Most cardiologists assume that the way we currently think about things in cardiology has always been part of our DNA. We are strongly evidence-based, and we are skeptical of mechanisms that have no supporting data. We recognize the limitation of small trials, and we understand how missing data creates bias. We know that rigorous clinical trials are the only way to inform our use of drugs.
Has cardiology always been this way? Actually, no.
Forty years ago, thinking in cardiology was dominated by wonderful story-telling, but without much evidence. Trials were small, and many were not well designed or executed. They often focused on things that we thought were important, based on our beliefs about a disease. We knew that shortcuts commonly gave the wrong answer, but we embraced them because we did not know better.
One man made all the difference: Dr. Raymond Lipicky.
Ray led the FDA Division of Cardiac and Renal Drug Products from 1981-2002. During those 21 years, his unique intellect and way of thinking transformed the cardiovascular drug evaluation and approval process. Too slowly, his approach to cardiovascular drugs is now being adopted in other therapeutic areas.
What was special about Ray Lipicky? Each of us would probably answer that question a bit differently, as would hundreds of others whom he influenced. But in essence, it all came down to a single summary statement.
He taught us how to challenge the casual assumptions that kept getting in the way of progress.
Ray didn’t provide us with a formula as to how to think. Instead, he was exceptional at challenging our basic thought processes. If we assumed something was true, Ray wanted to know why. If we assumed that there was one way to do something, Ray might suggest three other ways.
His favorite reply: “Why do you think that?”
Many of us who were on the receiving end of that question were often stunned by it. There would be a long moment of silence, often with our jaws wide open. Ray would notice the lack of a response, and he would chuckle.
Ray had a unique chuckle. It was never condescending or judgmental; it was never intended to create discomfort. Its entire purpose was to help the listener move to a new way of thinking. The chuckle gave us permission to laugh at ourselves. When we heard the chuckle, we knew it was time to start paying attention.
Ray always asked the really tough questions. How do you know that ventricular premature beats are bad? How do you know that clots in the coronary arteries are important? How do you know that positive inotropic agents are good for the heart?
He didn’t ask these questions because he thought we would come up with answers. He asked because he wanted us to wonder whether the assumptions we had in our heads were actually true. And he pushed us to come up with a way to test our theories using logic and empirical evidence.
The four of us interacted with Ray in different ways during his tenure at FDA and beyond. Three of us were employed at FDA at various times. But Ray’s influence was felt throughout the academic cardiology community, and it was felt in every sector that was interested in cardiovascular drug development.
In the 1980s and 1990s, if you wanted to learn how to think about therapeutics, all you needed to do was to attend a public meeting of the FDA’s Cardiac and Renal Drugs Advisory Committee. In those days, the meetings discussed the pros and cons of over a dozen new chemical entities each year. At each meeting, the members of the committee typically sat along a linear table in front of an audience that was packed with hundreds of people. Ray Lipicky was at one end of the table, and Dr. Robert Temple (who had preceded Ray as Division Director) was at the other. When they had a discussion or a disagreement, you could hear some amazing intellectual discourse. For all of us, those debates opened our minds and our hearts.
Dr. Ray Lipicky passed away last week.
For everyone who works in the field of cardiology today, the loss is profound. For those of us who knew him, worked with him, learned from him, and were transformed by him, the world is suddenly left without the person who had made such a difference.
Why do we think that? Even though we can no longer hear Ray say those exact words, we will always remember them — and him.
Robert M. Califf
Robert R. Fenichel
Packer recently consulted for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Daiichi Sankyo, Gilead, Novo Nordisk, Relypsa, Sanofi, Takeda, and ZS Pharma. He chairs the EMPEROR Executive Committee for trials of empagliflozin for the treatment of heart failure. He was previously the co-PI of the PARADIGM-HF trial and serves on the Steering Committee of the PARAGON-HF trial, but has no financial relationship with Novartis.