As winter gets into full swing in the Northern Hemisphere, Robert Califf is at the beginning of his appointment as Commissioner of The US Food and Drug Administration (FDA). This will bring with it substantial changes in 2022 (and 2023) not only within the FDA’s internal functioning, but broadly across the pharma and medtech industries.

There is a relatively obscure conjecture in business operations called “Conway’s Law.” It suggests that when organizations construct communication hierarchies, these hierarchies resemble a recursive self-similar arrangement as that of the larger organization itself. In essence, like Russian Nesting Dolls (matruyeshka), each layer down of an organization makes mini organizations that resemble and communicate like the layer above.

The interesting connection here is that when companies change their leadership, this often catalyzes wholesale changes to these structures. This, then, is often impetus to enact brand new changes to how work is done, or reinvigorate changes that may have been latent. This happens with varying degrees of shocking predictability. So, what will Robert Califf’s appointment change at the FDA? And why does it matter? There are two major reasons:

1. Leadership will change the organization.
2. What the FDA does—and finds important—will make the industry fall in line to follow suit.

The Leadership Derivative
If leadership will change an organization, it must be in a certain way. I can express this in the form:

dL/dt > 0

Meaning, simply, that changes in leadership change organizations over time. What we know to be true is that, in my conjectural equation above: Changing leadership with respect to time leads to non-zero outcomes. Or, perhaps more precisely:

0 > dL/dt > 0

Changing leadership with respect to time leads to a non-zero outcome that can be either positive or negative. But in either case, the company won’t stay exactly static.

We often can’t know the outcome unless we look in retrospect after the new leadership experiment has had a chance to run its course. So, whether Robert Califf’s appointment will be a success or otherwise has a lot to do with providence, chance-y situations, and many other things outside of his control (not least of which are lobbyists, budgetary constraints, activists, and so on). But we can focus on element #2 from our list above: Planning for industry’s change in the forecasted direction(s) of the FDA’s changes.

Where the Head Goes, The Body Follows
You may find that this glib quote is worth a look-up. However, Google will tell you that it comes from Ryan Holiday (2014) in the form, “Where the head goes, the body follows. Perception precedes action. Right action follows the right perspective.” Unfortunately for Mr. Holiday, the framework for this quote originated much earlier and from the far divergent discipline of Judo.

In any case, on the chessboard of regulatory approvals, ‘the head’ in the aphorism above refers to the United States’ Regulatory agency, the FDA. ‘The body’ refers to our industry, which endeavors to garner approval for their investigational medicinal therapeutics. When shifts occur within the FDA—and other global agencies as well, including MHRA, EMA, ICH documents, etc.—they reverberate through the industry and catalyze changes in how work is done.

Probably the most voluminous changes in the industry seen in some time due to a regulatory change were those associated with updates in ICH E6 revision 2. Literal years of change went on within the pharma industry to prepare for the second revision of that document and its associated modifications. Changes in the FDA will come in-part from Califf’s interests and directions toward which he finds it important for the agency to go. And where these directions point, so too will the industry follow.

Forward-Looking Themes At FDA
So, what are these likely changes, then? Well, if I deconstruct what I know of Robert Califf and his messaging internally and externally, they begin with data, and end with data.

First, changes to ‘how’ we measure data in the industry.

Then, using data to determine the changes that were made to data handling were, in fact, robust and effective.

Think of it as an FDA internal CAPA to improve data handling, along with necessary Effectiveness Checks.

Past performance is a fairly mediocre predictor of future behavior. But it’s a predictor nonetheless. So, if we look to some of the things that Califf spearheaded in his last run leading the FDA (as its 22nd Commissioner in 2016-2017), we can get a sense of the directionality of the future, within some margin of error. To that end, he had launched IMEDS in 2017, which allowed drug companies to mine patient safety data to identify potential problems with their drugs. IMEDS lists the following benefits on their website:

• Access to large volume of patient data
• Reliability of an established network
• Direct experience and expertise leveraging FDA’s Sentinel Common Data Model and tools
• Accessing and contributing to collective knowledge building around real-world evidence generation

Califf also, in 2016, wrote an article with his colleague NIH Director Francis Collins, wherein he laid out a plan to create a “learning health system that takes full advantage of digital data to help us make informed choices.” So, what I do know of his past performance and interests is that he is deeply interested in the philosophy of transforming how our industry collects and uses data.

He also has been interested in toughening stances on tobacco as well as opioids, including having opioid manufacturers present different types of data showing risk-to-benefit value of their therapies and longer-term safety data. This is part of a rebalanced approach to reviewing opioid drug submissions to look differently at the benefits and risks.

So, while Califf’s plans for modernizing the way Sponsors and the FDA collect and use patient data were largely shelved in 2017 when he left his office, this is the most evidence-based place to go for understanding what he’ll focus on principally when he hits his stride in his renewed position. The FDA is also working internally on the rollout and establishment of its DMAP (Data Modernization Action Plan) and continuation of its TMAP (Technology Modernization Action Plan), which will be guaranteed to have direct and indirect impacts on the industry. So, prepare accordingly. As is always the case: Chance favors the prepared. 

References

• Regan-Udall Foundation of the FDA. (2021). https://reaganudall.org/programs/imeds
• Califf, R. et al. (2016). Transforming Evidence Generation to Support Health and Health Care Decisions. The New England Journal of Medicine, 375. 2395-2400.

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Ben Locwin is a healthcare industry executive, has been appointed to many boards and committees, and frequently works at the moving frontier of the industry, where the future transitions to the present. He has advised investors, developed new therapies and clinical approaches, and has worked to increase public access to healthcare. He has been featured in Forbes, The Wall Street Journal, USA Today, and other top-tier media.