For most patients suffering from chronic illness and chronic pain, there will have been at least once in their lives when they allow themselves to eagerly anticipate the availability of a new drug treatment. They may have read about in its early stages of clinical development, when investors’ whispers were not whispered enough to avoid the ears of some Wall Street Journal reporter. Or they may have seen it discussed a couple of years before on the evening news.
So, by the time this new treatment, this new hope, is approved for use by the general public, the patient expects that it will be overwhelmingly helpful to the overwhelming majority of patients.
Time for the reality check: Just because a treatment has been found in clinical studies to be impressively efficacious, does not necessarily mean it will be impressively effective.
Efficacy and effectiveness studies each have important roles in the evaluation of an intervention. Unfortunately, many individuals do not understand the differences between efficacy and effectiveness studies. One can think of efficacy as the performance of an intervention under ideal and controlled circumstances; on the other hand, effectiveness refers to that intervention under “real-world” conditions. However, it may be best to consider efficacy trials and effectiveness trials on a continuum, as it is rare to have a perfect clinical study—no matter what the type.
How can an efficacious intervention become effective in clinical practice? In an article in the journal “Hepatology” in 2010, Dr. El-Serag suggested that for an efficacious intervention to be effective in clinical practice, health care providers must identify the appropriate target patient population, make patients aware of the intervention, and patients must accept and comply with the intervention. This does not always happen in the real world. In other words, efficacy research maximizes the likelihood of bringing a treatment effect to light, if one exists; effectiveness research takes into account all the vagaries of the doctor-patient-reception desk interaction: the hurried doctor who does not take time to convince the patient of a given intervention, the patient who does not like to take a pill every day, that nasty person who answers the phone and takes down your phone number wrong so you never have a chance to ask the doctor that one question whose answer may have convinced you to initiate a given intervention.
• An efficacy study asks if an intervention works under ideal circumstances; an effectiveness study asks if an intervention works in the real world.
• An efficacy study takes place in a controlled setting; an effectiveness study takes place in the typical clinical office setting.
• An efficacy study involves a highly-selected population, often excluding concomitant medical problems; an effectiveness study appreciates that patients will have more than one medical problem in many cases, and thus involves a more heterogeneous population.
• An efficacy study has a standardized intervention, and generally will not allow other treatments; an effectiveness study is more flexible, allowing additional treatments if the clinical condition so indicates (for example, a course of steroids if the inflammation of joints is too much to bear in the course of a rheumatoid arthritis study).
Health care providers on the front line have often been frustrated by randomized controlled studies, as patients and their doctors have come to realize that the clinical trials upon which drug approval is based often do not seem to reflect the real world. Hence, the United States has devoted considerable resources to comparative effectiveness research, as I discussed in a prior blog. It is hoped that comparative effectiveness research will assist patients, physicians and policy makers to make health care decisions that improve the medical outcomes of individuals and populations. Effectiveness studies will be the key means of making conclusions that impact the every-day world of patient-doctor interaction.
It remains to be seen whether effectiveness research will prove timely in confirming what is best practice from an original efficacy study. Up until now, such lessons have been a long time in coming, and costly. For example, the rheumatoid arthritis drug anakinra is generally considered by the rheumatology community to not be a very effective drug compared to other agents that have come on the market during the same era. Interestingly, in the American College of Rheumatology guidelines for the treatment of rheumatoid arthritis, last updated in 2012, anakinra is not even included as a treatment option for rheumatoid arthritis. Had anakinra been the subject of effectiveness trials, perhaps it would never have been approved for the treatment of rheumatoid arthritis.
Of course, it is always about evidence-based medicine. But it is also about the basis of the evidence.