Blinded by Science: The Importance of RWD and Post-Market Surveillance

The popularity of GLP-1 drugs has everyone talking about them, from Senela Williams' hype to South Park's satire.

This heightened focus has put a spotlight on every aspect of the treatment, from the profound role it plays in improving people's ability to manage obesity and cardiovascular risk, to signs of potential side effects and risks not revealed in clinical studies.

Regarding the latter aspect, GLP-1 provides an important reminder of an important and often underestimated aspect of any drug or medical development: ongoing post-marketing surveillance.

This critical development phase after a drug is released allows pharmaceutical companies (as well as the FDA and other regulatory agencies) to actively monitor the safety, effectiveness, and use of new treatments in the “real world.” This assessment is critical to understanding use in different populations, the experiences of off-label and special groups, and identifying issues that may have been missed in clinical trials, such as rare or long-term adverse effects.

Recent advances in artificial intelligence are aiding these post-market surveillance efforts.

Teams of medical and technical experts are using AI-driven technologies to significantly enhance the ability of researchers and regulatory agencies to obtain meaningful large volumes of data or real-world data, supporting important observations and decisions that improve drug safety and healthcare outcomes for all.

Inspiring Cases of GLP-1s

GLP-1 drugs are a class of drugs that mimic the effects of the natural glucagon-like peptide-1 (GLP-1) hormone, which is released from the intestine after eating and are designed to treat type 2 diabetes. Like many drugs, they have found secondary, and in some cases off-label, uses separate from their original clinical focus.

They are now used to reduce cardiovascular risk and manage obesity by helping to control blood sugar levels, promoting satiety to reduce appetite and slowing gastric emptying.

There's no doubt that GLP-1 is changing lives, and the weight-loss drug's popularity has soared, fueled by a social media frenzy. Recent studies indicate that approximately 12% of U.S. adults have used GLP-1 drugs.

As with most relatively new treatments, continued use and emerging data reveal a more complete picture, from effectiveness to side effects. In the case of GLP1, there is evidence of unexpected benefits and risks.

unforeseen consequences

While studies suggest a possible protective effect against glaucoma and a reduced risk of wet age-related macular degeneration (AMD), other studies suggest a higher risk for neovascular AMD. Additionally, some patients have developed vision problems, including nonarteritic anterior ischemic optic neuropathy (NAION), while taking these medications.

Lawsuits filed against the manufacturers of the GLP-1 receptor agonists semaglutide (Ozempic, Wegovy) and tezeparatide (Mounjaro, Zepbound) allege that the drugs have caused blindness and vision loss. A central claim in these cases is that drug companies failed to adequately warn patients and doctors about potential eye risks.

Recent peer-reviewed studies and global pharmacovigilance data indicate that GLP-1 may significantly increase the risk of vision-threatening diseases such as non-arteritic anterior ischemic optic neuropathy (NAION) and neovascular age-related macular degeneration (nAMD).

Although US FDA FAERS and WHO VigiBase show an unusually high rate of vision-related adverse events among GLP-1 users, the results of a recent study in the American Journal of Ophthalmology do not support an association between NAION and GLP-1.

According to the American Academy of Ophthalmology and the North American Neuro-Ophthalmology Society (NANOS), for patients who experience the “very rare” side effect of vision loss associated with NAION while taking GLP-1, discontinuing treatment may pose a significant health risk to the patient's overall health.

Conflicting findings and blind pots

These Conflicting study results for new drugs are common and can result from a variety of issues related to trial design, diverse patient populations, and more. Multiple variables can confound studies of links between new drugs and eye disease. Because patients taking GLP-1 often have severe or long-standing diabetes and obesity, underlying health problems and their associated risk factors are major confounders.

The lack of extensive postmarketing data for new drugs can lead to regulatory blind spots. Because safety data are limited, more comprehensive information is necessary.

Although GLP-1 safety studies are well designed and provide meaningful insights, they are not necessarily the final answer. Many of these studies have limitations that may affect their generalizability and clinical significance. Without sufficient follow-up data, it will be difficult to answer many questions: Are there actually beneficial and/or adverse longitudinal effects? Does early deterioration mask later stabilization?

Reality: The Importance of Post-Market Surveillance

Real-world data (RWD) provide a window into adverse events in diverse patient populations, including groups historically underrepresented in randomized controlled trials (RCTs), such as the elderly, racial and ethnic groups, and patients with multiple comorbidities. RWD also provides evidence of long-term effectiveness.

RCTs typically measure outcomes over months or years, whereas RWDs can analyze the durability of treatment effects, adherence patterns, and the effectiveness of a health care facility over duration—critically important for GLP-1. Rare adverse events may be missed when the incidence of disease is too low to be captured in a typically sized clinical trial. This is why impartial post-market surveillance following the approval of new drugs is critical.

By capturing safety and efficacy in diverse, long-term, and unselected patient groups, RWD complements trial evidence and ensures comparisons are fair, contextual, and clinically meaningful.

All drugs require careful and ongoing post-marketing surveillance, especially if used off-label. A major challenge with any off-label use of a medication stems from the lack of strong clinical evidence for the unapproved indication. Off-label use of drugs is associated with a significantly increased likelihood of adverse drug events (ADEs), often resulting from use in vulnerable populations that were not included in the original clinical trials.

A new era for RWD

AI-driven tools bring new capabilities to processing and managing RWD, particularly unstructured data such as clinical notes in electronic health records (EHRs).

When used with a rigorous subject matter expert guidance process, AI-curated RWD is an important resource that provides life sciences organizations with new power to monitor the various ways in which drugs are actually used post-approval.

This development represents an important advance in post-market surveillance. Understanding the longitudinal safety impact of new therapies, and their effects in combination with other drugs and real-world conditions, has profound implications not only for patients but also for life sciences organizations.

Maximizing the value of AI-driven capabilities to search for emerging safety signals in RWD and identify and assess unexpected benefits or harms as quickly as possible is critical to taking timely action to promote patient welfare and protect our healthcare system.

Photo: phive2015, Getty Images

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