What the US regulator reviews and acts on
Between 2009 and 2019 the US Food and Drug Administration reviewed prescription drug promotion against tests set by statute, acted on a list of named violations, limited what a company could say about a product before its approval, and applied its rules to how an advertisement is presented, to promotion online and to the reprints that sales representatives hand out.
The promotion office and its review
In 2012 the agency regulated the labelling of over-the-counter medicines, and the Federal Trade Commission regulated their advertisements. For prescription medicines the agency's Office of Prescription Drug Promotion regulated audio, video and printed matter, which can include brochures, booklets, mailing pieces, exhibits and slides, supplied or disseminated by the manufacturer, distributor, packer or any other party acting on behalf of the sponsor. All promotional labelling had to be accompanied by the prescribing information. The office had a consumer division and a professional division for promotional material. One of its divisions was the Division of Professional Drug Promotion.
The office's authority came from the federal Food, Drug, and Cosmetic Act, which sets four tests: prescription drug promotion must not be false or misleading, must have fair balance, must be consistent with the approved package labelling or prescribing information, and must include only claims substantiated by adequate and well-controlled clinical studies or substantial clinical experience.
The office received about 70,000 submissions a year of FDA Form 2253, the transmittal form that must accompany each submission of advertisements and promotional labelling for a drug product. The Code of Federal Regulations requires all advertisements and promotional labelling to be submitted, with that form, when they are initially published or disseminated. With a staff of 100 the office was unable to review each submission in great depth, so it screened the submissions for egregious violations of the Act and the regulations and tried to prioritise its actions on what it saw.
The US regulatory environment affects the development of the materials that medical communicators prepare and submit. Regulators such as the Food and Drug Administration expect companies and their agents, who include medical writers paid by a company, to follow the regulations for promoting drugs and medical devices. A company may not make promotional claims that are inconsistent with the labelling, or that suggest a drug or device is safe and effective for a use that is not in the approved labelling. Anyone who communicates about a prescription product therefore has to understand what product labelling is and how to make compliant claims that the labelling supports, which includes the use of market research, competitor information, patient quality-of-life data and disclaimers, among other areas. In 2018 the Food and Drug Administration had a well-established enforcement program against companies and individuals who violate the law and regulations governing promotion.
The office's don'ts and dos
In 2012 a speaker from the office set out the don'ts of prescription drug advertising.
- Do not frame or omit risk, completely or partially. Risk information must be provided in promotional material that makes product claims, and it should include contraindications, warnings, precautions and pertinent adverse events. Presenting a risk as a benefit violates the regulations: where a product has an adverse reaction of weight loss, a branded piece that adds that a patient can lose weight on the product frames a risk as a benefit.
- Do not minimise risk. Examples are omitting material information about a risk described in the approved labelling, putting non-risk information in a risk section or the reverse, listing risk information as a benefit, and presenting risk inappropriately through framing, layout or prominence, and sequencing. Sequencing means that the most serious risks should be presented first.
- Do not use misleading characterisation, that is, broaden the indication. This means implying that a drug is useful in a broader population of patients or range of disease states than has been demonstrated, and it includes failing to disclose the full indication with its limitations.
- Do not overstate efficacy by suggesting or representing the drug to be more efficacious than has been demonstrated. Overstating can also occur by guaranteeing efficacy, claiming a faster onset of action, or making claims about survival or long-term outcome.
- Do not make superiority claims, which are comparisons that represent or suggest, by implication or directly, that a drug is safer or more effective than another drug. The standard of evidence for a superiority claim is a head-to-head clinical trial. A generic medicine must demonstrate bioequivalence and cannot make a superiority claim without the results of a head-to-head trial.
- Do not make a misleading claim about the mechanism of action, which could be suggesting a greater understanding of the mechanism than actually exists.
- Other don'ts: do not omit or minimise a drug's prescription status, promote unapproved uses, use unsubstantiated convenience claims, or fail to submit the promotional material at the time of first use.
In 2018, failure to disclose risk information adequately was the number one reason companies received enforcement letters, and a piece must leave an accurate and non-misleading impression of both the product's benefits and its risks.
At a meeting on 24 and 25 February 2009, comparison of products was reported to remain an area of concern in promotion. Discussion of a study that directly compares the safety and efficacy of two products was allowed, but comparing two separate studies to draw conclusions about a product was a problem: because the patient populations, dosing and other parameters may vary, there were few situations in which such a comparison was allowable.
In 2012 the same speaker from the office set out the dos of prescription drug advertising.
- Review and apply the federal Food, Drug, and Cosmetic Act and the Code of Federal Regulations.
- Review guidances, enforcement actions, the office's website and the approved prescribing information. Look over competitors' prescribing information and the complaints that have been filed about promotional materials for relevant drugs.
- Meet the standard for substantial evidence. The regulatory definition of substantial evidence for efficacy claims is generally two adequate, well-controlled clinical trials. Substantial evidence is required to support claims in the prescribing information, and the same level of evidence is required to support claims in promotional materials. Claims outside the prescribing information can be substantiated.
- Communicate with the office as needed. The office offers information on its website, through its guidances and through outreach that includes conferences, trade press and webinars. Its quarterly webinars are a forum for looking at enforcement actions and asking questions.
- Seek advisory letters from the office. An advisory letter gives the office's opinion about a marketing campaign or a claim before it is publicly disseminated. Seeking one is voluntary and confidential, and is a subpart H exception; subpart H is the agency's accelerated approval of new drugs for serious or life-threatening illnesses, enacted in 2002.
- "Do communicate with OPDP enforcement letters." Unlike advisory letters, enforcement letters concern pieces in the public domain and are public. An enforcement letter can be untitled or, for more egregious or repeat violations, a warning letter. A letter carries the expectation that the violative claims and presentations stop immediately, and whoever receives a warning letter is expected to respond with a corrective message.
What may be said before approval
The Food and Drug Administration recognises that scientists must share information, and that the public and investors are entitled to scientific information as it evolves, before a product is approved. To address this it permits "scientific exchange", which concerns writers who work on data communications: a company may discuss scientific data on a prescription product before approval if the information is objective, fairly balanced and includes balancing risk information. At no point before approval may the company claim that the drug or device is safe and effective. When such exchange is non-promotional in nature, it is regarded as acceptable from an enforcement standpoint and is known unofficially as a "safe harbor": the circumstances in which the agency is not likely to take enforcement action.
How an advertisement's presentation is judged
In 2009 the Food and Drug Administration published draft guidance on the criteria it uses in evaluating advertisements and promotional labelling for prescription drugs and medical devices. The draft says what to consider when developing a print or audiovisual advertisement, and its considerations range from the framing of information to whether the music in a television advertisement stays at a constant volume while risks are discussed as against benefits. It also shows a health care consumer what to beware of when weighing an advertisement's claims. Even when finalised, the agency's guidance documents do not establish legally enforceable responsibilities.
The Food and Drug Administration Amendments Act of 2007 requires a television or radio advertisement for a drug to be "clear, conspicuous, and neutral". In 2010 the agency proposed four standards for manufacturers to use in deciding whether those criteria are met: the major statement, which is the information about risks, contraindications and efficacy, must be readily understandable by consumers; audio information must be understandable in volume, articulation and pacing; textual information must be placed appropriately, presented against a contrasting background and set in a readable font size and style; and the advertisement may not include statements, text, images or sounds that detract from the major statement. The standards were a proposed rule open to comment.
Promotion on the internet and social media
In February 2009 a panel of representatives from each branch of the agency said that transparency and strict adherence to the package insert in all promotional activities were key to avoiding letters from the agency. Non-traditional internet-based marketing tactics, which were increasing, were a point of concern for the panel: however casually Facebook, YouTube and other internet sites are treated elsewhere, the same rules apply to promotion on the internet as in print or other media.
In 2009 the agency held two days of talks on the digital and electronic marketing of health care products and services, including advertisers' use of social media to interact with patients, and promised to release guidelines; in March 2011 it said that more studies were needed. In June 2011 the Digital Health Coalition was launched as "a national public forum for the discussion of the current and future issues relevant to digital and electronic marketing of health care products and services". Major pharmaceutical companies, advertising agencies, health information companies and Google decided to convene roundtables and webinars and to publish white papers, and they invited input from a wide range of stakeholders.
The Food and Drug Administration Safety and Innovation Act of 2012 required the agency to give industry guidance on the use of social media to promote regulated drugs and medical devices. The agency agreed at that time to develop guidances on four topics: meeting regulatory requirements on platforms that have character or space limitations; meeting all postmarketing submission requirements on social media platforms, including the use of internet links; defining the kinds of online communication that manufacturers, packers or distributors are responsible for; and correcting online misinformation from independent third parties. Its response came in 2014 as three guidances aimed at helping companies and their representatives communicate accurately online about their medical products: on the promotion of regulated medical products through social media, on the correction of independent third-party misinformation, and on the presentation of risk and benefit information on platforms that have character space limitations.
The first draft guidance, issued in January, set out new requirements for submitting interactive online promotional material to the agency: who is responsible for the online content, which parts of it have to be submitted, and when. A company was responsible for submitting the static and interactive promotional material on a site that it managed. A site counted as managed if it "is owned, controlled, created, influenced, or operated by or on behalf of a company", which included a third-party site where the company collaborated on the promotional material or edited, reviewed or had review privileges over it, even where those activities were limited in scope. Financial support of a site alone, without the ability to manage it, did not necessarily indicate control or influence, and a company that did not meet the requirements for managing a site was responsible only for submitting the promotional content it had provided to the site. A company was also responsible for the user-generated content of an employee or agent acting on its behalf, an agent being anyone acting on behalf of the company, which includes direct employees, contractors and subcontractors. The agency suggested that if an employee or agent commented on a third-party website about the company's product, the company was responsible for the content.
The guidance matters especially to medical writers who engage in social media on their own websites, because a company was considered responsible for the content on a writer's website if the writer was acting as its agent, even where the company did not meet the criteria for managing the site. A medical writer writing an independent blog or posting online content should be aware of the legal limitations they face. By 2015 some courts had held that medical writers who blog are entitled to the same free-speech protections as news journalists.
The first draft set out a submission process and its timing for interactive promotional material. For a site whose content a company was responsible for, it called for an initial display of the comprehensive static product website with its interactive real-time components, annotated; a submission after any change to the product website, annotated; and monthly screenshot updates of the real-time components. For a third-party site in which the company's participation was limited to interactive communications, it called for a screenshot of the site's home page with the interactive page and the company's first communication, and no screenshot for monthly updates. Monthly updates for non-restricted sites were an updated listing of all the non-restricted sites that the company was responsible for or an active participant in, including all real-time interactions. Monthly updates for restricted sites were all content related to any online discussion, for review, with screenshots of all real-time interactions.
The second draft guidance, issued in June, dealt with misinformation about a company's own approved products that an independent third party creates or shares on the internet or social media, and defined misinformation as "positive or negative incorrect representations or implications about a firm's product". Correcting it was voluntary. A company that decided to correct it had to make the correction truthful and not misleading, and could also remove the misinformation or ask the third party to remove it. The draft further recommended that a correction be relevant and responsive to the misinformation, limited and tailored to it, non-promotional in nature, tone and presentation, accurate and consistent with the labelling the agency requires for the product, and supported by sufficient evidence. Companies were not expected to correct all of the misinformation on the internet, but a company that corrected should clearly identify what it was correcting and where the misinformation was found, and should address misinformation that is positive in tone as well as negative, to remain fair and balanced. Where a third party did not remove or correct misinformation after the company had notified it, the agency would not hold the company responsible for the misinformation; the company was to keep a close and accurate record of all its attempts to contact the third party. One writer on the 2014 guidances holds that following the agency's recommendations for correcting misinformation is an excellent way for a medical writer who communicates medical information on the internet to remain truthful and accurate.
The third and final draft guidance of 2014, the second of the two issued in June, addressed platforms that have character space limitations, such as Twitter and online paid searches. The agency's concern was that a post could amount to misbranding if it presented a product's use without disclosing the product's risks. Whatever the space limitation, risk and benefit information had to be balanced to comply with the Food, Drug, and Cosmetic Act, and the agency recommended that a company that could not give all the risk and benefit information within the space should reconsider using the platform. The agency agreed to abbreviations and concise text in such a communication only where a prominent hyperlinked reference gave consumers direct access to the risks associated with the product. It recommended that companies present the actual risks of a product that requires risk information and not merely a link to them, include on an existing product website a page dedicated to risk information, set up obvious URLs for such pages in place of shortened ones, and review each product's indication and risk profile to decide whether information can be developed for space-limited settings at all. The same writer holds that by applying the second principle of the AMWA Code of Ethics, on objectivity, scientific accuracy and rigour, and fair balance in all media, and following the agency's recommendations in this guidance, medical writers can participate on such platforms without fear of harming their employers' or their own reputations when discussing product information.
The director of the agency's Office of Prescription Drug Promotion described the two June drafts as the agency's current thinking on social media, "not the final word, but rather a work in progress", aimed at ensuring that the information drug and device companies provide is accurate and helps patients to make well-informed decisions with their health care providers. The agency planned to continue reviewing the social media landscape, to develop new approaches to help companies communicate with consumers through the internet, and to create best practices that can be applied to existing websites.
The same writer on the 2014 guidances holds that understanding the agency's current opinion on online communication, together with following the AMWA Code of Ethics, enables medical writers to be conscientious about the information they broadcast through social media and the effect it may have on clients, employers and consumers. The writer also holds that the AMWA code and the agency's position overlap, and acting in accordance with one usually satisfies the other. When a medical writer blogs or engages in social media, it is important that they recognise and observe the statutes and regulations that pertain to the content of the post.
Reprints handed out by sales representatives
By 2009 the Food and Drug Administration had finalised its Good Reprint Practices guidance. The guidance restored sales representatives' prerogative to distribute, but not to discuss, journal articles about off-label uses of drugs. A number of conditions applied, among them that the article must come from a peer-reviewed journal and must be distributed separately from promotional material. Letters to the editor, publication abstracts, reports of phase I studies in healthy subjects and industry-funded literature such as journal supplements were among the publications excluded. The agency said that the guidance does not establish legally enforceable rights.