Despite compelling data from trials like PATINA, some patients with ER+/HER2+ breast cancer refuse maintenance endocrine therapy due to side effects. This highlights a real-world gap between clinical trial evidence and patient adherence, forcing oncologists to navigate patient preferences against optimal treatment protocols.

The number of Americans recommended for statins ballooned from 13 million to 56 million due to progressively lowered cholesterol thresholds. The expert committees setting these guidelines often had members with financial ties to drug makers, creating a conflict of interest.

The FDA receives raw and cleaned datasets from sponsors, not just summary reports. Their internal teams conduct independent analyses, which can lead to findings or data presentations in the official drug label that differ from or expand upon what's in the published paper.

The enzalutamide arms saw discontinuation rates of 20-25% due to adverse events. This high rate reflects a different risk calculation for patients who feel healthy and are asymptomatic. Unlike in advanced disease where patients tolerate more toxicity, this population has a very low threshold for side effects, making early intervention a significant trade-off.

A critical distinction exists between a clinical adverse event (AE) and its impact on a patient's quality of life (QOL). For example, a drop in platelet count is a reportable AE, but the patient may be asymptomatic and feel fine. This highlights the need to look beyond toxicity tables to understand the true patient experience.

Taking a statin may create a false sense of security. One study, dubbed 'Gluttony in the Age of Statins,' found that over 10 years, statin users were more likely to gain weight and become sedentary, likely believing the pill negated the need for a healthy lifestyle.

The 'Number Needed to Treat' (NNT) for statins is around 100. This means 100 people must take the drug for five years for just one or two to avoid a heart attack. The vast majority (98%) derive no direct benefit, challenging the drug's 'miracle' status.

Despite showing massive weight loss, new obesity drugs from Eli Lilly and others have high discontinuation rates due to side effects. This suggests the industry's singular focus on efficacy may be hitting diminishing returns, opening a new competitive front based on better patient tolerance and adherence.

The silent nature of high cholesterol creates a psychological barrier. Patients who feel perfectly healthy are often unwilling to commit to lifelong treatment, even when their risk is high, leading to preventable cardiovascular events.