Introduction

At the very beginning of medical history, medicines were discovered from nature like plants and animals. In the Modern Age, however, medicines are born from the chemical process, including the utilization of pre-existing ones, also known as Drug Repurposing (DR). For instance, the Ebola treatment Remdesivir is used to treat severe COVID-19 patients (Beigel et al., 2020) and Aspirin, the painkiller, as heart disease treatment. Viagra (sildenafil), one of the primary money-makers of Pfizer is also one of these instances because it was originally designed for hypertension but widely prescribed as an erectile dysfunction drug. And recently, Viagra again sheds light on another medical field—Alzheimer’s Disease (AD). On December 6, 2021, researchers from Cleveland Clinic published to Nature Aging that Viagra might reduce the risk of AD by 69% (Cheng et al., 2021). BBC News on the same day highlights this research by titling “Viagra may be useful against Alzheimer's dementia” without bylines revealing the author (2021).

Purpose, Methodology, Methods, and Results

Fang, J., Zhang, P., Zhou, Y., Ching, C., Tan, J., Hou, Y., Stauffer, S., Li, L., Pieper, A., Cummings, J., & Cheng, F. (2021). Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease. Nature Aging, 1–14.

Alzheimer’s Disease (AD) is the most prevalent form of dementia, with patient counts of approximately 44 million across the world without a cure (Cheng et al., 2021; Alzheimer’s News Today, n.d.). Until now, the two hallmarks stimulating AD have been widely researched for more than 25 years, which are beta-amyloid and tau proteins, but approaches of discovering anti-amyloid or anti-tau selective drugs “have a lack of clinical benefits of patients with AD” (Cheng et al., 2021). Thus, the Cleveland Clinic research team decided to incorporate existing data resources that were not fully utilized to discover AD drugs to repurpose their pharmaceutical use.

First, the team compiled US Food and Drug Administration-approved 1,608 drugs that target both beta-amyloid and tau because the treatment should be affecting both hallmarks. Then, the researchers further narrowed it down to 66 candidates and identified sildenafil as the top candidate by analyzing clinical and preclinical evidence related to AD.

Next, the team conducted longitudinal research by examining the 7.23 million US insurance claims data spanning six years. First, they did a cohort study of comparing sildenafil users and non-sildenafil users, then conducted another cohort to compare sildenafil with four comparator drugs that were the treatments for hypertension (diltiazem, losartan) or diabetes (glimepiride, metformin), which also target both amyloid and tau proteins like sildenafil. For the first cohort, the team used the Cox regression analysis to compare matched non-sildenafil users to sildenafil users. The Cox regression is one of the survival analyses, which investigates the “effect of several variables upon the time a specified event takes to happen” (StatsDirect, n.d.). After examining the six years of follow-up, sildenafil usage was proved to be associated with the reduced risk of AD by 69%.

The latter cohort of comparing five drugs confirmed that sildenafil significantly decreases the AD risk than the other four comparator drugs (diltiazem, losartan, glimepiride, metformin) with propensity score-stratified analysis. A propensity analysis reduces selection bias and controls for the potential influence of confounding factors, thus frequently used to estimate relevant clinical effects adjusted for given confounders (Littnerova et al., 2013). Moreover, the Cleveland Clinic team further conducted subgroup analyses for age, sex, race, and disease comorbidities to make the “sildenafil users have equal health/disease conditions on average with those receiving comparator drugs” (Cheng et al., 2021).

This study holds significance since utilizing massive longitudinal data enables generalizing to the “real-world patient populations, while maintaining adequate statistical power” (Cheng et al., 2021). However, the incomplete data and possible selection bias have not been perfectly controlled, such as education level and socioeconomic status. Furthermore, sex-specific subgroup analyses showed the sildenafil usage’s decreasing risk of AD for men across all comparator drugs, whereas, for women, it was only for diltiazem. Lastly, the research is limited to investigating computational models; thus, it requires randomized clinical trials for future research.

Artifact Analysis

Main Points of the Artifact

The article from BBC News primarily concentrates on simply delivering the information since the study was considered groundbreaking. It starts with explaining what sildenafil means by referring to Viagra for the readers, then summarizes the major discoveries such as sildenafil users showing a reduced risk of AD compared to non-sildenafil users based on six years of US insurance claims data. The article then mentions the limitations of how the sildenafil usage only associates with reduced AD without establishing causality by citing the lead investigator Dr. Feixiong Cheng. Additionally, the BBC further implies skepticism towards the study by adding new possible limitations.

Evidence Given in Support of the Main Point

Although the article provides evidence for sildenafil reducing the risk of AD, it hints at the skepticism about the result. By citing scholars other than the Cleveland Clinic that conducted the research (University of Edinburgh, University of Tasmania), the BBC clarifies that sildenafil has not yet been fully studied, and most of the highly-anticipated treatments for AD have failed during clinical trials.

Author and Sponsor of the Artifact

The most notable aspect of the artifact is that nowhere in the article provides information about the author. The BBC never explicitly comments on the reason for the absence of bylines, but I can assume why through their post of “Learn how the BBC is working to strengthen trust and transparency in online news” (2017). It is because the newspaper focuses on the subject of journalism as an organization as a whole, according to their 2017 post. The post never mentions individual journalists, unike many other newspapers; for example, Sky News’ post about policies and standards underscores journalists’ duty to follow the legal and regulatory frameworks (2021). 

When looking at another no-author newspaper The Economist’s post in 2013 about their reason for removing bylines, it makes the assumption easier of why BBC lacks bylines. According to The Economist, not adding writers’ names provides journalists the “freedom to assume different voices,” which ultimately emphasizes that “what is written is more important than who writes it” (2013).

Both the BBC and The Economist’s validation may seem plausible, but there is room for opposition. For instance, the readers cannot judge whether the article is credible since it leaves the author’s name in the murky waters. This might indicate the degradation of BBC’s accountability, transparency, and impartiality (Metcalf-Fisher, 2021), which could arouse doubts for the overall articles, including this paper’s cited source related to the Cleveland Clinic’s empirical study.

The sponsor for the exact article could not be found, but the information of the top ten donors for the BBC was provided from its website. It included the UK Foreign and Commonwealth Office, the Swedish International Development Cooperation Agency (SIDA), the European Union, and more (2020).

Target Population

Since the BBC article for this paper focuses on delivering information rather than calling for action, defining a target population is challenging. But to assume from the last part of the article that mentions how the research is yet indefinite about the causality between sildenafil and AD, the article proposes that prejudging sildenafil as the cure might be a hasty expectation. Thus, the possible target population may be the family of AD patients looking for treatment.

Accuracy

Due to the limited word counts to effectively summarize the empirical study, the BBC article focused on the primary findings and limitations, sometimes lacking further explanation. Therefore, a few of the wordings need elaboration or clarification to prevent readers’ misinterpretation. For example, the article mentions that “[high] doses of [sildenafil]” reduced amyloid and tau proteins’ accumulation, which stands for the incidence of AD (2021). However, the research specifically points out that a higher average daily dosage of sildenafil is irrelevant to reduced AD. Of course, the term “high” in this article might not particularly refer to high “daily dosage” but may rather indicate the higher dosage compared to non-sildenafil users. Nevertheless, it is important to note this wording because readers may perceive that the more Viagra (sildenafil) they take, the less likely they are to be diagnosed with AD, which is wrong.

            Furthermore, the article lacks one of the major limitations of the research that it failed to confirm the association between sildenafil usage and females’ AD incidence. Since Viagra is mostly prescribed to males, the research holds limitations in terms of selection bias that can severely affect the clinical trial phase. This ultimately suggests that the research has yet to confirm the sildenafil’s effect for at least half of the population in the entire world, which the article should have addressed.

References

Alzheimer’s News Today. (n.d.). Alzheimer’s Disease Statistics. Retrieved from https://alzheimersnewstoday.com/alzheimers-disease-statistics/

Beigel, J. H., Tomashek, K. M., Dodd, L. E., Mehta, A. K., Zingman, B. S., Kalil, A. C., Hohmann, E., Chu, H. Y., Luetkemeyer, A., Kline, S., Lopez de Castilla, D., Finberg, R. W., Dierberg, K., Tapson, V., Hsieh, L., Patterson, T. F., Paredes, R., Sweeney, D. A., Short, W. R., … Lane, H. C. (2020). Remdesivir for the Treatment of Covid-19—Final Report. The New England Journal of Medicine. 383(19), 1813-1826.

Fang, J., Zhang, P., Zhou, Y., Ching, C., Tan, J., Hou, Y., Stauffer, S., Li, L., Pieper, A., Cummings, J., & Cheng, F. Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer’s disease. Nature Aging. 1-14.

Learn how the BBC is working to strengthen trust and transparency in online news. (2017, December 8). BBC News. https://www.bbc.com/news/help-41670342

Littnerova, S., Jarkovsky, J., Pavlik, T., Spinar, J., Dusek, L. (2013). Why to use propensity score in observational studies? Case study based on data from the Czechclinical database AHEAD 2006–09. Cor et Vasa, 55(4), e383-e390.

Metcalf-Fisher, M. (2021, January 19). Most major news websites give reporters byline, so why doesn’t BBC?. PR Week.

https://www.prweek.com/article/1704866/major-news-websites-give-reporters-byline-so-why-doesnt-bbc 

Sky News policies and standards. (2021, October 8). Sky News. https://news.sky.com/info/policies-and-standards 

StatsDirect (n.d.). Cox (Proportional Hazards) Regression. Retrieved from https://www.statsdirect.com/help/Default.htm#survival_analysis/cox_regression.htm.

Viagra may be useful against Alzheimer’s dementia. (2021, December 6). BBC News. https://www.bbc.com/news/health-59546948

Where our money comes from. (2021). BBC News. https://www.bbc.co.uk/mediaaction/about/funding 

Why are The Economist’s writers anonymous?. (2017, March 27). The Economist. https://medium.economist.com/why-are-the-economists-writers-anonymous-8f573745631d