Blue pill versus red pill: what is the number needed to treat?

Recently I read an article in The New York Times that highlighted some of the important information that drug ads often fail to disclose. As illustrated in the tweet below, the part that really got my attention was that it drew attention to the fact that drug ads rarely discuss the number of patients who need to take a drug before a benefit can be seen.

In health care, we call this the number needed to treat (NNT), a concept that helps us describe the effectiveness of a treatment in practical terms. Even the most effective therapies will only benefit a fraction of the patients that receive it. For others, a therapy may have no effect at all or it may even be harmful. In the latter case, the number needed to harm (NNH) describes the number of patients who need to receive treatment before one of them is harmed by it.

When I teach students about analyzing a clinical trial, I emphasize NNT and NNH as being two of the most important concepts to understand, as they support clinical decision-making and aid in communicating to patients the relative benefits and harms of a treatment. The Times article was the first time I had seen this concept outside of the biomedical literature, and it occurred to me how valuable it would be if non-health professionals knew how to determine NNT/NNH and interpret what it means to patients.

Determining the Number Needed to Treat
To determine NNT, there must be a difference between the treatment and placebo (or the alternative treatment if two treatments are being compared), and it has to be statistically significant – a term used to describe when the difference is not likely a result of random chance. Pharmaceutical manufacturers must demonstrate this before they can claim a drug is effective. The NNT can then be calculated in three simple steps:

  1. Determine the event upon which the trial is based (for example, a reduction in the number of heart attacks). Subtract the percentage of patients who had an event despite receiving treatment from the percentage of patients who had an event while receiving placebo (or the alternative treatment). This is known as the absolute risk reduction (ARR).
  2. Divide 1 by the ARR.
  3. Multiply the resulting number by 100%. This is the NNT.

Here is a practical example:

NNT

The NNH can also be calculated using the above steps, except that the events used are the harms observed in the two groups.

Interpreting the Number Needed to Treat
The ideal NNT is 1, meaning that every patient who receives treatment obtains benefit. This is extremely unlikely, so the closer the NNT is to 1, the better. That being said, there are several important considerations for interpreting the NNT, especially when comparing it to other therapies.

Comparing Outcomes
Not all outcomes upon which the NNT is based are equal. The benefit associated with the NNT depends on which outcome was studied in the clinical trial. For example, let’s say the administrator of a health plan is comparing two drugs for blood pressure to determine which to add to the prescription drug benefit. The first drug has an NNT of 50 for preventing one stroke whereas the second drug has an NNT of 25 for reducing blood pressure by 5 mmHg. Although the second drug has a lower NNT, the outcome for the first drug is more compelling.

The same thing goes when comparing NNT and NNH. If a drug has an NNT of 25 for preventing one heart attack and an NNH of 25 for causing one nosebleed, the benefits of the drug likely outweigh its risks in most patients.

Duration of Time to Observe Benefit or Harm
The duration of clinical trials vary. Some trials are completed in under a day whereas others take years. When a benefit is observed in a clinical trial, it must be interpreted in context with how long the trial was conducted. For example, if the trial for a drug was conducted over the course of 5 years and an NNT of 20 to prevent one death was observed, then it is generally assumed that 5 years are required for the benefit to emerge. However, if a new drug is discovered that demonstrates the same NNT after only 1 year, it likely exerts greater overall benefit because it required less time to match the NNT and additional benefits are likely to accrue over time.

Prevalence of Disease in the Population
From a public health standpoint, the potential impact of a treatment may also depend on the population prevalence of the disease it treats. For example, let’s say one drug treats a rare disease and demonstrates an NNT of 25 in a clinical trial. However, because only 1000 people will get the disease annually, only 40 patients will likely benefit from the drug each year. On the other hand, a drug used for heart attacks may have an NNT of 100. Although its NNT is larger, the number of people who have heart attacks approaches 800,000 annually, meaning that 8000 patients may obtain benefit each year.

Conclusion
Understanding how to determine and interpret NNT/NNH could benefit a wide range of people. Health reporters could use this information to help explain the potential benefits and risks of a new therapy to their target audience. Government officials could use it to determine funding priorities for public health initiatives. Finally, it could help the public discern from drug ads what benefit is being purported as well as the likelihood of obtaining it.

It is hard for me to see a down side, so what if we required pharmaceutical manufacturers to report it?

Agree? Disagree? Have ideas for other important considerations related to NNT/NNH? Please feel free to leave comments below!

Food deserts: how choice is a myth for many

If you are what you eat, then how does your access to healthy food options affect your overall health?

Last week Dr. Heval Mohamed Kelli and colleagues presented research at the American College of Cardiology 2016 Scientific Sessions demonstrating a link between living in a “food desert” and having an increased risk of cardiovascular disease (CVD).1,2 Food deserts are areas of the country where residents have limited access to affordable healthy food options such as fresh fruits and vegetables. Although definitions vary by study, most include distance from a supermarket as well as socioeconomic factors, such as household income and access to transportation. Food deserts in rural areas are often 10 or more miles from a supermarket whereas distances for urban areas are much shorter (e.g., 1/4 to 1 mile).

Opponents to expanding health care access often argue that doing so bails out individuals whose health outcomes are a result of poor lifestyle choices, such as an unhealthy diet or lack of physical activity. Although unhealthy lifestyle choices have been shown to impact a wide variety of disease states and conditions (including CVD), this argument assumes that all individuals have equal access to healthy options and the capacity (i.e., income) to select them. (more…)

Addressing the cardiovascular drug shortage crisis: a call to action

A 62-year old man with a history of heart failure presents to your intensive care unit with shortness of breath consistent with acute pulmonary edema. You plan to initiate a nitroglycerin infusion, only to find out that the hospital has prioritized the few bottles it has left for patients being admitted to the emergency room with chest pain. You consider a sodium nitroprusside infusion, but recognize that its adverse effect profile makes it a less ideal choice in this patient. You also order a dose of intravenous furosemide but are told the institution has exhausted its supply, requiring that bumetanide be used as an alternative. Because all of the hospitals in your area have also had to switch to bumetanide, it too is available in limited quantities. The providers on your team are also unfamiliar with its dosing and administration, placing the patient at an increased risk for adverse events due to medication errors.

Although the above scenario probably seems like a clinician’s worst nightmare, it has become an all too familiar reality given the ongoing drug shortage crisis in the United States (US). Because an estimated 1 out of every 10 drug shortages affects patients with cardiovascular disease (CVD), several colleagues and I recently examined the issue as part of a report for the American Heart Journal (AHJ) (1). In addition to exploring the causes and consequences of cardiovascular drug shortages, we also developed recommendations for professionals involved in the care of patients with CVD. Highlights from our findings are included below, and a fully accessible version of our report can be downloaded here. (more…)

Healthy vending: sending a consistent message to patients

One out of every three adults in the US is obese, and obesity-related disorders such as cardiovascular disease and type 2 diabetes are at an all-time high (1) (See Figure). Similar trends have also been observed in the rates of childhood and adolescent obesity. Among the major contributors to this growing epidemic is a diet increasingly comprised of high-calorie foods and sugar-sweetened beverages (2).

Consuming a healthy diet is one of the cornerstones of disease prevention, and the evidence suggests it works. Along with other therapeutic lifestyle changes such as increased physical activity and smoking cessation, eating a healthy diet can dramatically reduce the risk of heart attack and stroke (3). According to some experts, if patients received all of the healthy lifestyle interventions for which they were eligible, the rates of heart attack and stroke would drop by 60% and 30%, respectively (4). (more…)

Gun violence and mental illness: important but separate conversations

When asked this morning about President Obama’s plans to issue an executive order on gun violence, Republican frontrunner Donald Trump told Face the Nation host John Dickerson that there were already plenty of things that could be done to address the issue, and that we should focus on what he called the “tremendous mental health problem” in the US.

Trump is right—we do have a mental health crisis in the US. However, where he and several other presidential hopefuls get it wrong is that they inappropriately link it to gun violence. Doing so also presents a conundrum for mental health experts, who could otherwise capitalize on the spotlight that politicians have placed on mental health reform but must at the same time admit that it is unlikely to deter gun violence (1). (more…)