Mark S. Senak's Blog, page 2

What They Said – Reviewing the First 6-Months of FDA Communications

Every six months, we do a look-back to see what has changed in the way that FDA is communicating. One might not think there is much difference over time, but there is. For example, the air has pretty much gone out of the COVID balloon. And there is more to tell.

How many? First of all, consider volume. The number of press releases issued by FDA during the first six months of the year declined to 101 from the 125 issued by June 30 of last year, the lowest number at mid-year since 2017. In 2018, FDA issued a much larger number of releases – trend that continued through 2022, all years with much larger numbers than were seen in 2017.

The increase can be attributable to two factors. First, the upward tick in releases beginning in 2017 that climbed steeply in 2018 and following slightly the following year matches the tenure of Dr. Gottlieb as FDA Commissioner. During his time at the post, the Commissioner’s office turned the relatively rare practice of issuing statements from the commissioner to a very common one. The second spike occurred in 2020, coinciding with the COVID-19 pandemic. In 2022, the agency issued 27 releases that involved the subject of COVID, 18 of which were during the first half of the year. In 2023, there were just 4.

One factor in the decrease is of course the near-absence of COVID-related news from the agency. But one cannot talk about volume without talking about the different way that FDA is putting out news – specifically the “FDA Roundup“. Prior to 2022, FDA posted news that did not quite meet the press release threshold through a mechanism called “FDA in Brief” which were halted in 2022 and seemingly replaced by the “FDA Roundup” which is housed on the press release page, but which contains a hodgepodge of news items covering actions by the agency during the past few days such as workshops being held or articles that have been published. While the FDA in Brief documents covered only one topic, the FDA Roundup can cover several and includes an update on COVID-related activities, meaning that while the overall volume of releases is down, the overall volume of information may, in fact, be up.

What did they talk about? Looking to press releases by category, there was

So far this year, the agency has had releases in the following categories with a comparison the first six months of last year. There were fewer releases this year, mostly due to a drop in the General Announcement category the bulk of which are the Daily Roundups. There was an increase in the number of approval related announcements (though it should be noted that in the case of Tobacco, the releases were largely in regard to the denial of approval). In 2023 so far, there have also been an increase in Legal (Warnings, e.g.) and Rule (guidance docs, proposed rules). Also of note, while there were 6 alerts in the first half of 2022, there have been none in 2023.

Did they speak Spanish? There are two large Spanish-language television networks operating in the United States, as well as weekly, semi-weekly and daily publications. Over the years of these look-backs, one thing that has stuck out about the press releases is that some of them are translated into Spanish, while many are not. Yet there seemed no obvious way to discern which would be bilingual and which would not. In the first half of 2023, there were 35 releases that were in both Spanish and English – about one-third of the releases overall. In the first half of 2022, there were 44 bilingual releases – also about one-third. But in 2020, there were only 34 bilingual releases out of the total of 154, or about one-fifth. (The Roundups are not bilingual.) It would appear that there may be an indication that FDA is upping the effort here to reach this important audience, though there is still a way to go. And the increase in profile of Spanish releases would also be higher when there are fewer press releases if the number of bilingual communications remained the same.

Overall, there have been shifts in the way the agency is communicating. We’ll be back at year end to see how we netted out.

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It Finally Happened – FDA’s OPDP Issues First Letter of 2023

For those who are regular followers of what FDA’s Office of Prescription Drug Promotion (OPDP) is up to, there was a surprise this week when the office posted the first regulatory action letter – in this case an Untitled Letter (a/k/a Notice of Violation (NOV) Letter) in over a year. The particulars of the letter are interesting, but first a quick review of recent enforcement from OPDP.

Enforcement Track Record – Looking all the way back to 1998, FDA issued a peak of 156 Untitled or Warning Letters in a single year (the prior year it had issued 139). That is the record high for a single year since that time and means that they were coming out a rate of over 12 a month on average. But the numbers began to dwindle and 2013 was the last time the office even issued 12 letters within a year (it did 23 that year). The numbers plummet in 2014 until the record low last year of only 4 letters. The last letter issued came just over a year ago in June, 2022.

Since then, crickets…..until this week.

The Newly Issued Letter – And now to the letter itself. True to form of late, this letter went to a company that is not a household name. It was the second letter for this company, the first having been issued in August, 2020 for a TV advertisement. The latest letter was issued for a website that promoted a treatment for hypercortisolemia in patients with Cushings Disease. The label for the medicine includes a boxed warning regarding potential issues related to complications for the liver (toxicity) and heart (QT prolongation).

OPDP took issue first with the description of efficacy which the agency said picked data points and reported efficacy of studies that, while accurate at that point in studies, did not reflect ultimate data points realized at the end of the final study. Further, the agency said, the product label reflected that a large number of patients discontinued treatment prematurely for multiple reasons and the omission of this information would impact the reader to assess efficacy.

On the risk side, the agency said the copy on the website that referred to monitoring and side effects failed to specifically outline the serious risks enumerated in the boxed warning, referring to them generally as serious side effects (rather than specifically calling out the boxed warning elements) and stating that testing will help a doctor avoid side effects. The agency felt that the lack of specificity combined with the implication that tests could help avoid adverse events minimized the risk realities given the seriousness of the potential adverse events and their frequency as outlined in the label. The agency acknowledged that full risk information was presented on the webpage, but felt that did not mitigate the overall characterization that minimized risk.

The ultimate lesson point in this action letter by OPDP is that when it comes to characterizing either efficacy or safety data, being as literal as possible in reflecting the label is important, particularly on the risk side when a product has a boxed warning.

A Note About Boxed Warnings – One might ask whether products with boxed warnings are more likely to face the possibility of an OPDP action letter. Going back and looking through 2020 at the products involved in letters, there have been a total of 17 letters (involving 19 different communications vehicles). Of those 17 letters issued, 8 had boxed warnings. Of those with 8 with boxed warnings, 5 of them were Warning Letters, as opposed to Untitled Letters. Of those without boxed warnings (9 in number), only 2 had Warning Letters. Not a huge pool from which to pull, but indicative nonetheless.

Back to Enforcement – At nearly the same time OPDP launched the “Bad Ad” program (2010) which is designed to deputize healthcare professionals and others to spotting and reporting potentially non-compliant communications, enforcement began to diminish. The agency holds trainings and gives continuing education credits. It forces the question why the agency would invest in such a program and then have fewer results to show for it? There are no apparent answers. It may be that the agency has focused resources on areas that present the highest risk and impact, and that this is not one of those areas.

Photo by Goh Rhy Yan at Unsplash

FDA Announces New Study on Endorsements and DTC Television Ads

In today’s Federal Register, the agency has announced that the Office of Prescription Drug Promotion (OPDP) is adding a new study effort to its research portfolio. The category of that body of research that is currently underway includes a range of topics, including an assessment of terms and phrases commonly used in prescription drug promotion, studying the comprehension and understanding of multiple indications used in consumer television advertisements, and endorser status and explicitness of payment in Direct-to-Consumer promotion, among others.

In relation to the the last, today’s study announcement is also focused on the role of endorsements – “Endorser Status and Actual Use in Direct-to-Consumer Television Ads”. The notice published by FDA states that the aim of this effort is to complement the endorser status noted above, which apparently has been completed. That study had looked at endorser types in print or internet use to see how disclosure of payment status might impact audience reactions. The new research effort will look at actual-use disclosures in the medium of television advertising. The agency notes that prior research had indicated that the most influential endorsements to lead to purchase intentions were by physicians or pharmacists, followed by consumer endorsements and in last place, celebrity endorsements.

The agency notes that when healthcare providers are used in an endorsement, there should be a disclosure of compensation and that industry principles also recommend that there be disclosure when an actor is being used to portray a healthcare provider, though industry standards do not mentions such disclosure when a consumer/patient is represented by an actor. With the new research, FDA intends to examine the influence of patient/physician endorsements as well as ads where there is a utilizer of the product or an actor to assess attitudes and perceptions of the audience with respect to risk/benefit and behavioral intentions.

Why is this noteworthy?

Two things come to mind. First, direction of OPDP research may sometimes shed light on a developing area of interest in relation to enforcement. In other words, the data that they reap in these studies might inform a principle or perspective with respect to the use of endorsers that could have an influence on what they are looking at with respect to taking enforcement action. That seems a bit of a stretch in this regard, particularly in light of the fact that visible enforcement by OPDP has been close to non-existent. No enforcement letters have been issued during this calendar year, and in fact, the last action letter sent by OPDP was 10 months ago in June, 2022. This seems mostly like an academic exercise rather than anything with substantive impact – still, those who are utilizing endorsements in promotional communications should pay attention to both of these related studies for insights.

Second, it also tells us that even though the tide in communications on both the part of patients and promoters has shifted dramatically to the digital realm – often viewed on mobile devices – FDA’s attention remains focused on yesteryear and DTC advertising on broadcast television.

Presumably the first endorsement related study will be published soon. Keep an eye peeled for insights.

Photo by Ajeet Mestry at Unsplash

Thumbs Up, Thumbs Down – Minimizing Votes in AdComms

FDA Commissioner Califf has voiced a desire to limit voting in Advisory Committee Meetings

Recently there have been a spate of reports carried in trade media that Commissioner Califf would prefer to limit the voting mechanism customarily included as a key part of FDA Advisory Committee meetings. Traditionally, committee votes can be taken on a range of topics during the course of the meeting. These votes are usually interspersed with questions that the agency poses to the committee for the purpose of eliciting discussion about specific aspects in relation to the approval of a new drug application. Customarily this culminates in the ultimate question whether the committee believes that the benefit/risk ratio is such that approval is warranted. Now the Commissioner appears to be suggesting that the focus be put on discussion with less, if any, inclusion of what he refers to in one report as a “gladiator” vote of approval.

The notion to limit voting seems a bit contrary to the character of the current environment – one which would seem to beg for more transparency rather than less. In November 2020 FDA held a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee to consider a new drug application for an investigational treatment – aducanumab – for Alzheimer’s. The standing voting members of the committee (7) were joined by 4 additional temporary voting members. FDA posed a total of 8 questions for the committee’s input into the agency’s decision, half of which were discussion questions and half of which were voting questions. It went something like this:

The first question posed to the committee in that meeting centered on one of the clinical studies that had been submitted in the application and asked whether it provided strong evidence of efficacy and the committee overwhelming voted that it did not (1 Yes, 8 No, 2 Uncertain). The second voting question focused on a different study, asking the same point regarding efficacy and again the vote was overwhelmingly negative (0 Yes, 7 No, 4 Uncertain).Asked whether there was strong evidence of a pharmacodynamic effect related to Alzheimer’s pathophysiology, the outcome was a little more balanced, but still not an endorsement (5 Yes, 0 No, 6 Uncertain). Returning to the study voted on in the first voting question, the agency then asked whether it was reasonable to consider the study as evidence of efficacy in the treatment of Alzheimer’s and the vote was once again overwhelming (0 Yes, 10 No, 1 Uncertain). Several months later, FDA approved the NDA under accelerated approval provisions, a possibility that was not something discussed at the meeting.

The results were disastrous from nearly any way you look at it. FDA pointedly ignored the overwhelming sentiment of the panel, resulting in the unprecedented resignation of 3 of the advisory committee members. CMS issued a national coverage decision to limit coverage for the drug by implementing a policy that it would only cover monoclonal antibodies approved under accelerated approval for Alzheimer’s for those patients who had been in the clinical trials, pretty much guaranteeing that uptake would be limited. Confidence in the approval process was shaken and FDA’s reputation took a blow. The outcome fostered confusion among patients and physicians. And among the many negative side effects of the decision, there was a Congressional investigation highly critical of FDA’s lack of transparency in the process, among other things.

The Aduhelm case study is an example of why voting is in fact essential.

In referring to the voting tradition in the meetings as reported in trade media, the Commissioner stated words to the effect that the advisory committees exist to give the FDA advice and that approval decisions should be left up to full time civil servants. In the same article he’s quoted as saying that these meetings are like a democracy – where there is not always agreement – and therefore sometimes messy. But while the committees are there to provide FDA advice – and ultimately the decision does rest with FDA, AdComms also serve another very important purpose.

With votes, we get not only the qualitative insight yielded to us by the nature of the discussion, but a quantitative understanding as well. It makes the outcome concrete. We are left with a good perspective on whether the committee is wholeheartedly enthusiastic, fence-sitting, or in the case of aducanumab, very much against approval. We don’t have to read the tea leaves. Votes are a fundamental component of transparency to those of us on the outside and the considerations that go into an approval decision are known and understood by everyone. Part of understanding is provided by the discussion, but a part is also the mechanism of a vote. And to the Commissioner’s point regarding “messy democracy” – in point of fact, voting is a fundamental component of the democracy to which he refers.

Commissioner Califf’s thinking on this has been through various reported conversations and has not been embodied in a speech. The topic merits wider consideration though and a more thoughtful and contextual discussion. Hopefully that will happen.

Can we at least vote on it?

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Big Decisions – Reviewing FDA Advisory Committee Outcomes Since 2020

In January we took a look at FDA Advisory Committees (AdComms) – FDA AdComms – When the Going Gets Tough – noting, among other things that there had not only been fewer meetings but also that it appeared that the outcomes were increasingly negative.

Just to recap, for the entire year of 2022 there were only 14 meetings held to consider whether new medicines should be recommended for approval, a slight increase over the 10 the year before, but considerably lower fewer than 2018 and 2019 when there were 29 and 22 meetings held, respectively. And as can be seen by the increase in red bars (negative outcomes) and the decrease in positive outcomes (green bars), the outcomes have skewed increasingly negative, with 2022 being a particularly negative year. Note these numbers cover meetings about drug applications only, not including vaccines or cellular therapies.

By contrast, already in 2023 there have been eight AdComm meetings scheduled by FDA for the purpose of considering a new medical treatment, three of which have occurred and all resulting in votes in favor of the sponsor, so perhaps 2023 is heading to less negative territory. During the balance of this month and into next, there are five more meetings scheduled, so we shall have to see.

That tells the collective story, but how do each of the committees fare?

The committee with the most AdComm meetings was also one of the committees with the highest number of negative outcomes – the Oncologic Drugs Advisory Committee. The committee met a dozen times during 2022 and only voted in favor of recommending approval four times. Two committees – the Endocrinologic and Metabolic Drugs Advisory Committee and the Antimicrobial Drugs Advisory Committee were among those that met the fewest times – once and three times, respectively, but both had purely positive outcomes. In fact, bottom line, there were nine different committees that had meetings to consider new drug approvals last year, only four of them voted positively 50% or more of the time, with five of them voting negatively more often.

There are a lot of variables that factor in. Drugs for cancer face a whole different set of criteria for assessing safety and efficacy than do other therapeutic categories. That said, beginning in 2020 meetings began skewing to more negative outcomes and 2022 was the first year where the number of negative outcomes outweighed the number of positive outcomes. As noted earlier, this coincides with the transition to virtual meetings over in-person ones.

But the nature of AdComms may be in flux calling into some question the role and influence of voting. Recently, Commissioner Califf was quoted in a few articles this month reporting on a moderated discussion in which he participated at the Biopharma Congress meeting held in Washington, D.C. in mid-February. The coverage in part focused on his thinking that advisory committees need to be less aimed at actual votes rather than on having a full discussion of the issues. Apparently these comments did not come in the form of a speech which would be listed on the FDA’s website which might provide some context – because on their own, they are rather confusing. More thinking about this in an upcoming posting, but it signals perhaps that the nature of AdComms may begin to skew less to circumstances where there are voting questions posed to the committee and that there may emerge a more consistent use of “discussion” points instead. If so, that will certainly complicate future big picture analyses, forcing the discussion to be more qualitatively than quantitatively focused.

Emerging from Emergency – Two COVID-Related Developments This Week

Two announcements occurred this week, both of note and connected only by the fact that they are emblematic of the slow metamorphosis from a COVID emergency world to a post-COVID emergency one.

Emergency Ends – First, the Biden Administration announced that it would be allowing the Public Health Emergency (PHE) declaration to lapse this coming May. In a separate (and pointless) development, the U.S. House of Representatives voted to end the declaration – theater-legislation given that the initiative would never be passed into law and the policy decision was already made. The PHE, initiated during the prior Administration and extended repeatedly by the current Administration, put into place a number of policy initiatives in relation to the COVID-19 response, most significantly initiatives that enhanced the ability freer access for people to get vaccines, medicines and testing. With the end of the PHE declaration, access for individuals will shift away from government support and rely on a person’s insured status (either public or private) and any state policies in effect.

Impact on EUAs? One aspect largely missed in the media reporting on the PHE conclusion is in regard to whether or not the action has an impact on the Emergency Use Authorization (EUA) status conferred by FDA on a number of vaccines, diagnostic tests, and medicines during the COVID emergency. However, the PHE that will end on May 11 is distinct from the separate from the mechanism that allows FDA to issue EUAs for medical products. Therefore the status of those medical products that have EUAs will not be affected by the ending of the PHE, declared under the auspices of the Public Health Service Act. The emergency declaration that confers the ability of FDA to issue EUAs is a separate regulatory mechanism and is part of the Federal Food and Drug Cosmetic Act. FDA has stated in an updated FAQ on the topic that any change that would impact EUAs would first be published in the Federal Register with ample time provided for transition of products from EUA status.

Face-to-Face Meetings – On a separate note, it was reported this week that FDA will be engineering an eventual return to in-person meetings with industry. FDA has provided an update on the website regarding Face-to-Face (FTF) meetings with staff transitioning in 2023 to return, at least part of the time, to the FDA campus.

Impact on AdComms? While it is almost impossible to think of that absolutely HUGE campus empty all this time, the return naturally raises the important question as to how this change will impact industry, with specific attention to FDA Advisory Committee meetings. In a prior post, it was noted (without making a causative connection) that since meetings went virtual, they have also gone more negative, with a higher rate of “no votes” than in prior years. In the communication regarding the transition, FDA has stated that they will be re-fitting conference rooms with some fancy new equipment – face/conversation tracking cameras and boom forming microphones for example – and the agency will have in-person participation likely limited to those with speaking roles, while others will be relegated to a virtual presence. Hence, a hybrid meeting. Because the number of rooms will be limited, but growing over time, these types of meetings will seemingly start out few and expand as re-fitted facilities come on line. The agency is targeting smaller industry meetings for this effort. Sadly, no mention yet of FTF AdComms.

It would appear that we are emerging, in some respects, glacially from the COVID era. As noted in the previous posting, FDA is talking less about the pandemic than before. And while it is good to have this in the rear view mirror, it is worth noting that daily mortality is still high, people are still hospitalized at a high rate, and many people are still getting sick with it for the first time. We are moving on, but the pandemic is still very much with us.

Photo by CDC on Unsplash

What They Said – Looking Back at FDA Press Releases During 2022

Each year Eye on FDA provides a look-back to see what the agency was talking about and what has changed over time. This year is a telling one and FDA may be changing the nature of the way they are communicating with the public. Moreover, this year is marked by the fact that the agency appeared to have less to say than in most recent years – perhaps taking a breather after the frenzy of the COVID-19 pandemic years.

Overall Fewer Press Releases – During 2022 the agency issued fewer press releases than in most previous years – 237 down from 285 the previous year and the fewest releases since 2017. There may be several factors at play. Not only was there less activity in relation to the COVID emergency, but we have had a change in leadership at FDA, which can have a big impact on how the agency communications. For example, when Dr. Gottlieb became FDA Commissioner he embraced the issuance of “Statements from the Commissioner” as a vehicle for talking about a vast array of topics, causing a huge spike in the number of releases from the agency. Prior to that time, such statements were very rare. With Dr. Califf at the helm, those statements have been used with far less frequency, issuing only a few this year. And in addition, there were far fewer new drug approvals in 2022, particularly new molecular entities, which means that there was less to talk about in that regard. The Air is Gone from the COVID Balloon – Needless to say, as the COVID-19 pandemic picked up pace, so did the agency’s involvement in approving new vaccines, new treatments and in addressing the thirst for reliable public health information. But the volume of COVID- related news has fallen off dramatically as has the agency’s activities. In 2020 there were 277 press releases related to COVID, with 144 in 2021, falling precipitously to only 27 in 2022. The chart below demonstrates the diminishing role on a month-by-month basis of COVID related releases (represented by the red area). FDA Began a New Method for Dispersing News – In prior years, the agency used to post news items that were not quite worthy of press release status in a vehicle called “FDA in Brief” that were posted in a place on the FDA website apart from traditional press releases. Beginning in 2022, however, FDA began to issue “FDA Roundups” which were included as part of the lineup of press releases, and “FDA in Brief” postings came to a halt. The new FDA Roundups contain a hodgepodge of news items rolled up into a single communication, topics which are not likely on their own worthy of a press release and which include mentions of COVID-related developments. They are generally issued usually twice a week, every third or fourth day, but not always. Unlike many of the agency releases, they are not translated into Spanish. This mechanism signals a whole new way for the agency to communicate its activities. What They Talked About – Finally, when they were talking, what were they talking about. As already noted, there were fewer approvals and less COVID-related material. There was a higher number of releases that were available in Spanish as well as English – and since there were fewer releases, that means that a higher proportion of releases were also in Spanish over years past.

While the number of press releases did diminish this year, given the added information going out in the regular roundups, the actual volume of information may increase. As we look forward to 2023, it may be important to note that since the month started 24 days ago, FDA has issued only 3 press releases in January, with the bulk of information being sent out via the Roundups.

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When the Going Gets Tough – FDA AdComms in 2022

Through its Human Drugs Advisory Committee process FDA has a vast array of outside experts to consult on matters related to product approval as well as questions about policy or safety issues concerning approved products. The mechanism provides an open and transparent process whereby people can see and hear the deliberations and have input during open public comment as well as through a docket established for that purpose.

But for those who have spent years watching – one thing has become clear. FDA Advisory Committees (AdComms) ain’t what they used to be.

First of all, they are all still virtual. At the beginning of the pandemic, FDA moved to staging virtual meetings. For anyone who had to suffer the onerous security ritual at FDA’s campus where the meetings were generally held that may be good news. In-person FDA AdComms were not really fun. The parking lot was light years from the entrance, the security screening was slow and laborious and once you were in, your eating options were quite limited. The switch to virtual meetings has meant that you can now watch and participate from the comfort of your own home – where presumably you can get whatever you want to eat. Ultimately, the virtual meetings certainly get the job done in terms of the exchange of information – even if you do have to put up with a lot of people needing to be reminded to unmute. But certainly the meetings have lost the personal touch lost in all virtual re-setting. You could see who showed up and who talked to who. I can recall a sitting U.S. Senator walking into a meeting to confer once. And there were many open public comment periods that were quite moving as a result of patient presentations in a way that they might not be in a virtual setting. The networking that used to occur – the informal interchanges – those are not happening. So that is one – albeit small – way in which AdComms have changed. But there are others.

Second, and perhaps more important, there have been fewer of them. In 2012 there were 35 meetings held by FDA for the purpose of considering new drug approval which is almost 3 meetings a month. By contrast in 2021 there were only 10 (see blue bars below in the chart tracking meetings from 2017 – 2022).

Yet in the midst of that range, the number of new molecular entities approved by FDA actually increased. Looking at the second chart below, one can see that the number of AdComms since 2018 peaked in the same year FDA approved a record number of new molecular entities (NMEs). But if you look at more recent history, you will see that during years of robust approvals for NMEs in 2020 and 2021, the number of AdComms went down considerably. That means that as FDA was approving more drugs of first impression it was consulting with outside experts through the transparent process of Advisory Committee meetings with less frequency.

As has been speculated here in the past, the drop-off may be a result – at least in part – of the rise of new pathways for drug approval such as Breakthrough Therapy Designation which promise enhanced access to FDA decision-makers, thereby perhaps diminishing the need for outside consultation.

During 2022, the number of AdComms held to consider new products rose a bit over the previous year to 19 scheduled meetings. However, with 4 of them cancelled, there were only 15 applications considered this year through the AdComm process. Pre-pandemic numbers were consistently higher. But conversely, in 2022 the number of NMEs plummeted.

Third, AdComms aren’t as approving as they used to be. In terms of votes for recommendations of approval for new drugs, the track record was a little brutal this year. Of the 15 applications for new drug approvals in 2022 that went to AdComm consideration, the committees gave a thumbs up to only 4 (the green bars) – and in one of those FDA’s decision went against the approval recommendation of the committee and the sponsor received a Complete Response Letter. Moreover, of the 4 approval recommendations, none of them were unanimous votes in favor of the application. On the flip side – there were 11 votes on applications that failed to get a recommendation for approval (the red bars) and one of them was unanimous. In addition to the more negative tone as expressed by fewer approval recommendations, during 2022 there was an increase in meetings that were either cancelled or postponed.

So in sum, over the past few years, AdComms have been consulted less frequently while more NMEs were being approved. And when they were consulted, the outcome has been increasingly negative. Does the COVID-19 pandemic figure in here? It certainly seems that there is a difference between pre-and post- COVID patterns. Perhaps the virtual means for these meetings has an impact beyond the obvious in the deliberation. Or perhaps it is a coincidence. For those having an AdComm in 2023, we will watch and see what happens.

Tick Tock re Tik Tok and FDA’s OPDP

Tik Tok was first released in 2016. While slow out of the starting gate with emergent media opportunities, in 2022, pharma is embracing the platform in both unbranded and branded efforts. While historically, a lot of Tik Tok use has been comprised of individuals releasing videos of them showing off dance moves and physique, the time for embracing the platform by institutional users appears has arrived. This is a familiar pattern, echoing back to the time when bloggers, Facebook and Twitter were dominated by people talking about what they had for lunch, who they were dating and where they were standing. Then commercial interests moved in changing the complexion and makeup of those platforms entirely, with pharma taking up the rear. The emergence of pharma on TikTok signals another facet in the evolution of healthcare communications and a similar pattern.

But while FDA’s Office of Prescription Drug Promotion (OPDP), the office responsible for a FDA’s regulatory approach to promotional speech by the pharmaceutical industry, has recently announced research that is aimed at uncovering more about the role and impact of influence of endorsers, that research is covering more mainstream channels , namely television. Earlier research, the agency says, shows that different types of endorsers have different levels of influence, with physicians coming in highest and celebrities coming in lowest. In the newly announced research, the agency will compare reactions among different subsets of viewers by age and education level. What that research will not tell us is, with its extremely high level of viewership, what might the impact of endorsers be on TikTok?

FDA’s OPDP began considering an approach to regulating social media long before Tik Tok came into being. The agency has always maintained that the principles underlying its approach to addressing promotional speech was somewhat platform agnostic – that a video that plays as a commercial on broadcast television is guided by the same principles as those on YouTube. Communicators and marketers would love black and white answers about concrete platforms. But OPDP speaks not in black and white, but gray. And they believe that the principles laid out to date cover pretty much any communications platform.

But in fact, that is not the case as evidenced by the fact that the agency has different approaches for print than broadcast, indicating the medium does, in fact, matter. And FDA made tacit acknowledgement of the fact when it held a public Part 15 meeting in April 2009 to put forth a framework for the discussion of regulating social and digital media, with the aim of developing a guidance related to the unique challenges offered up by new media shortly thereafter. That did not happen and in fact, it was many years before any draft guidance documents emerged and then there were principally two of them that addressed some of what was discussed in the 2009 framework – on Character Space Limitation and on Correcting Third Party Misinformation.

In fact, the medium does matter. In general, social and digital media have begged new and emergent questions related to regulatory oversight than exist within the confines of traditional print and broadcast. For example, the fact that the very basis of social media is sharing content and providing comment on it make it different in terms of impact and perception. More specifically with regard to Tik Tok presenting a myriad of videos varying greatly in subject matter, quality and taste, it is not an unusual for a user to scroll through videos quickly. It is a process that can often result in partial viewing. Many users get just the intro past the viewer before – whoosh – they are gone. So if on a branded Tik Tok risk information is at the end of the vid, how many people will never see it? Once you get the benefit – why stick around for the risk. What is the impact of that? Does FDA know? Should they? How does the medium impact the goal of fair balance, a key principle for FDA’s OPDP.

Another factor in play is that TikTok is content is most likely delivered to individuals, particularly younger people, on mobile devices. Small screens. So what I’m viewing in the way of benefits – and the impact – may be very different from the presentation of voluminous risk information.

Tik Tok aside, the issue of risk presentation somewhat related to the long-outstanding issue of optimizing websites for mobile, about which FDA has said nothing. Yet for many, mobile is the primary access means for Internet use – and therefore health information-seeking behavior. That means the use of links and in particular, their use in optimizing a web site is taking on increasing relevance in relation to mobile sites or video. And yet use of links has never been addressed fully addressed by the agency, even though it was one of the five principle questions posed by the agency in the 2009 public meeting – the only meeting held on the topic of digital and social approaches. FDA spends a good deal of effort in research aimed at how different communications mechanisms impact perception of risk and benefit, where the research is lacking is telling us whether or not the fact there are varied perceptions of risk and benefit actually matters. Given that there is a learned intermediary – a prescriber – between the patient and the product, what is the real issue at hand when communications about the product may result in varied understandings of risk?

As noted in a recent posting, FDA research has been largely focused on traditional media platforms. But the eyeballs have moved on, it is perhaps time OPDP does as well. OPDP has not produced any draft guidance documents in recent months that are relevant to these issues nor has there been much available in the way of enforcement (only four letters issued so far in 2022) to illuminate the many dark areas. The problem is, it is within those areas in which increasing numbers of us reside and consume our information.

To that end, FDA should consider:

Holding another public information gathering meeting on Social and Digital media such as the one held in 2009 to gain further insights into patterns of use and gain a re-focus on the regulatory agenda that results, particularly given the migration of audiences and emergence of new platforms;Directing more research to discover the important nuances thereto, such as how the ability to scroll before the end of a branded video (where risk information might be) impact perceptions of different types of consumers (FDA is conducting research now into how adolescents perceive risk and benefit) and whether or not impacts on those perception actually presents any greater risk; Direct attention to the development of additional draft guidance in the 2023 guidance agenda for CDER – it is noticeable that there were no Advertising/Promotional guidance potential guidance documents in the 2022 agenda. Along with the lack of enforcement, this leaves a big gap.

That is a start. We are a long way from knowing how Tik Tok influences health behaviors. But one thing is for sure. Studying DTC on broadcast television isn’t going to get us there and an approach to regulating promotional speech in social media is increasingly not platform agnostic. Just wait till be get to the metaverse. If OPDP is going to stay relevant to its underlying principles and purpose, the agenda needs to move more quickly. Tick. Tock…..

Photo by Solen Feyissa on Unsplash

OPDP Outlines New Research

FDA published notice recently that the Office of Prescription Drug Promotion (OPDP) was proposing some new research related to the promotion of medicines by pharmaceutical companies. The research was new (kind of) but the direction was more of the same old focus – direct-to-consumer advertising (DTC).

First, just a note on why the research is of importance at all. OPDP engages in a fair amount of formal study related to various aspects of its mission to protect public health by ensuring that prescription drug promotion is truthful, balanced, and accurately communicated. To that end OPDP employs a broad range of methodologies to explore the impact of various aspects of promotional practices and speech to evaluate impact. The resulting outcome is a body of evidence that (1) can influence either the development of new guidance, or (2) the revision of existing guidance or (3) inform patterns and priorities of enforcement by the agency – and that is why we take note.

Research that is currently underway spans a number of topics, including the use of animation in DTC promotion, the impacts of disease awareness and prescription drug promotion on television, the use of superimposed text in DTC promotion, to name a few. A full list can be found here. And here are the latest being added by OPDP:

Endorser Status and Actual Use in Direct-to-Consumer Television Ads – We have all seen ads on television where a person endorses a medicine. Are they effective? Who do we listen to? In fact, OPDP has already conducted one study to determine how different types of endorsers in print or internet settings and the impact of disclosure of payment status influenced audiences. The agency also noted that prior research has shown that different endorsers have different impacts – with expert physicians and pharmacists being the ones most likely to lead to purchase intentions, with consumers falling behind them and celebrities bringing up the rear. The new research will focus specifically on television advertisements to assess the impact of the disclosure of payment in an ad by an endorser. OPDP will examine endorser type (patient, physician) and will look at the impact of actual use disclosures. The agency is going to examine whether there is a difference of perception by age and education level. Perceptions of Prescription Drug Products with Medication Tracking Capabilities – There have been multiple approaches to supporting patient adherence to taking prescribed medications, ranging from pills with ingestible sensors to mobile apps. OPDP states that there is not much known about the perceptions of patient and health care providers that track medication use or work with a software element to track use. Specifically, OPDP is looking to know when a promotional communication conveys the information about ability to track use, the agency is seeking to assess how that fact may impact the perspective of the audience around risk and benefit. Targeted Mechanism of Action Presentations in Prescription Drug Promotion – When a drug promotion contains the term “targeted” OPDP wants to know if that has an effect on a person’s perception of the safety and efficacy of the product. This is based on a 2014 focus group of healthcare professionals in which OPDP even admits, there was a diversity of opinions but where some may have expressed a tendency to view a product more favorably if the term were used. OPDP is now conducting a survey that looks at how physicians and consumers might interpret a number of terms, including “targeted”. Now OPDP will engage in a study to assess the influence of “targeted mechanism of action” language and use of graphics related thereto in promotional communications.

As one can see, OPDP meticulously follows a thread, sometimes over years, to add definition and context to promotional communications, often highly nuanced. However, the agency has been largely entrenched in its research in traditional communications vehicles – DTC in print and broadcast, for example, without embarking more broadly on research that would provide insight into digital communications. Given the 2009 framework for addressing the regulatory issues associated with digital and social communications and the huge migration by consumers to those platforms and the vigorous use of the Internet in health-seeking information, it would make sense for the research to follow suit. That is particularly true given that the 2009 framework has only been partially addressed by the agency. But for now, we wait.