Life Wellbeing Poorly designed cancer drug trials may be exaggerating benefits

Poorly designed cancer drug trials may be exaggerating benefits

Many cancer trials that supported new drug approvals were found to be at high risk of bias. Photo: Getty
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The “breakthrough” cancer drugs that are frequently heralded in media reports are not delivering in terms of patient survival rates – and most are not even designed with life extension as the prime measure of success.

Deficits in the design, conduct and analysis of clinical trials – and in some jurisdictions, a culture of rushed approvals – are to blame.

Some of this “might be unavoidable because of the complexity of cancer trials,” UK researchers have concluded, following a devastating review of clinical trials that led to new cancer drug approvals in Europe between 2014 and 2016.

Wonder drugs not so wonderful?

Half of them were “were judged to be at high risk of bias”, which suggests that the efficacy of these drugs may have been exaggerated.

The findings add weight to existing research that raises serious concerns about low standards of evidence supporting new cancer drugs.

Australian researchers – Barbara Mintzes is an associate professor at the School of Pharmacy, University of Sydney and Agnes Vitry from University of South Australia – have responded to the new paper with an editorial that calls on researchers to “raise the bar” to ensure real benefits to patients.

Both the paper and the editorial were published this week in the British Medical Journal.

The cost of faster approvals

They write: “The aim of faster approvals is to get potentially life-saving care to patients as soon as possible, especially those with rare cancers or life-threatening diseases whose conditions do not respond to existing treatments. However, faster approval comes at a high cost.”

Several studies have shown the evidence of patient benefit that underpins approval “is limited and uncertain”.

The authors note that overall survival was evaluated as “a primary endpoint” in only 26 per cent of trials of new cancer drugs and indications approved in Europe from 2009 to 2013.

The remaining approvals were based on surrogate measures such as progression-free survival or response rate, which have a low or modest correlation with overall survival.

Cancer drugs with accelerated approvals in the United States from 1992 to 2017 delivered a “survival advantage” for only one in five patients.

Barely a third (32 per cent) of cancer drugs approved by the US Food and Drug Administration and the European Medicines Agency from 2003 to 2013 “had clinical trial evidence of improved quality of life”.

How does this translate to the Australian scene?

On the one hand, as Dr Vitry told The New Daily, clinical trials have an international currency.

When the Australia Therapeutic Goods Administration approves a new drug, it takes into account whether it’s been approved in other jurisdictions, such as Europe and the US.

On the other hand, as Dr Vitry and Dr Mintzes write: “In Australia the Pharmaceutical Benefits Advisory Committee, which makes national funding recommendations, frequently rejects cancer medicines because of uncertain clinical evidence.”

However, a 2017 review found that more than half of new cancer drugs were rejected by the funding body, with the most frequent reasons for rejection offered by the PBAC was “inadequate cost-effectiveness or drug price too high”.

Whatever the case, the efficacy of new cancer drugs is largely unspectacular.

Trials not only flawed, but potentially hazardous

In 2015, US and Canadian researchers published a paper – “Why do cancer drugs get such an easy ride?” – that detailed the paltry gains made by many new drugs in terms of patient survival: “The 71 drugs approved by the FDA from 2002 to 2014 for solid tumours resulted in median gains in progression-free and overall survival of only 2.5 and 2.1 months, respectively.”

Dr Vitry and Dr Mintzes offer this warning: “Uncertainty and exaggeration of the evidence that supports approval of cancer drugs causes direct harm if patients risk severe or fatal adverse effects without likely benefit, or forgo more effective and safer treatments.

“Inaccurate evidence also leads to intangible harms if it encourages false hope and creates a distraction from needed palliative care.”

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