Google Searches for Thyroid Eye Disease After Regulatory Approval of Teprotumumab

This cross-sectional study investigates the association between direct-to-consumer marketing and information-seeking behavior based on Google Trends.

Key Points

Question

How was direct-to-consumer marketing associated with information-seeking behavior based on Google Trends?

Findings

In this cross-sectional study that used Google Trends to examine patterns in search queries across the US, relative search volumes for thyroid eye disease showed a 525% increase in December 2020 and a 640% increase in May 2021. These months corresponded to the launch of 2 national advertising campaigns by the manufacturer of teprotumumab.

Meaning

These findings suggest that direct-to-consumer advertising campaigns for teprotumumab may have been associated with an increase in public interest for thyroid eye disease.

Abstract

Importance

Given that direct-to-consumer advertising campaigns have the potential to both positively and negatively affect patient care, clinicians would benefit from being conscious of changes in public interest that result from such campaigns.

Objective

To understand how direct-to-consumer advertising was associated with information-seeking behavior based on Google Trends.

Design, Setting, and Participants

This descriptive cross-sectional study used Google Trends to examine relative search volumes for thyroid eye disease (TED) from January 1, 2004, to June 30, 2021, in the US. The data for this cross-sectional study were downloaded on October 17, 2021. This study included internet search engine queries originating within the US, as determined by Google Trends.

Main Outcomes and Measures

Monthly changes in relative search volumes for the terms “thyroid eye disease,” “Tepezza,” and “teprotumumab.”

Results

From January 1, 2004, through June 30, 2019, searches for TED demonstrated a stable baseline level with a mean (SD) relative search volume of 1.78 (1.25). After US Food and Drug Administration approval of teprotumumab in January 2020, TED searches increased by 25%. After the manufacturer of teprotumumab ran its first national television commercial in December 2020, a 525% increase in TED searches was observed. After a second series of national television advertisements for teprotumumab in May 2021, TED searches increased by 640%.

Conclusions and Relevance

Findings of this cross-sectional study suggest that direct-to-consumer advertising campaigns for teprotumumab may have been associated with an increase in internet search traffic for TED. Google Trends may serve as a useful tool for measuring the influence of pharmaceutical advertising campaigns on information-seeking behavior in the public. Additional studies are warranted to determine how these changes in public interest correlate with clinical measures, such as referral patterns.

Introduction

Thyroid eye disease (TED) is an autoimmune condition commonly associated with thyroid dysfunction, which has a clinical presentation ranging from mild disease to irreversible sight-threatening complications.¹ Until recently, medical therapies for TED have been limited largely to systemic glucocorticoids, which are associated with adverse effects.¹ On January 21, 2020, teprotumumab (Tepezza; Horizon Therapeutics) became the first prescription medication to be granted US Food and Drug Administration (FDA) approval for the treatment of TED.²

Before FDA approval of teprotumumab, the drug’s developer, Horizon Therapeutics, launched a multichannel TED awareness campaign, including a website and Facebook community aimed at providing education to patients and caregivers.^3,4 They also launched an early direct-to-consumer advertising (DTCA) campaign shortly after FDA approval of teprotumumab, which expanded to nationally aired television commercials in December 2020.³ The extent to which this campaign influenced public awareness of TED, to our knowledge, has yet to be described.

Google Trends (Google) is an analytical tool that has been increasingly used in medical research to gauge public interests⁵ and track disease outbreaks.⁶ Similar applications of this tool are observed in the ophthalmology literature; Google Trends has been used to detect conjunctivitis epidemics⁷ and evaluate public interest in cataract and refractive procedures.⁸

In this study, we sought to examine the influence of DTCA on internet-based information-seeking behavior pertaining to TED.

Methods

In this descriptive cross-sectional study, data that were downloaded from Google Trends on October 17, 2021, were used to characterize internet-searching behavior. The institutional review board of the University of California Los Angeles determined that this study was subject to exemption from institutional review board review. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines were followed.

Google Trends is a publicly available analytical tool that provides data on monthly search volume for specific terms across a specified time range and region. Search data were normalized and scaled from 0 to 100 to provide a relative search volume (RSV) for each topic.⁹

In this study, we queried Google Trends and downloaded monthly RSV data for the following terms: “thyroid eye disease,” “Tepezza,” and “teprotumumab.” Data were obtained for searches made within the US from January 1, 2004, to September 30, 2021 (Google Trends does not provide data before 2004). Results were scaled to the month of highest search volume for “thyroid eye disease” (December 2020). Trends in monthly RSV for each search term were examined graphically (Figure).

Figure. US Search Volumes for Thyroid Eye Disease (TED), Tepezza, and Teprotumumab From January 2004 to September 2021.

^aSeptember 2019: Horizon launches Facebook community web page “Listen to Your Eyes,” which provides public education on TED, as part of a digital marketing campaign.

^bJanuary 2020: The US Food and Drug Administration approves Tepezza (teprotumumab-trbw) for the treatment of TED.

^cDecember 2020: First unbranded TED awareness commercials are aired on national television, which include references to Horizon-sponsored websites on TED.

^dMay 2021: First brand-name commercial for Tepezza is aired on national television.

Statistical Analysis

Mean monthly RSV values and percent changes were determined for the specific time periods of interest (those preceding or associated with major events in the teprotumumab DTCA campaign). All analysis was performed using Microsoft Excel 2019 (Microsoft Corporation). Data are presented descriptively.

Results

From January 1, 2004, through June 30, 2019, searches for TED demonstrated a relatively stable baseline level, with a mean (SD) RSV of 1.78 (1.25) during that time period.

Searches for TED increased by 33% (3%-4%) from June 2019 to December 2019. After FDA approval of teprotumumab in January 2020, there was a further 25% increase (4%-5%) in searches over the previous month. A peak in search volume was noted from May 2020 to July 2020 that represented a 300% increase (4%-16%) in searches for TED. The largest peak was observed in December 2020, representing a 525% increase (16%-100%) from the previous month. TED search volumes decreased in the initial months of 2021, but subsequently rose by 640% (5%-37%) from April 2021 to May 2021, this time with a corresponding increase in searches for “Tepezza,” which increased by 600% (3%-21%) during the same period.

Discussion

The findings of this cross-sectional study suggest that public interest in TED, as measured by online search traffic, demonstrated substantial increases during several months in 2020 and 2021. Although these results cannot be used to derive direct causal inferences, there are some interesting patterns that emerge when TED search trends are juxtaposed against major events in the teprotumumab marketing campaign.

A modest increase in TED searches before FDA approval corresponds with the prelaunch TED awareness campaign led by Horizon Therapeutics.³ Interestingly, although an increase in TED searches was noted at the time of teprotumumab’s FDA approval in January 2020, the first major peak occurred several months later, in approximately May 2020. One possible explanation for a delayed online reaction to FDA approval is that public attention in the first quarter of 2020 may have been centered on the initial outbreak of the COVID-19 pandemic.¹⁰

Also noteworthy is that the highest peak in searches for TED, occurring in December 2020, coincided with Horizon’s first unbranded commercial run on national television.³ The advertisements featured animations of inflamed and painful eyes caused by TED and included references to Horizon-sponsored websites where viewers could go to learn more about TED and potential treatment options. Of the 1 million visits that were logged to these websites during the year of 2020, 60% occurred in December alone, after the launch of the national advertisements.³

The most recent spike in TED searches, occurring in May 2021, is particularly interesting given that it was associated with a similar increase in searches for the brand-name medication. A plausible explanation for this observed association is that May 3, 2021, marks the date that Horizon released its first brand-name commercial for teprotumumab on national television,¹¹ a notable change from previous advertisements that focused solely on TED signs and symptoms.

Our findings are comparable with previous studies that used Google Trends to examine searches for new medications. One such study found that searches increased for several antipsychotic medications after FDA approval, although the timing and magnitude of increase varied widely between medications.¹² A separate study found that DTCA was associated with an increase in searches for 2 drugs used to treat benign prostatic hyperplasia.¹³ These results are similar to our findings, which suggest that DTCA may have a greater influence on search traffic than FDA approval alone.

One notable difference between our study and prior investigations is that we examined searches for both the medication and the disease itself. Advertising campaigns have previously driven public interest in treatment of medical conditions; DTCA proponents assert that advertisements act as a disease awareness tool for the public.¹⁴ However, DTCA is controversial with regard to its net benefit on patient care. Potential harms include biased or misleading information, widening of disparities in health care literacy, and overtreatment, among others.¹⁴ Literature from DTCA-prevalent fields, such as oncology, offers insight on strategies for mitigating these potential harms.¹⁵ Emphasis is placed on providing patients with balanced information, including realistic expectations for success with the advertised drug and equal consideration of nonadvertised alternatives. Clinicians have also been advised to remain vigilant about monitoring and evaluating direct-to-consumer communication. A free and easily accessible tool such as Google Trends may prove useful for evaluating the influence of DTCA campaigns in real time.

Limitations

There are some limitations that must be considered when using Google Trends data as a research tool. As mentioned previously, causal inferences cannot be drawn from these data. Additionally, Google Trends data do not directly reflect public awareness of a subject. Instead, these data serve as a proxy for public awareness via relative search traffic, which might be better categorized as a measurement of public interest. Despite these limitations, however, Google Trends remains a powerful tool for examining public engagement with specific topics.

Conclusions

In this cross-sectional study, we used Google Trends to specifically examine the potential association of DTCA with public interest in TED. Our findings suggest that DTCA campaigns for teprotumumab may have been associated with an increase in internet search traffic for TED. However, additional studies on this topic are warranted, such as those that examine how DTCA may influence changes in referral patterns for conditions such as TED.