Absolute Risk Reduction: Your Secret Weapon in Literature Evaluation
If you spend any amount of time looking at clinical studies or doing literature evaluation, you’ll see the term Relative Risk thrown about liberally. You’ll also see things like Odds Ratio, and Hazard Ratio on the regular.
But you know what you won’t see all that often?
The unsung hero of literature evaluation: Absolute Risk Reduction (ARR).
It’s hard being Absolute Risk
It’s actually pretty rare (especially in my world of oncology) to see Absolute Risk Reduction reported in a study. You’ll find that you have to calculate it for yourself. But if it’s so important, why do you have to manually calculate it for most studies? Why isn’t it reported with the findings?
Simply put, Absolute Risk is less sexy than Relative Risk. It doesn’t make for good press headlines. If Absolute Risk is the Jan Brady of the research world, Relative Risk is its Marcia. In the world of press releases, Relative Risk is the younger, more attractive cousin of Absolute Risk.
Luckily, your literature evaluation skills don’t have to be hampered by a lack of reporting. Today I’m going to give you the best tool to separate the clinical wheat from the chaff. I’m going to teach you the absolute risk reduction formula and show you how to calculate absolute risk reduction.
Simply put, Absolute Risk Reduction is the only way to identify the true context of something reported in a clinical trial. It’s usually a much smaller number than Relative Risk Reduction (RRR), but it helps you assess the real world impact of a study finding.
And even if you don’t care about any of that, I can assure you that you’ll need to be able to calculate absolute risk reduction for the NAPLEX and any BPS exam you may have in your future.
So let’s dig in…
What is Absolute Risk Reduction?
Allow me to present our friendly mascot for today's lesson, the ARR Pirate:
The ARR Pirate (do you see what I did there?)
Look at him. So vigilant. Ready at a moment's notice to introduce you to the business end of his fist. Think of this little guy whenever you read a new study or journal article. Let him be your conscience and guiding light.
Absolute Risk vs. Relative Risk
Time for some vocabulary. The Absolute Risk is the total risk of a given 'thing' occurring after all risk factors and confounding variables are summed up. For example you could sum up your lifetime risk of having and atherosclerotic event based on the incidence and prevalence of your demographic.
Relative risk is different. It's the risk of a given 'thing' in comparison (ie. relative) to something else. For example, your risk of developing a DVT if you're a smoker compared to if you weren't a smoker.
When we talk about Relative Risk Reduction (RRR) and Absolute Risk Reduction (ARR), we're talking about an intervention. We're reducing the absolute and relative risk by giving some treatment. The absolute risk reduction is the total reduction in risk that results by choosing a given treatment. This number is often very different from the relative risk reduction.
With RRR, the reduction of risk is compared to some other group. You could compare the effectiveness of Entresto in reducing mortality from heart failure to an existing treatment like enalapril. Or you could compare Paxil CR to no intervention (placebo) at reducing symptoms of depression.
Great. So what does all of that mean to you as a clinician?
You can have a lot of fun with relative risk…
For example, let’s say that I’m afraid of flying (not because of COVID, I’m just scared of dying in a plane crash). To mitigate that fear, I could choose to no longer fly in planes. Doing so would drop my relative risk of dying in a fiery plane crash to almost zero. We’d be comparing the relative risk of the following:
Me dying in a plane crash assuming I travel via plane
Me dying in a plane crash assuming I do not travel via plane
By choosing NOT to fly in planes, maybe my relative risk of dying in a plane crash would be somewhere around 99.999% (because a fiery plane could crash into me while I'm doing yard work or something). That’s a HUGE reduction, and a very attractive number. Wouldn’t you want to reduce your risk of dying in a plane crash by 99.99%?
But you have to ask yourself…what is the baseline risk of dying in a plane crash (even if you DO fly in planes)? We have access to this data, and your absolute risk is 0.000009%. A 99.999% reduction from 1 in 11 million isn't nearly as headline worthy, is it? Can you imagine imagine an ad for this when you’re scrolling through you IG feed?
“Man uses this 1 SIMPLE TRICK to reduce his risk of dying in a plane crash by 0.000009%”
Not very exciting. Much less sexy than 99.99%.
Let's keep going with the heart failure medication Entresto. You have a study that shows a 19.4% relative risk reduction of cardiovascular death in heart failure patients using Entresto compared to enalapril. If you were practicing a few years ago when it first came out, you probably saw news stories boldly claiming that Entresto reduces your risk of death by 20% (because rounding). If you were to look at those studies and calculate absolute risk reduction, you’d find that it was 3.2%.
3.2% mortality reduction for a disease as common as heart failure is nothing to sneeze at (this study was actually stopped early due to the benefit seen in the Entresto group). But you probably don't need me to tell you that 3.2% is wayyyyyyyy less than 20%.
And that's what we're driving at with absolute risk here. It helps to lend you perspective to the equation.
How to Calculate Absolute Risk Reduction
Relative Risk Reduction is not a bad guy. He's just misunderstood. At the end of the day, RRR and ARR are just different ways to measure the size of an intervention. They're a way to help you determine the clinical usefulness of a drug. They can both help you decide if new treatment X will be beneficial to your patient.
But there's a reason I’m writing this article. As I said above, you typically have to calculate absolute risk reduction, because it’s not reported for you. Relative risk is sexier, and it doesn’t always translate into a phenomenal clinical benefit. Also, in the medicine world, sexy also tends to mean "cripplingly expensive." Absolute risk reduction is absolutely required if you want to do any kind of cost-benefit analysis.
So what is the Absolute Risk Reduction Formula?
Let's go back to our Entresto study. And let's zero in on that cardiovascular death rate part. You'll see that in the control group (enalapril), 16.5% of the patients died from cardiovascular causes. In the experimental group (Entresto), 13.3% died from cardiovascular causes.
Absolute Risk Reduction is the control event rate (CER) minus the experimental event rate (EER).
CER - EER = ARR
0.165 - 0.133 = 0.032
Or as we mentioned above, 3.2%. If you're doing this with a study (or test question) that doesn't give you the percentages you'll have to manually calculate them from the study. So if 800 patients in a control group of 1000 people had an event, your CER is 80% (or 0.80).
The relative risk reduction formula there is also pretty simple:
(CER - EER) / CER = RRR
(0.165 - 0.133) / 0.165 = 0.1939
Or (also as we mentioned above), 19.4%.
You'll notice that we're converting percentages to their decimal forms to carry out these calculations. This is a best practice that will prevent you from making any decimal point errors. It's also necessary to work in decimal form in order to calculate the Number Needed to Treat (NNT).
No discussion of absolute risk reduction is complete without mentioning the number needed to treat. The NNT is just another way of expressing the ARR. The number needed to treat is the number of patients you have to treat in order to prevent one 'event.' An event in this case would be cardiovascular death from heart failure.
NNT is the inverse of ARR.
1 / ARR = NNT
Using our Entresto numbers...
1 / 0.032 = 31.25
The NNT would be 32 in this case. Why 32? Because the number needed to treat is always a whole number (an integer). You can't treat 0.25 of a person. So whenever your number needed to treat ends in a decimal point, round up to the next whole number.
To apply this in "real terms," you'd need to give Entresto to 32 patients before you prevented one cardiovascular death.
How to Use Absolute Risk Reduction to Make Clinical Decisions
You should use ARR, NNT, and even the RRR to determine if an intervention is worth it for your patient. As you've seen here, you can very easily calculate ARR and NNT. You’ll use this information on top of the criteria that you already use in your evaluation. When you're weighing treatment options for patients, calculate ARR for a few different choices. Look at what the drug is going to cost the patient. Look at the dosing schedule and determine if adherence will be an issue. Look at drug interactions and any other relevant pearls for each individual drug in a class.
Then you can bring this information to the patient and the medical team and make a collaborative choice that is best for the patient. When everybody is involved (especially the patient), everybody wins.
And again, you’re gonna need all of this info for your NAPLEX and BPS exams. So if being an awesome clinician isn’t motivation enough for you, then let necessity drive your decision to get as comfortable with this as possible.
In closing. When you're in doubt. Just think of what the ARR Pirate (and his judgmental glare) would do.
