Back to Basics with the Jackson 5 – It’s ABC, as easy as 1, 2, 3: OPDP Issues the Most Unsurprising Untitled Letter of the Year

June 9, 2022By Jeffrey N. Wasserstein & Dara Katcher Levy

While the Jackson 5 hit “ABC” predates even these rapidly aging bloggers (first performed on Dick Clark’s American Bandstand in 1970, and we challenge you to name all five members of the Jackson 5, we tap out after Michael, Tito, and Jermaine), its basic wisdom remains unchallenged when it comes to developing promotional materials.  Althera Pharmaceuticals, LLC would have been wise to follow this advice in formulating its professional piece for healthcare professionals for ROSZET (rosuvastatin and ezetimibe) tablets, for oral use (here and here).  ROSZET is indicated to reduce cholesterol in certain groups.  As discussed further below, Althera chose to mess with both the A, B, C’s and the 1, 2, 3’s and got the untitled letter.

Let’s take these in reverse order, as FDA did.

1, 2, 3, Or, Don’t Make Up the Numbers

FDA’s primary complaint about the piece is that Althera included claims of cholesterol reduction ranging from 64% to 72% depending on the dose.  Pretty impressive dose reductions, no?  There’s only one problem:  These numbers “are not the findings of any study of Roszet.  Rather, the analysis used to generate these percentages combines the results of two separate and unrelated studies” from the package insert.  (Untitled Letter at 2).  The two studies were a monotherapy study that included rosuvastatin and a combination study that added ezetimibe to ongoing statin therapy.  Here’s the kicker:  the latter study didn’t even include rosuvastatin as one of the statins under consideration.  FDA did all but write “we shouldn’t have to say this, but don’t make numbers up.”  FDA had similar complaints about other claims.

As seemingly obvious as this is, there is some more generalizable advice when creating promotional materials.  Companies can’t just average information from different studies.  If the studies have different time frames, different patient populations, different dosing regimens and the like, you can’t just combine the numbers and average them.  Care must be taken that the combination of studies is scientifically and statistically valid.  When in doubt, leave it out.  (budding lyricists here.)  And of course, don’t make up the numbers.

A, B, C, Or Size Does Matter

OPDP’s primary concern with the risk presentation is that the prominence and readability do not reasonably compare with the information on the benefits of ROSZET.  Whereas the claims of benefits are presented in conjunction with colorful graphics (much like the plaid shirts our mothers dressed us in when the Jackson 5 were big – check out the threads in these two originals of your bloggers here and here) and with large bolded headlines and lots of white space, the risk information, including contraindications and warnings and precautions were written in small font and paragraph format and relegated to the bottom of the first page.

Context matters not only to the substance of claims and safety information, but to the presentation of such information as well.  It need not be a 1:1 relationship, but it does need to reasonably compare.

Teacher’s Gonna Show You, How to Get an “A,” Or, Let’s Not Forget About 21 C.F.R. §202.1

Promotional pieces like this have us scratching our head.  On the efficacy side, maybe the focus was on the claims being “consistent” with the labeling, forgetting that the claims still needed to be adequately substantiated.[1]  And, on the safety side, maybe the inclusion of extensive “Important Safety Information” led to forgetting that fair balance is not just about quantity, but about comparable prominence and readability to the efficacy information presented.  It’s times like these when we would highly encourage a re-read of 21 C.F.R. §202.1 to level-set on regulatory requirements.

We wish there had been a TV or radio ad so we could work in the do, re, mi part of the chorus and really beat this dead horse, but there isn’t, so we’ll close with this.  Don’t get tripped up on the basics.  Make sure the numbers are scientifically valid and make sure the risk information is presented in a roughly equivalent manner to the claims of efficacy.  In other words, all members of marketing departments and promotional review committees would be well served to remember that:

Reading, writing, arithmetic
Are the branches of the learning tree
But without the roots of love everyday
Your education ain’t complete

[1]              As a reminder, FDA’s 2018 Guidance, Medical Product Communications That Are Consistent With the FDA-Required Labeling Questions and Answers, provided a mechanism for communicating “consistent” claims that are scientifically appropriate and statistically sound (SASS).  While the Guidance recognizes that the SASS standard may be a lesser standard than “substantial evidence,” claims still require scientifically appropriate substantiation.