Dear Mr. President:

First of all, congratulations on your stunning victory. You’ve re-written the playbook on how to get elected president. Your campaign strategy and tactics will be studied by scholars and politicians alike for years to come.

What you are now reading is an “open letter.” It’s addressed to you, but also intended to have a wider readership. We know you’re dealing with a number of pressing matters right now, but we want to make sure that you are aware of an important issue impacting the health of our people, and our nation’s finances.

We work with managers of corporate-sponsored health plans. They are responsible for the design and operations of these plans. Their biggest concern is cost – which is particularly driven by rising prescription drug expenses. We know you are aware of the rising prices of prescription drugs and are determined to try and remedy that. That’s fantastic. But there is more to the problem.

Not Just About the Price
Better pricing will be a big help, but we still have a value problem. As it is for most Americans, high prices aren’t nearly as bitter of a pill to take when there is tremendous value received (like saving the lives of our plan members).

There are three things people want from their prescription drugs: to be safe, to work, and to be affordable. The last of these, affordability, we’ve touched on already and hope you are “on that.” For the other priorities, we rely on the Food and Drug Administration (FDA), whose approval process is intended to assure us that the drugs work and won’t have any undisclosed or unreasonable side effects. While side-effects are a major concern, we would like to focus your attention at this time on the whole “Does it work?” issue.

The FDA uses two words with special meanings to evaluate whether a drug going through its approval process will “work.” Those words are “efficacy” and “effectiveness.” Probably the simplest way to understand what the FDA means by these words is this: “Efficacy” refers to the benefits a drug produces under ideal conditions, that is, under the controlled conditions of a clinical trial. In contrast, the term “effectiveness” refers to the benefits a drug produces under the usual circumstances of health care practice, taking into account patient compliance, dropouts and drug-to-drug interaction, etc.

Setting a Standard
Anymore, Mr. President, it seems like we measure everything – from exit polls to the time it takes a quarterback to release the ball. That may lead one to believe the FDA reviews all clinical trials a drug goes through and then determines a measurement for the efficacy shown, say 85/100 or assigns a grade like A, B or C. But no, that isn’t how it happens at all, Mr. President. In fact, there is no particular level of efficacy required for a new drug to be approved by the FDA.

How can this be? Well, the legal standard for the efficacy a new drug must demonstrate before receiving FDA approval is set forth in Title 21 of the United States Code, which essentially states: the drug merely has to show more than a non-zero level of efficacy under perfect conditions.

This means there is nothing to prevent the FDA from approving substantially ineffective drugs. And the implications of this approach are alarming. It raises the specter that the stamp of “FDA approval” may actually work to harm the health of our plan members and the larger public.

For example, we have Opdivo, the new and heavily advertised lung cancer drug, targeting the desperate hopes of those afflicted, promising “a chance to live longer.” How much of a chance to live how much longer is not stated. All we know for sure is that there is a chance greater than zero that a patient might live at least a day longer. Is that minimum standard acceptable for an FDA-approved drug? This is even more disconcerting when research indicates that 86% of cancer drugs do not lengthen patient lives.

Mr. President, please consider these concerns as you select the next Commissioner of the FDA. One of your candidates was quoted as saying, “We should reform the FDA so there is approving drugs after their sponsors have demonstrated safety—and let people start using them, at their own risk, but not much risk, of safety. Let’s prove efficacy after they’ve been legalized.” Views like that put the burden of determining a drug’s efficacy even more on patients, who, bombarded by advertisements, are the least capable of making these decisions.

Hope on the Horizon?
The good news is that there are serious attempts to try and fill this gap. The most prominent organizations working on this include the American College of Cardiology and the American Heart Association (ACC–AHA), the American Society of Clinical Oncology (ASCO), the Institute for Clinical and Economic Review (ICER), Memorial Sloan Kettering Cancer Center (MSKCC), and the National Comprehensive Cancer Network (NCCN). However, each of these organizations is taking a different approach to determine efficacy and value.

What we need is a comprehensive, evidence-based effort – something the FDA is equipped to do and apply – if only it can get out from under the appallingly loose standards of Title 21. You’ve already called Big Pharma’s bluff on prices. Please complete the job and require meaningful efficacy standards as well. You can make this happen. Even if “C” or “D” quality drugs are being approved, we can use the FDA’s help in letting us differentiate them from the “A” and “B” quality drugs.

Is the best approach to leaving this responsibility up to insurance companies and employers? We are not sure pitting the payers against the manufacturers and their advertising dollars best serves the needs of your constituents or ours. You have the leverage, Mr. President. We’d be happy to help. Just give us a call.

“Greater awareness of the [FDA’s] illusory efficacy standard is badly needed in order to enable physicians, patients, governments, and society at large to make rational choices about the risks they are willing to undertake and the medicines for which they are willing to pay.”


Jonathon J. Darrow
Research Fellow, Harvard Medical School
Postdoctoral Research Fellow, Brigham and Women’s Hospital