Issue 3 / 3 February 2014

WHO guards the guardians? It’s a question that applies to any organisation or group of people charged with monitoring the behaviour of others, whether it’s the police force or pharmaceutical regulatory authorities.

A number of researchers have recently turned their attention to a bit of guardian guarding, analysing drug approvals in an attempt to determine just how much doctors and patients can rely on the decisions of agencies such as the influential US Food and Drug Administration (FDA).

It’s always going to be a fine balancing act for the regulators.

Obviously they are responsible for ensuring new treatments are safe and effective but, at the same time, they don’t want to stifle innovation or needlessly delay bringing a potentially life-saving new drug to market.

A study published in the JAMA illustrates how difficult this balancing act can be — and how hard it can be for clinicians to interpret the regulators’ decisions and their possible implications for practice.

Researchers from the Yale University School of Medicine examined FDA documentation for the 188 novel therapeutic agents (new molecular entities or biological drugs) approved by the agency between 2005 and 2012 (for a total of 206 indications).

They found the quality of evidence varied widely.

Although FDA guidance documents suggest manufacturers should submit at least two trials, 37% of all indications were approved on the basis of a single pivotal trial.

For 45% of indications, approval was based entirely on trials with surrogate measures as their primary outcome (measuring, for example, a drop in blood pressure rather than an actual clinical result such as a reduction in stroke or mortality).

Comparative effectiveness information was available for less than half of the indications, meaning there was no way for clinicians to know whether the new drug was any better than treatments already available on the market.

To some extent, the sketchiness of the information is understandable. Most of the cancer drugs were approved on the basis of a single trial, for example, and the researchers suggested such regulatory flexibility “may well be warranted given the limited number of effective therapies and the poor prognosis associated with cancer”.

But, while treatments for life-threatening illness may need to be fast-tracked through the regulatory process, this does raise questions about the transparency of the process and the usefulness of information provided to doctors and patients.

One solution suggested by these authors would be for regulators to provide an outline of the quality of the evidence considered for each approval, perhaps even giving it a grade.

That way, doctors and patients would be better able to determine which treatments had a sound basis in evidence and which were really more experimental in nature.

It would also be good to see a consistent and rigorous approach to monitoring drugs after they are released on the market, something regulators around the world have long failed to achieve.

A report commissioned by the FDA last year found the agency’s “approach to drug oversight in the postmarket setting is not sufficiently systematic and does not ensure that it assesses the benefits and risks of drugs consistently over the drug’s life cycle”.

If the guardians could find a way to overcome that system failure, they would really be doing their job.

Jane McCredie is a Sydney-based science and medicine writer.

One thought on “Jane McCredie: Who’s on guard?

  1. Steve Hambleton says:

    In Australia our regulators (TGA and PBAC) do provide an outline the reasons that they approve or reject medicines for registration and subsidy.  The public reports do give some idea about the quality of the evidence considered for each approval and if prescribers wish they can read all of this background material.  TGA publishes the AuSPAR (Australian Public Assessment Record). The AusPAR provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine.  The PBAC similarly publishes a list of outcomes of its meetings with reasons for approval or otherwise together with the evidence that was relied upon to make those decisions.

    AMA remains confident that our processes are appropriate and transparent  to the sponsors, practitioners and patients and do assist prescribers when we are choosing therapeutic products for our patients.   Steve Hambleton


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