Steph’s Note: This week, we’re building on our previous journal club post with this discussion about evidence-based medicine (EBM). Bringing her enthusiasm for this topic is a new guest poster, Dana DelTufo, PharmD.

Dana DelTufo is a newly graduated pharmacist (well...technically not until she's licensed, but the super expensive piece of paper has been awarded) from Notre Dame of Maryland University School of Pharmacy in Baltimore, MD. She is an incoming PGY-1 pharmacy resident at Meritus Medical Center and wants to specialize in medication safety post-completion. Her professional interests include medication safety, cardiology, and infectious disease. Her personal interests include cooking, going on hikes, photography, and Zentangle (look it up and thank her later). She has been using tl;dr pharmacy religiously for the past three years and can't wait to write more articles. You can say hi to Dana on LinkedIn or Twitter @DDelTufoRx.

What is evidence-based medicine?

Do you have the common cold? Have some chicken noodle soup! Did you fall and scrape your knee? I bet a kiss from mom will magically heal it! Do you have a cough? Eat a teaspoonful of honey! While these may be some tried and true home remedies that have been passed down over centuries, they’re not exactly what we call evidence-based medicine. Sorry, I don’t make the rules here!

Evidence-based medicine (EBM) can be looked at as a simple equation, which isn’t something we’re used to as pharmacists (I hope you have that Cockcroft Gault equation memorized).

EBM = clinical expertise (that’s you!) + patient values + best available evidence.

Not so bad…right? Let’s break it down even more.

What is evidence? Evidence is the result of patient-centered clinical research that is relevant to your patient. Not your friend’s patient, not your preceptor’s patient, not your brother’s friend’s cousin’s mother-in-law’s goldfish’s patient (thankfully goldfish will never be practitioners, but you get my point). The information you are researching has to apply to your patient as best as humanly possible, such as baseline characteristics, comorbidities, treatment setting (e.g., hospital, outpatient, nursing home, etc.), and disease state in question - just to name a few. Because medicine doesn’t follow a “one size fits all” methodology (even though that would make our lives sooo much easier), you’ll rarely find a study that fits your patient perfectly.

Err…I said goldfish can’t be practitioners, but what about lobsters? Kidding! (Image)

This is where the clinical expertise comes in!

As someone who has just graduated pharmacy school, I often think to myself, “Am I supposed to have clinical expertise?” I don’t have it yet, but I’ll be working with so many people who do!

Clinical expertise is insight and intuition acquired by a seasoned clinician (btw, it’s frowned upon to ask people if they’re seasoned) through extensive interactions with patients and seeing the outcomes obtained from various interventions. Experience is important when there’s limited or lack of scientific evidence.

A great way to build your own clinical expertise is to work closely with people who do have it and to use your pharmacy school skills. For four years, we’re taught vital clinical information for when we’re out in practice, but we were also taught how to find the most reliable and up to date information (Get it? UpToDate? No? Okay…).

Basically, what I’m trying to say is if you don’t have your own clinical expertise, you have experienced coworkers and valuable resources at your fingertips.

Now for the bread and butter of the equation…the patient and their values! We see patients day in and day out, but we never truly know exactly what they go through on a daily basis. Patients’ values and what’s important to them should absolutely be involved in any patient care plan you ever take part in. If it doesn’t matter to the patient, does it even matter at all?

A patient’s values can include subjective beliefs, attitudes, cultural factors, and spiritual beliefs that affect their healthcare choices. These values can be a huge influence on your patient’s care because they determine your patient’s desire to avoid certain bad health outcomes or influence their willingness to undergo a specific treatment option. Without input from patients about their beliefs and desires, clinicians run the risk of doing things to their patients rather than for their patients. The goal is to keep our patients happy and healthy, and evidence-based medicine will help us get there (I promise!).

Why Is It Important to Learn EBM?

Contrary to how you may feel during pharmacy school, there is a reason why it’s important. As a pharmacist, you are going to get bombarded with more questions than you could ever imagine. Most of the questions will require you to do a little bit of research to find an accurate answer, or you’ll need to use the famous, “I’ll look it up and get back to you” line.

You aren’t expected to know everything and shouldn’t feel ashamed if you have to look something up for a provider, for example. More likely than not, the provider will appreciate your efforts instead of wondering why you didn’t know the answer right away. Proficiency in EBM can help pharmacists make more valid and reliable recommendations. If you want your recommendation to be accepted and implemented during clinical rounds, it will be easier to convince the team when your recommendation is based on principles of EBM.

Pharmacy is constantly evolving on a daily basis, which is what drew me to it in the first place. I’m sure you’ve heard of the common saying, “Pharmacy school is like trying to drink from a firehose.” There is no possible way for pharmacists to keep up with every single new piece of literature that comes out (unless one day becomes longer than 24 hours). In 2019 alone, there were more than 315,000 new citations added to PubMed. Just last year, there were 53 new drugs approved by the FDA.

My head is spinning just from typing this data!

Knowledge keeps pharmacists in tune to what’s going on in the world of medicine that is comprised of a large pool of information. EBM is a useful way to incorporate research-based findings into clinical practice and to provide education to others along the way…unless you work with someone who has read every single research article in the world.

How to Practice EBM

The above information was nice, but how do I actually practice EBM? Now is the time to introduce you to the 5 A’s! (I certainly wish my grades looked like that…but anyway…) The 5 A’s are a helpful way to remember the critical steps of practicing EBM. In the end, following the 5 A’s will increase the likelihood of a favorable outcome.

ASK an Answerable Question

This might seem obvious, but I’ve come across so many questions that seemed almost impossible to answer just because of poor wording or not enough detail. Which of the following questions sounds better to you? (Take advantage of this…this will probably be the easiest question that you answer for the rest of your career.)

What is the best treatment for heart failure?
In elderly patients with systolic heart failure, do ACE inhibitors reduce mortality in comparison to placebo?

If the first question left you scratching your head, then you’re on the right track. There just wasn’t enough detail to be able to answer that question. The best treatment for whom? What type of heart failure do they have? Are they already on treatment for heart failure? What other medications are they taking? Do they have any allergies? So… many… questions…

A well-formulated question shouldn’t leave you with even more questions. The second question is clearer, more concise, and provides you with enough information to be able to look up the most accurate answer. If you haven’t gotten it by now, B was the correct answer. You can go celebrate 100% responsibly, but come back in five minutes.

We aren’t done here!

You can formulate an answerable clinical question of your own by using yet another acronym, called PICOTS. PICOTS stands for patient population, intervention, comparator, outcome, timing, and setting.

P: Define the patient population that will be studied in the trial and consider how it compares to the general affected population.
I: Define the intervention, including all of its components.
C: Define whether there is a placebo or active control comparator.
O: Define the safety and effectiveness outcomes that matter to patients and which predict long-term successful results.
T: Define the duration of treatment and the follow-up schedule.
S: Define the setting (primary, specialty, inpatient, nursing home, or other long-term care setting) where the study is implemented and the relevance of the study setting to real world use.

So, how do you use PICOTS?

Through my experiences, it’s helpful to know the type of question that’s being asked. The common categories include intervention/therapy, diagnosis/diagnostic test, etiology, prevention, and prognosis/prediction. Here are some fill in the blank template examples to help make sure you cover all of your bases for different types of questions:

a. Intervention/Therapy: In ___________ (P), what is the effect of ___________ (I) on __________ (O) compared with __________ (C) within ____________ (T)?

b. Diagnosis/Diagnostic Test: Are/is ___________ (I) more effective in diagnosing ___________ (P) compared with ____________ (C) for ___________ (O)?

c. Etiology: Are _________ (P) who have ___________ (I) at ______ (increased/decreased) risk for/of _________ (O) compared with ___________ (P) with/without __________(C) over _________ (T)?

d. Prevention: For _________ (P) does the use of _________ (I) reduce the future risk of _________ (O) compared with __________ (C)?

e. Prognosis/Prediction: Does ________ (I) influence _________ (O) in patients who have ________ (P) over _________ (T)?

As you can see, each question doesn’t require the use of all letters in the acronym, although using all of them ensures a more answerable question. When using the letter S for setting, it’s up to you to make sure the setting of the study or clinical paper applies to the setting in which your patient will be treated. Practice makes perfect when using PICOTS so try to use this method as much as you can.

I found this useful during my acute care rotation when I was asked up to ten DI questions per day. Re-wording the question in a way that fits the PICOTS method really helped me streamline the appropriate resources to find the most accurate answer.

ACQUIRE Applicable Information

Of course, it’s best to use reliable resources when acquiring information to answer your question. You want to use primary or secondary literature as they will provide you with respectable clinical information. Primary literature can be in the form of original clinical trial reports that can be found in medical journals or clinical guidelines. Some examples of secondary literature include PubMed, Cochrane Library, Embase, and Google Scholar.

Don’t catch yourself referring to Wikipedia as a reputable resource. Your preceptor will NOT be pleased with you!

The type of question that you’re trying to answer may have some favored research study designs that will aid you in finding an elite answer. Table 1 here will be beneficial in narrowing down your search.

So, we have our question. We’ve completed our search, but there are 98,534 results. Like I said before, you’d be able to sort through all of those articles if there were more than 24 hours in a day, but thankfully most databases have a filter function. You can use filters to narrow your search even further.

This is why you want an accurate idea of your patient so that you can use those filters to match their specificities (i.e., age, gender, etc.). Hopefully, you’ll end up with a less scary number after your filters are applied. If not, maybe try to start a new search and use different key words for a more streamline approach.

APPRAISE the Search Results

Critical evaluation and appraisal are a very significant part of the research process. You need to make sure you can identify where the information came from, its validity, and how relevant it is to your particular context. In other words, is the information valid and clinically useful?

Not all articles you come across are going to be useful (sorry, not sorry), so having a keen eye will guide you through the weeds so to speak. Using unreliable evidence in practice could lead to harm involving your patient or a pricey medical malpractice lawsuit.

Research evidence is appraised using three categories: validity, importance, and applicability to the patient. Developing these critical appraisal skills involves learning about which questions to ask in order to determine an article’s validity. You can read more about this in tl;dr pharmacy’s brilliant biostatistics articles (try to say that three times fast!).

In general, trials that provide high strength of evidence…

Study patients who are likely to be offered the intervention in everyday practice.
Examine clinical strategies and complexities that are more likely to be replicated in practice.
Measure the most relevant set of benefits and harms.
Have low risk of bias.
Have adequate power to address subgroups.
Directly compare interventions.
Include all important intended and unintended effects including adherence and tolerability.

APPLY the Information

Once you have found evidence in support of your clinical question and determine its validity, you must then apply it to your situation. The evidence that you find should be appropriately disclosed to your patient in order to allow them to make an informed decision. This approach allows a therapeutic alliance to be formed between you and the patient and is consistent with the principles of EBM.

Remember that easy equation from before? This is that patient values part. Yay for tying everything together!

Here are some questions you can ask yourself based on the type of question you are researching. For questions about…

Diagnosis: Is the test affordable, accurate, and available in my hospital? Can I estimate the pre-test probability of the disease in question? Will the post-test results affect my choice of treatment?
Therapy: Is my patient so different from those in the study group that the results can’t be applied? According to the study results, how much would my patient benefit from the treatment?
Harm: What is my patient’s risk for adverse effects? Are there any interactions with their other medication(s), allergies, or other comorbidities? Are there alternative therapies?
Prognosis: Is my patient similar to the patients in the study group? How will the evidence influence my choice of treatment?

When you are applying the evidence to a real-life patient, you need to take cost and treatment availability into account. Wouldn’t it be silly to recommend the best treatment just to find out that it isn’t even available? Don’t be that pharmacist, or you’ll put yourself back at square one; I’m sure all of this research has you exhausted by this point.

We have one more A to get through, but we’ve gotten through the tough parts by now so hang tight.

ASSESS Your EBM Process

As with any process, it is important to assess its success. We need to evaluate our approach at frequent intervals so that we don’t keep making the same recommendation just to achieve suboptimal outcomes. If the recommendation seems to be failing or wasn’t the best choice to begin with (hey, it happens), this is where working with an interprofessional team is ideal. The team will have different views of the problem and may be able to spark an idea for you.

We need to ask whether we are formulating answerable questions, finding good evidence quickly, effectively appraising the evidence, and integrating clinical expertise and patient’s values with the evidence in a way that leads to a rational, acceptable management strategy.

Here are some other questions to consider:

When you applied the diagnosis or treatment, was it successful? How does your practice site evaluate or audit whether or not interventions are successful?
Has any new data been published in the literature?
How can you improve your clinical decisions?

The tl;dr of EBM

Now that you have a better idea of what evidence-based medicine is and how to use it for your patients, I hope that you’ll try to get some practice with it. If you’re bored one Friday night, you can have your friends or colleagues ask you a random medical question and then try to re-formulate it using PICOTS (sounds thrilling, I know).

EBM isn’t easy, but I know you smarty pants pharmacy people can handle it and can use it to build your clinical expertise. Your patients are depending on you!

Evidence-Based Medicine for Pharmacists