The debate over the best methodological approach most likely will not be settled by scientists, but by another academic discipline altogether: economics. Today’s medicines are expensive and payers want to be sure that they are receiving value for money. The initial assessment of value can be done based on RCTs, but ultimately it is real world evidence that will justify the effectiveness of a medicine within a payer’s patient population. If the effectiveness of a medicine does not justify the price, then pharmaceutical companies should expect payers to demand prices that better reflect the real world value provided by that medicine.
What’s a Company to Do?
Companies will have conflicted thoughts about how to deal with real world evidence. Some R&D leaders dismiss it as being an inferior evidence standard to RCTs. However, what pharmaceutical companies think about real world evidence may be irrelevant. Payers are now gaining knowledge from real world evidence. The Internet has changed how we negotiate car prices by changing the asymmetry of information that had existed before: real world evidence allows payers to arm themselves with fact-based arguments to pharmaceutical companies to ensure they are receiving sufficient value. Pharmaceutical companies will ignore this technological change at their peril.