Heartbroken? Study raises concerns over certainty of efficacy based on biomarkers

A study from researchers at Yale School of Medicine, evaluating cardiovascular trials with primary surrogate endpoints from the past 20 years, have found a disconnect between these trials and clinical outcomes.

Recently published in the Journal of the American Heart Association (JAHA), the study was aimed at reviewing previously published trials to characterise the success of them meeting endpoints. Additionally, the researchers looked at follow up clinical outcome trials to determine if the surrogate and clinical outcome trials corresponded in relation to efficacy.

They identified a total of 220 published surrogate endpoint trials, of which 157 achieved primary endpoint objectives. Only 59 of these trials were followed up with a subsequent clinical outcome trial and of these just 24 validated the positive biomarkers. These findings were consistent with those from a sample cohort of nearly 400 screened articles that included 37 surrogate endpoint trials from six high-impact journals.

In the discussion, the team highlight that although the initial purpose of a surrogate endpoint is to predict benefits for patients the results from their work question the validity of this premise. This should be raised as a point of concern for investigators and policymakers, according to the researchers, as efficacy cannot be assumed with certainty based on a surrogate endpoint study alone. In an article from YaleNews the lead author Dr Behnood Bikdeli noted that even though these findings apply to the field of cardiovascular medicine only, doctors and researchers from other medical fields should have similar reservations about approvals of new therapies using biomarkers.