Inconsistent Clinical Trial Reporting of Adverse Effects Harms Patient Outcomes

Clinical trials are designed to evaluate the effectiveness of cancer therapies, but they come with a cost: Adverse effects (AEs). Such effects are largely under-reported, according to an article by authors led by David C. Calverley, MD, of Portland VA Medical Center in Oregon, published in the Journal of Clinical Oncology (JCO).

Cardiovascular problems, especially those involving blood clots, are a major concern for people undergoing cancer treatment. These include types of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), and arterial thromboembolism (ATE), such as heart attacks, strokes, and blood clots. These events increase hospital admissions and can delay or interrupt cancer therapy, leading to poorer outcomes and increased death rates.

Under-reporting or Misreporting Is Common

Reporting these AEs is challenging because there are different ways to measure AEs. Moreover, clinicians may not recognize when symptoms are treatment-related, especially in cases where patients are taking multiple medications or have comorbidities. Clinicians may attribute symptoms such as nausea and fatigue to the underlying condition rather than the therapy. Some clinicians report VTE using the Common Terminology Criteria for Adverse Events (CTCAE), although physicians vary in their VTE reporting.

Clinical trials set thresholds, grade 3 and higher, for AE reporting; mild or moderate events may not be included. Patients may be underreporting AEs, too. The authors of the article published in JCO analyzed Surveillance, Epidemiology, and End Results (SEER) data from the National Cancer Institute (NCI) for cause of death in patients from 1973 to 2012. The data showed that patients from the ages of 25 to 44 years experienced thromboembolism and infections as the most common causes of non-cancer death.

In addition, it is important to note that VTEs in clinical trials tend to occur more frequently in the first few months of a cancer diagnosis and decrease as time goes on. Patients often take part in clinical trials as the third or fourth line of treatment, which lessens the likelihood of thromboembolic events.

Prevention is Possible

The good news: VTEs and ATEs are preventable. In a large randomized controlled trial, primary thromboprophylaxis with 10 mg once-daily rivaroxaban anticoagulation reduced the risk for VTE or VTE-related death by 60%. (HR, 0.62 [95% CI: 0.39 to 0.99]) as compared with placebo. The trial enrolled patients who were at high risk for VTEs.

Another type of VTE reporting is central venous catheter (CVC)-related thrombosis, which is asymptomatic in 14% to 18% of patients but presents with serious symptoms in approximately 5% of patients. This is a somewhat common complication among patients with cancer. Guidelines from the American College of Chest Physicians (CHEST), the American Society of Clinical Oncology (ASCO), and others recommend that patients receive anticoagulation for at least three months and for as long as CVC persists.

Going forward, standardization of reporting of AEs from both clinicians and patients, as well as using prevention strategies such as blood thinners like rivaroxaban, may help reduce the number of AEs.