Surrogate outcomes, progression-free survival: important issues for journalists & consumers to grasp

In a BMJ analysis published this week (unfortunately, a subscription is required for full access), Mayo’s Dr. Victor Montori and two co-authors wrote that the use of surrogate outcomes to suggest a benefit from medical interventions – instead of “important patient outcomes such as death, quality of life or functional capacity” – was damaging patient care.

Excerpts:

Diabetes care is largely driven by surrogates. …Much of the evidence for clinical interventions is based on their effect on surrogate outcomes rather than those that matter to patients such as quality of life or avoidance of vision loss or renal failure. Moreover, because these “hard” end points generally show much smaller responses to interventions than surrogate markers, many of the widely accepted strategies for diabetes may be based on artificially inflated expectations.

…

Not only are markers given more importance than is justified by the evidence but they also begin to take on an existence of their own as new disease entities. And despite being far from perfect surrogates for outcomes, glucose, lipid, and blood pressure thresholds are used to evaluate quality of healthcare and to influence reimbursements. So clinicians spend time exploring ways of reducing the level of the surrogate, even when the only options are interventions that do not improve, or may even worsen, a patient’s outlook.

…

The growing trend has been for the focus on surrogates to dominate both research and clinical agendas on non-communicable diseases, with the connivance of public health, professional societies, and drug companies. We argue that the disconnect between surrogate and hard outcomes in terms of degree of benefit or harm, or even its direction, makes it important to review this. Changes are needed in both current criteria for registration of new drugs targeted at reducing risk of complications and current formulas for measuring quality and reimbursing doctors.

These are very important issues for journalists to understand and to report on.

And it’s important for consumers to understand that not all claims they hear about supposed benefits of medical interventions have been proven to impact things that really matter in peoples’ lives.

It’s interesting that just yesterday we commented on 7 stories reporting on the drug Avastin for ovarian cancer – some calling the study results disappointing, others reporting it as real progress.  The difference hinged on one’s view of progression-free survival as a meaningful outcome.

Such issues are going to be increasingly more important – and our understanding of the underlying evidence will be even more important as we try to grasp which research results really matter.