Mark S. Senak's Blog, page 3

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

Periodically I write a posting to look back at what FDA is talking about to get some perspective. Each individual press release tells us something, but looking back at the aggregate can also provide insights. Not long ago, a retrospective look that compared the ratio and trend of COVID versus non-COVID related news out of FDA suggested that not only was COVID becoming less of a topic for the agency, but also presented the possibility that there was increasing room for other topics. Soon, we may have a new dominating topic in Monkeypox. So let’s take a look:

Volume – Let’s look first at the numbers of releases issued by FDA for the first six months of the year. It is down – mum has been the word. Below is an annual comparison looking back the past few years, compared to where the agency was at mid-year. You can see early in the chart, FDA maintained a very low volume of communications, and at mid-year in 2017 had issued only 52 releases, rising to 166 for the year. This year at 128 mid-year, the agency is at the lowest level since then. You can also see that the numbers rose significantly starting mid-year 2017 through 2019 which coincides with the tenure of FDA Commissioner Gottlieb, reflecting his outgoing communications style. Then the agency began quite commonly issuing Statements from the Commissioner. Prior to that time, such statements were rare. The current downturn in volume could also be attributable in part to the fact that FDA has once again altered somewhat a past communications practice. For many years the agency conveyed news that was not exactly press-release worthy by issuing a separate communication called “FDA in Brief“. This year, the agency stopped issuing news via this mode, and instead began issuing regular releases under Press Releases called “FDA Roundup” that similar bundles news together. One might expect the addition of another regular release from FDA to inflate the volume of releases, but one could also make the case that the bundling of such news created less of a need for individual releases. Content – Next up – what did FDA talk about? In a February blog posting I noted that by January 2022, the proportion of press releases that were issued by the agency regarding COVID was decreasing in proportion, meaning that there was more oxygen available for other topics. The trend is even more stark today and clearly FDA has moved on to talking about other things. So first observation, volume is down, but volume of COVID news (represented in red below) coming out of the agency appears way down. Some COVID-related developments are covered in the newly launched FDA Roundups, but as stated earlier, that tends to group items together that are not quite newsworthy enough for stand alone releases. During the first half of the year, the agency issued 20 COVID-related releases, compared to 93 during the first half of 2021.

Apart from COVID, of the 145 releases issued during the first half of the year, over one-third were the FDA Roundups. Only 20 were about product approvals or label expansions, compared to 46 the year before (the drop in NME approvals was covered here not long ago).

All in all, it would appear that less talk about COVID and with fewer new approvals, the overall output from FDA has gone down with respect to major announcements. One thing that appeared to get a good deal of attention by FDA involved updating the public with regard to developments around the shortage of baby formula experienced in the U.S. this year. We’ll report back after year-end to look at the year and see if there are any changes.

Photo by AbsolutVision on Unsplash

Here We Go Again – Monkeypox Communications Challenges

Source: CDC

In February 2020 I published a blog posting – Emerging Pathogens, Communications – that encapsulated my observations and learnings from my years work in the early years of the HIV/AIDS pandemic in the early 1980s. As we sit, possibly, on the cusp of another large scale medical challenge with monkeypox, it seemed like a good idea to revisit the topic. When there is a new and scary thing we are facing, medically speaking, there are some truisms regarding the communications environment that can inform strategic thinking about how we talk about it.

Facts are low, speculation is high – And nature hates a vacuum and there will be many who are willing to fill the void with misinformation. People want facts, and the fact is, facts are in short supply. Numbers don’t mean a lot – First of all, they change quickly – and are changing very quickly with monkeypox. In addition, there is often a lack of accurate reporting for many reasons. Points of reference will change – What we know, and what we don’t know, will change over time as we get more experience and gain wider understanding. That might seem like a good thing, but in fact, changing stories undermine credibility. Fraud potential is high – There are people who will take advantage of the situation and exploit it for political and/or financial gain. That, too, impacts credibility and can confuse people. Policy is likely to be ham-handed – Policies may be developed quickly and without adequate information and be based on emotion and bias more than facts. This is another factor that strains credibility.

Monkeypox is not COVID, and COVID was not AIDS. They each present distinct challenges and evoke particular fears and concerns. There are big differences between the three. But they are all viruses. And when it comes to communications challenges there are many commonalities.

First and foremost, in the absence of facts, fear can drive actions. And when a pathogen is newly emerging, facts are greatly outnumbered by questions. The degree to which companies, educators, businesses and service providers may want to prepare to deal with those challenges may depend on where they are, who their stakeholders are, and how big or small they are. At this stage though, better to consider the challenges that may lay before you know, before they present themselves.

Source: CDC

Analysis

It may be that monkeypox is contained early if we are lucky. There are reported signs that transmission may be slowing in the U.K. and the trend in the graph above appears to show some deceleration. That said, the numbers have increased quickly on an extremely steep curve. That means there is an increasing amount of virus out there. The virus has mainly spread among men who have sex with men and transmission is being attributed to skin contact. But the higher the numbers go the greater potential there is for more lateral spread. A presumptive pediatric case was reported last week in California. It is also a virus that can move between people and animals.

Containment depends on systems that are able to screen, test, treat, and prevent (both by means of avoiding circumstances that can enhance transmission and by vaccination). To that end, many things are not in our favor. An extremely splintered approach at federal, state and local levels impacts the coordination of a public health response. We have COVID fatigue in the extreme. And in terms of tools, we do not have a means for screening, meaning we do not know who is infected before they exhibit symptoms which may take several days; the testing situation is complicated because there is no quick, at-home testing like there is for COVID and may be best applied when there are lesions. But people may have other symptoms such as headache, chills, muscle aches, swollen lymph nodes and exhaustion. The only FDA-approved drug to treat is approved for smallpox, but no Monkeypox and has been difficult to access. In terms of prevention, while a vaccine has been developed, supply is very short and it, too, has been hard to get.

Additional challenges include the fact that the course of illness runs two to four weeks. If a person must self-isolate for that length of time it is not only difficult, but there may be unintended consequences. With men who have sex with men comprising the overwhelming majority of cases, a diagnosis is the equivalent of coming out. For many gay men that is not a problem. For many others, who may have wives and children, it can be a very large one, facing a situation that may have both personal and professional peril.

At the present time, there are some states which are reporting higher numbers than others. If the numbers do continue to climb, then a larger number of geographies will be impacted and most likely a wider circle of people, raising the chances that large employers, those in specific sectors, may face communications challenges sooner rather than later such as:

Travel and hospitalitySchools and universitiesHospitalsInstitutional settings such as daycare centers, rehab and nursing homes (a case of a daycare workers was reported in Illinois last week)

What to Do

Every business, service or place of public accommodation is different. There is no one-size-fits-all approach to preparation. One must consider the size of the enterprise, the stakeholders and the level of physical contact and interaction with surfaces. That said, there are echos from both AIDS and COVID that shed light into how people may react to the emergence of another communicable condition. A few things to consider:

Review policies and assess what may need to be changed or amended; this is not just COVID return-to-work policies, but discrimination policies as well. Re-think many of the things you have had to communicate about a virus transmitted by air, and re-fashion to think about surfaces. Monkeypox will present distinct challenges. Consider the questions and issues you may face. Can we catch monkeypox using the toilet? Trying on clothes? Do I have to sit next to the gay man? My co-worker says it is eczema, I’m afraid it is Monkeypox. Depending on your business, your clientele, there are different sets of questions that may arise for different settings. Think about what they might be and to what degree you are the one to have to provide the answers. Assess the triggers for potential fear and conflict between employees, customers and users of any service.Communicating in an environment where what we know changes, and what was certain yesterday may be uncertain tomorrow is always a strain on credibility. Therefore consider integrating reminders to that effect in your communications. What we know now is…. Gather reliable resources – the obvious ones such as CDC, FDA, and Departments of Health at the state and local levels, but also consider credible grassroots organizations, particularly ones that may resonate with stakeholders, particularly those dealing with gay-related health issues and key medical societies such as the American Society for Microbiology and others.

Many people think that preparation during such a nascent phase of the outbreak is over-reacting. I hope they are right. But having lived through AIDS and COVID, and seen early numbers quickly spell a different story over a very short period of time, one may be well-served to think it through now.

Speaking of Medicine – Mid-Year OPDP Enforcement Review

There are two means of gaining insight into the agency’s thinking about regulatory issues related to promotional communications by pharmaceutical companies; one is through the issuance of guidance documents, the other is through enforcement.

But when it comes to enforcement things have changed greatly over the years. In 1998, there were 156 letters issued in a single year. By 2002, the number had dropped to 28, reviving somewhat by the end of that decade when it reached 52 in 2010. And since 2014 the Office of Prescription Drug Promotion (OPDP) has broken double digits only 3 times, producing only 6 letters in both 2020 an 2021. So far this year, we are at 4, which is a pretty good clip these days.

While it is difficult to discern trends with such a small number, an examination of recent warning and untitled letters reveals some possible shifts in priorities and emphasis that may be worth noting. That is particularly true since we have a new FDA Commissioner, a new head of the Center for Drug Evaluation and Research (CDER), and a new head of OPDP.

The 4 letters issued this calendar year:

Involved 3 Untitled Letters and 1 Warning Letter – a profile not out of proportion given that about 33 percent of letters issued since 2004 have been Warning Letters. One of the letters came to attention of FDA reviewers through the Bad Ad Program.These 4 letters related to 5 different communications vehicles, 4 of which involved digital forms of communications – 2 were videos, 1 was a web page and 1 was an Instagram posting, one of the rare letters involving a social media platform. If you would look back to 2008, when digital and social media were in ascendancy by pharmaceutical companies, and compared enforcement involving traditional means of communications to those on digital platforms, letters from OPDP more commonly involve traditional means of communications (brochures, DTC print ads, etc) over digital (web pages, social media). While these most recent letters represent a small sampling, the fact that digital is over-indexed here potentially signals a heightened scrutiny involving digital platforms.It should also be noted that one of the videos involved an oral statement made by the CEO of a company which was posted to a third-party site. The characterization of investigative data resulted in a violation related to promotion of an unapproved compound. This perhaps emphasizes the role of media/message training prior to public-facing statement (at all stages of development). The single letter involving a traditional communications platform was a printed information sheet directed to physicians. Violations this year so far were 9 and included risk presentation deficits (3 letters) Superiority Claims and Unsubstantiated Claims (2 each) and Promotion of an Unapproved Drug (1). Some of the triggers included The use of studies in relation to a claim where the studies were unrelated and conducted in different patients for different lengths of time and were limited in design and analytic strategy;Risk information that was presented in small bring, out of balance to the claims presentation as well as another risk presentation that offered risk in a fast-scrolling video that was out of sync with the benefits information;A claim related to efficacy that did not more narrowly define the intended population as reflected in the label

When you view enforcement activity through a broader lens to get more examples to analyze, a few things stand out. Most notably, while promotion of an unapproved drug is a relatively rare violation, comprising only 2 percent of all the letters issued since 2004, it is 13 percent of all letters issued since 2016. Correspondingly, the instances of promotion of an unapproved use has diminished and was last named as a violation in 2019.

Finally, one characteristic of the regulatory action letters issued by FDA’s OPDP over the past several years is that they have principally involved smaller, lesser-known companies. It was very rare to see a company in the top 25 companies cited for violations. But this year and last year we saw Lilly receive two letters, Bausch receive one, and Amgen receive one. It may be an anomaly or it may signal a shift. For any trends to become apparent, there will need to be more enforcement actions. And for that, we must wait.

New Approvals in 2022

We are at mid-year, a good time to check in and see how we are doing on a number of fronts – including where we are with new drug approvals. Over the years, Congress has acted to enhance the ability to bring more new treatments from test tube to medicine chest more quickly. Most notably in 2012 the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law, bring to bear among other things, breakthrough therapy designation. Since that time, there has been a healthy output of new treatments.

But recently in the larger environment, there have been several factors that may have inhibited the flow of the medicine pipeline. The most obvious impact is that of COVID-19 to recruiting and maintaining clinical trials. And then there is the fact that a number of clinical trials were being conducted either in Russian or in Ukraine prior to the outbreak of the war. On top of that, COVID-19, while representing a good deal of medical progress, also represents a tremendous diversion of resources in time, money and effort that might have been otherwise utilized. Finally, COVID also impacted FDA’s ability to manage the regulatory process itself. Advisory committee meetings have been far fewer and observationally speaking, FDA seems to be extending PDUFA dates quite regularly.

So how are we doing? There are a few things to look at.

New Molecular Entity Approvals – The most obvious is to see how we are doing on new molecular approvals – those approvals representing entirely new treatments. Looking at past years and where we were at the mid-year point and where we ended up each year, can give us some insight into this year. The news is not so hot. By the end of June this year, FDA had approved only 16 novel drugs. By this time last year, there were 27. Below is a chart that compares year by year the rate of novel approvals as of the end of April and by the end of year.

This is not to say that the balance of the year might not make up for the slow first half. by mid-year 2019, there were only 13 approvals of new entities but the year netted out with a respectable 48. It all depends on what’s in the pipelineSo let’s look at PDUFA dates.

2. PDUFA Dates– PDUFA dates are proprietary and FDA does not publish a list of upcoming dates. Still, one can compile a list by capturing public announcements of new drug or biologic applications with FDA, many of which mention the specific PDUFA date and many that allow a guess based on counting from the date of a press release. Subtracting out applications for supplemental applications, there do not appear to be an overwhelming number of upcoming dates, which might undermine any recovery in the second half of the year to a more robust number of approvals of new molecular entities.

3. AdComms – Finally, as noted in a prior posting, the number of advisory committee meetings that FDA has been holding has diminished considerably overall. That means that the agency is utilizing outside counsel less frequently, perhaps due in some part to the advent of breakthrough therapy designations which means that the agency is having a higher level of interaction with drug sponsors that may negate the need for an AdComm. But one could also surmise that AdComms are reserved for circumstances where FDA wants outside counsel because an investigative compound is exploring new territory. In any case, the only recent advisory committee was one of the Cellular, Tissue, and Gene Therapy Advisory Committee which by its nature, is likely to be in regard to a new molecular entity.

In short, the outlook for output this year does not appear at this juncture to be promising. But there are many moving parts and when and if they do move, it can change the picture considerably. Certainly there have been years past where at mid-year, there was not a robust output, but which ended up much improved over the final half of the year.

Enforcement Update: OPDP Issues Untitled Letter

We are four months into the year, and this week OPDP has issued its fourth regulatory action letter of 2022. Two of the previous were Warning Letters, considered the more serious of the two categories, and two, including the latest, were Untitled Letters.

As noted in past updates, FDA’s OPDP enforcement letters have dropped off considerably over the years. In fact, over the past two years, the office issued only a total of 6 letters which means 2022 is going at a heightened clip. Of course, if OPDP only issues two more actions for this year, it would be on par with the recent track record – and sometimes several weeks can go by before OPDP issues a letter.

I like to take an approach to examine both the historical context and the substance of each individual letter.

The Letter. The recipient of the letter was Bausch Health Companies and it was in regard to two different communications vehicles – one a “DTC video” that appeared on Lifetime TV’s The Balancing Act – and the other the efficacy webpage of the healthcare professional website. The medicine that was the subject of these communications was DUOBRII (halobetasol propionate and tazarotene) a topical lotion indicated for the treatment of plaque psoriasis in adults. The risk profile of this medicine includes contraindication in pregnancy as well as risk of sunburn among other stated risks.

Taking the video first, there were a couple of things. First was the most common violation cited in OPDP letters – the presentation of risk information. The agency stated that material facts about the risks were not properly conveyed with particular regard to advising women about the risks during pregnancy and noted that the package insert advises a pregnancy test within 2 weeks prior to therapy initiation and advises on the use of contraception during treatment. The video portrayed a women of child bearing age – with two children – making the statement that she used the product during a flare up, implying it can be used any time. FDA did acknowledge the presence of information regarding fetal risk is present in the video, but indicated that the lack of specific reference to the need for testing and use of birth control were material. In addition, the patient in the video is depicted out of doors with exposed shoulders and arms, but did not mention the photosensitivity and risk of sunburn in the video. Finally on the issue of balance, FDA noted that the additional risks were addressed in small text at the bottom of the screen while benefits were being conveyed verbally by a narrator.

The other issue for the video was making an unsubstantiated claim regarding efficacy and an implication of superiority. The video stated that the medicine was the “first and only” topical combining two active ingredients, while FDA asserted that there was at least one other such combination. In addition, the patient depicted said that she had tried other creams that did not work for her. FDA said clinical superiority had not been established and that the statement implied that the medicine would be effective in patients who failed to respond to other treatments. While it may be accurate for this patient in particular, the agency said it could not be broadly applied to all patients.

When it came to the webpage, FDA took issue with language that made the claim of “superior efficacy” to mono therapies based on evidence that was characterized by the agency as a post hoc analysis of a single phase 2 trial not designed to support this type of conclusion.

The Context. It is important to look at context to see if there are any emerging patterns related to enforcement with respect to treatment categories, companies or communications vehicles. There are a couple of things of note. First OPDP enforcement over the past few years has not only diminished, but the actions have generally involved smaller, lesser well-known companies. However of the 11 letters (both Warning and Untitled) sent since 2021 began, Some larger, established companies have been included – such as Amgen and Lilly (which received 2 letters). Also of note, the treatment of pain, in particular migraine, was the subject of 3 of these 11 letters. But perhaps most noteworthy is the fact that the most common communications vehicle that was the target of enforcement were DTC videos which were the subject of 5 of the 11 letters.

Finally, it is noteworthy perhaps that OPDP acquired new leadership last year. That may mean an emerging difference in the way the office engages in enforcement.

Until next time.

Image by Goh Rhy Yan at Unsplash

New Landscape for the Old Pandemic

Tectonic pandemic plates are shifting respecting the COVID-19 pandemic. For weeks now we have been watching caseloads in the United States broadly fall. It feels as if we are indeed shifting gears. There are other moving parts that are in motion as well. It is a fundamental re-shifting of the landscape. And there are consequences.

First, government funding supporting access to vaccination and treatment for COVID has run out and so far, is not replenished. The government established program to fund access for the uninsured has stopped accepting reimbursement claims for treatment and will stop shortly for vaccines (on April 5). For the insured and affluent, not much of a problem. For those without, it can become a major roadblock. And if you need therapeutics, the same problem, but with harsher consequences, especially once the federally purchased stockpiles of therapeutics and vaccines are gone.

Second, next week an FDA Advisory Committee had scheduled a meeting for April 6 (the day after the government program will stop accepting claims for vaccines) to consider whether or not to authorize use of two of the COVID-19 vaccines as a “second booster” or actually a fourth shot, either for people over 50 years or for everyone. Then on March 29, FDA issued an authorization for use prior to the meeting of the advisory committee, quickly followed by a supporting update for providers to permit access from CDC. A fourth shot will likely be authorized by CDC, though access may be different than in the past, especially after the government stockpile recedes.

Third, the BA.2 sub variant 0f Omicron is poised to cause an increase in U.S. caseloads as it has in other parts of the world, thought it is not certain when. According to the Centers for Disease Control (CDC) it is now the dominant strain. After weeks of falling caseloads, some areas like New York City and New York State have seen the rates per 100,000 start to rise again and the 14-day change in cases has risen 92 and 78 percent, respectively as of yesterday, and have been increasing for the past several days. With the fourth booster in hand, those most vulnerable might opt to take it now (while there is stockpile) only to see it wane if the BA.2 wave in the U.S. does not happen until later in the year.

Fourth, the rise in availability of home testing is likely masking (pun intended) the actual numbers. Whole families may be find they are feeling unwell, testing and finding they are sick, but never getting sick enough to get medical attention. So they are completely under the radar when it comes to the numbers that we are counting and upon which we are basing policy decisions, like mask requirements.

Fifth, the masks are dropping. Attending a theatre performance this weekend I was double bagged – a KN95 underneath and a second (more fashionable) cloth mask over it. But I was in the minority by far. The lowering of mask requirements and inclinations may spur the emergence of the sub variant, or future variants.

Sixth, speaking of new variants, in places around the globe where there large numbers of people are being infected there is a potential fro the development of new variants.

In short, we are being dealt a new hand. A more spreadable virus is among us just as our vigilance is waning. More vaccine doses are authorized, but access is narrowed. Cases are increasing while mortality – a lagging indicator – has dropped. And perhaps most important, we are not assuring widespread access to vaccines and treatments to the most vulnerable, we are not accurately counting, and we are not taking precautions. From a policy perspective, perhaps we needed a new hand, but one thing remains – in the face of on-going infection, access to vaccines and therapeutics remains essential. While we are looking at a new landscape, we are also facing certain obstacles.

Photo by Casey Horner on Unsplash

Are We Moving On From Covid?

Mask mandates are dropping like flies. Restrictions are being lowered. In my observation, it feels that they are going to the wayside not only because of dropping caseloads, but also because people are just more than ready to move on. There may be some complacence – a feeling that the ubiquitous Omicron has fostered a feeling of inevitability about exposure and eventual infection. But mostly, we are just tired – there is a strong sense of COVID fatigue, not just among people, but it seems even institutions.

Even perhaps FDA. In a recent blog posting, I looked back at the profile of FDA press releases over the period 2013-2021 (See What They Said 2021 – An Overview of FDA Press Statements). In it we saw that FDA had a good deal to say in 2020 putting out over 400 press statements, but that output fell considerably in 2021.

Not only was the agency saying less, it was saying less about COVID. Communications regarding aspects of agency work vis a vis the pandemic fell in 2021 compared to the year before, despite the number of developments in vaccines and therapeutics during the year. Looking at it on a month by month basis, you get a real impression of how much oxygen COVID-19 took of FDA’s communications.

COVID-related releases are indicated in orange while non-COVID are in blue. Looking to the right axis of the graph above, one can see that during 2020, COVID was over 50 percent of the discussion nearly all of the time. In April 2020, COVID-related statements comprised three quarters of FDA’s public facing releases, and it never went below 50 percent during the rest of the year. By contrast during 2021 there were some spikes, but the overall profile of COVID talk fell below the 50 percent mark during several months. And the first month 2022 (not a big month for press statements from the agency in general) saw a steep decline. The overall trend is definitely downward.

Why is this important? It may not be, but it also may be a signal from a communications perspective that it may be easier to get back to some of the topics – and some of the science – that we have maybe pushed aside for the past two years. Maybe there is opportunity to talk about the cancer moonshot, or the goal of ending HIV/AIDS or other pressing issues from which we were distracted#C.

Perhaps the pandemic is becoming normalized, perhaps we are just tired, or could there be less actually happening? Maybe it is a combination of all three. It is likely too early to tell. Certainly there are many mysteries remaining with respect to what it means to have COVID, to prevent it and to treat it and many more with respect to what it has done to us as individuals and collectively. But it would be nice to get back to other topics. We will have to see.

Photo by Isaac Quesada on Unsplash

OPDP Issues First Regulatory Action Letter of 2022

FDA’s Office of Prescription Drug Promotion (OPDP) issued the first regulatory action letter for 2022. This one has some notable characteristics.

As has been frequently noted, enforcement actions by OPDP have diminished considerably over the years. Another characteristic of recent enforcement actions over the past several years is that smaller, less well-known companies have mostly been the recipients of letters from OPDP. That said, the last two letters – the final one of 2021 and the first of 2022 both went to the same company – Lilly. Here are a few other facts to put this letter into context:

This one, as was the last one, is an Untitled Letter, considered the less serious of the two types of letters sent out by OPDP; The product involved was one for diabetes, one of 7 letters issued since 2003 by OPDP regarding a diabetes product covering 10 different communications vehicles (in 2009 GSK received a letter covering 3 sponsored links for separate products); The communications vehicle that was the subject of this letter was an Instagram Post, one of two social media violations related to diabetes over the past several years (the first was a Facebook posting for Mannheim’s Affrezza); It is the second time FDA has taken action in relation to an Instagram posting, the first having been issued in 2015 regarding a product for morning sickness.

So why did OPDP act upon this Instagram post? According to the letter, the agency noted first of all that the video that was part of the Instagram post stated that Trulicity could “lower A1C along with diet and exercise” but that the Medication Guide specifically states that the drug is used for people with type 2 diabetes. There were additional limitations to the use of the drug, including that it is not recommended for people with severe stomach or intestinal problems, nor should it be used in people with type 1 diabetes. Therefore, the agency said, the indication was not adequately communicated. Moreover, when it came to risk information, OPDP noted that the benefits of Trulicity were emphasized through “attention-grabbing” and fast-paced video, but the the risk information was presented was included in a small window that was difficult to read and therefore presented a challenge in comprehension. In addition, one of the side effects regarding hypoglycemia that was in the Medication Guide did not appear in the posting, leaving the overall presentation minimizing risk associated with use. FDA noted that the product has a boxed warning and that there have been past advisory communications from FDA have expressed concerns.

It is perhaps worth noting that while this violation involved a communication via a social media platform, the issues addressed in the letter were not because it was a social media platform. Essentially, OPDP said, a video lacked balance and omitted some material issues. It was not the medium, it was the message.

As you may recall from recent postings, last year FDA decided to remove Warning Letters, considered a more serious infraction, from the list of OPDP regulatory actions. The above chart portrays a combination of Untitled Letters and Warning Letters. However, FDA now lists Warning Letters in a searchable part of the FDA website that lists all Warning Letters issued by any part of the agency, while the OPDP portion of the website now only lists Untitled Letters. This means that in order to get an understanding of all the actions taken by OPDP, you now must consult two different parts of the FDA website. Confused? Well, yes, it is in confusing. Warning Letters can be found performing a search here, while Untitled Letters are listed here.

Eye on FDA maintains a database that contains the results of Warning and Untitled letters issued by OPDP going back through 2003. It includes 352 letters covering over 450 communications vehicles and over 1100 violations. The database tracks disease area, type of communications vehicle, whether or not the product had a boxed warning, whether or not it involved a Warning or Untitled Letter, whether it was a digital or traditional communications property and of course, the violations cited in the letter.

Note: In a prior posting reviewing 2021 regulatory actions, it was stated that FDA issued 5 regulatory action letters for the year. Since that writing, FDA posted another letter in mid-January that was sent to a company on December 19. That posting has been updated to reflect the late addition from FDA.

Photo by Goy Rhy Yan on Unsplash

What They Said 2021 – An Overview of FDA Press Statements

Each year we look back to take stock of how the agency has been communicating in the course of the previous year and assess how that might compare to years gone by. In fact from year to year, there is a good deal of change that occurs. When Dr. Scott Gottlieb took the reins of FDA as Commissioner, the amount of communications material put out jumped enormously. And it did so again last year when the agency would have a lot to say about COVID-related activities.

This year, however, not only was the agency putting out less, the number of releases this past year represents a somewhat inflated number. In prior years, the agency statements under a heading called “FDA in Brief“. These are statements that differ in format and nature from a traditional press release. They are more general announcements than they are news. Press Releases announce approvals, for example, while FDA in Brief statements can be used to “remind industry” or to announce that the agency will be holding a meeting. Press releases are often (though not always) released in English and Spanish, while FDA in Brief statements are not. These statements were housed on the FDA website separately from press releases. This year, however, the agency not only listed the FDA in Brief statements under their own heading, they also begin listing them in with the press releases they agency sends out. Since they did not do this in years gone by, that means that the number represented in the press release category is inflated. This year there were 43 “FDA in Brief” statements included in with press releases. If you actually removed them from the count, then the actual number of traditional press releases from FDA this year is 241, meaning the agency issued about 57 percent of the releases they issued during 2020.

Why the plunge? Certainly there was a good deal going on related to COVID, and the agency also approved a solid number of new molecular entities during, falling just a few shy of last year’s record number. One possibility may be the presence (or not) of a full time commissioner. The arrival of Dr. Gottlieb certainly saw an impact in volume. During nearly all of 2021, FDA has been under the direction of an acting commissioner.

In any case, here is what FDA talked about this year.

COVID – 144 announcements were COVID-related in 2021, compared to 274 such announcements during 2020;Approvals – there were 77 announcements related to approvals this year, 22 of which were COVID-related announcements. In 2020 there were 40 COVID-related approval announcements. There were 43 drug and gene therapy approval announcements in 2021 (7 of which involved EUA announcements), 24 device approval announcements (7 of which were COVID-related) and 8 announcements related to Vaccines;Alerts – there were 9 Alerts issued by the agency this year, 4 of which were related to COVID – this compares to 16 Alerts issued in 2020, 7 of which were related to COVID;Legal – there were fewer releases related to legal issues in 2021, with only 12 issued regarding warnings issued by the agency or consent decrees compared to 21 in 2020;General Announcements – this category includes statements from the commissioner or from various division heads and here is where there the greatest numerical difference existed between 2020 and 2021. In 2020, there were 251 such pronouncements while in 2021 there were 156;Translation – Sometimes FDA communications are issued in both English and Spanish, sometimes not. There is no discernible rhyme or reason to it. There is also no indication why all communications are not translated. The translation rate appears roughly the same for the past two years – in 2021, 57 of the 284 releases (20 percent) were translated into Spanish, compared to 88 of the 420 last year (21 percent).

As far as what 2022 will bring, given the events of the past two years, it is hard to say. If the pipeline continues to produce in spite of the pandemic, there will be new approval announcements. There will certainly be new COVID developments. And the existence of so many products authorized under emergency use authorization is certainly an issue that will have to be dealt with. When will the products be fully approved? And while the imprint of the communications style of a new commissioner is something that might be anticipated, we are getting a commissioner who we had once before in 2016-2017, a period where the quantity of communications was not robust. And new in 2022, FDA has occasionally begun issuing something called “FDA Roundups” but have provided to date no new “FDA in Brief” statements. Something to keep an eye on.

Photo by AbsolutVision on Unsplash

FDA OPDP Look Back at 2021 – The Yawning Gap

Once again it was a quiet year with respect to the FDA’s Office of Prescription Drug Programs (OPDP). As noted in the past, there are two primary means for understanding the agency’s latest thinking with respect to promotional communications from pharmaceutical companies – the content and pattern of enforcement and the issuance of guidance documents to shed light on the parameters that exist. In that respect, 2021 was not a banner year.

The Numbers: Looking first at the quantity of enforcement, the numbers were low. This year there were 5 regulatory action letters issued by OPDP. The only other time in the past 24 years when enforcement was this low was in 2017. This year there two were Warning Letters and three were Untitled Letters.

The 5 letters issued involved 8 different communications vehicles for a total of 9 violations that were cited by the agency as reasons for the action.

The Substance: What triggered the enforcement actions? Back in 2009 you may recall that FDA issued 45 Untitled Letters aimed at 14 companies regarding the use of banner ads/sponsored links where clearly benefits of a branded product were available, but risk information only ascertainable by clicking on a link. This was a clear direction from the agency that risk information could not be incorporated by link. This year, three of the communications vehicles involved in enforcement actions were either banner ads or sponsored links where risk information was not included. One of them involved the more serious Warning Letter action, possibly because the product associated with that communication had a Boxed Warning in its label. The other communications vehicles involved DTC videos. Of the 9 violations that were cited in the 5 letters, 4 were for risk minimization or omission, 2 involved superiority claims, 1 unsubstantiated claim and 2 failure to submit Form 2253 to review.

Guidance Docs: As far as I can see, there have been no new relevant guidance documents, wither in draft or final form, that are focused on digital and/or social media and promotional communications. In the latest published guidance agenda from the Center for Drug Evaluation and Research, the advertising and promotion category had no slated guidance efforts listed.

Research. To a degree OPDP signals where it is headed in terms of enforcement and guidance by telling us what research it is conducting around promotional communications. Of the 13 projects currently underway by OPDP, 2 of them are focused on aspects of television DTC ads. There is one study comparing physician interpretation of information from scientific publications versus promotional materials. And curiously, one study is focused on assessing medical conference attendee observations about prescription drug promotion even though medical conferences have largely been virtual for the past two years. None of the studies underway are aimed at uncovering data that would be helpful in providing additional guidance related to the use of digital and social platforms by patients, prescribers and pharma companies.

Why This is a Fail. The way that patients and prescribers learn about medicine has changed significantly over the past 15 years. People do still watch commercial television, but in fewer and fewer numbers. Digital and social media are a primary resource for getting healthcare information and discussing treatment, especially now in the age of COVID. It is a continually evolving environment – there have even been an abundance of articles about how pharma companies should be using TikTok. In particular, for people who do not have access to computers, mobile access is the primary means of getting information. How websites are optimized for mobile is therefore important. FDA has traditionally taken the view that if it is wrong on television DTC, then it is wrong on TikTok. But these are all new platforms that have a lot of nuance to the use of the platforms, in addition to the fact that different populations may have different approaches to digital consumption as well as varied skills. There may be vast comprehension differences in digesting communications from digital sources than from traditional DTC television advertising. It is way past time for the agency to have applied effort to understand the role of that nuance and to make more detailed studies – and therefore guidance – on the best uses of digital media. And of course, there is the fact that FDA never really finished providing guidance related to social media inaugurated by the public meeting the agency held in Washington, D.C. in November 2009. At that meeting, the agency posed five questions as a framework for developing a guidance the following year. Guidance did not come for five years and then did not follow the framework, leaving the questions only partially addressed by two guidance documents – one on use of platforms with character space limitations and another on correcting misinformation posted by third parties. This leaves quite a bit of work not done as it relates to social and digital media, the source from which growing numbers of people get health care information.

FDA Changes Display of Warning/Untitled Letters. Finally, FDA has made it harder to get a view of the regulatory actions with respect to promotion. All letters, Warning and Untitled Letters used to be listed in chronological order. This year, for reasons that are incomprehensible, FDA moved the Warning Letters from the list of OPDP actions and lumped them into all of the other warning letters issued by the entire agency. Now to assess the activity of OPDP for the year, one must visit the list of Untitled Letters and then sort through the list of agency-wide warning letters.

One thing that did happen this year is that OPDP has new leadership. It takes a long time to steer any ships within an agency as large as FDA and to bring about true change. The gears grind slowly. But there is a yawning gap between communications realities on the one hand and the agency focus when it comes to promotional communications. One hopes that the agency will consider the shifts in communications that have taken place and the impact those shifts have on the decisions that patients and providers make with respect to treatment. Hopefully 2022 will bring greater attention to addressing the many deficits that exist in the current approach to enforcement by conducting more research that is appropriate to the communications environment.