Patient Life-Years Lost to Long Approval Times

A high number of patient life-years are lost to regulatory delays for drug approvals, according to an analysis presented at the 2015 World Conference on Lung Cancer in Denver, Colorado (abstract 22.05).

“Survival of incurable cancer patients is improving gradually,” said lead study author David Stewart, MD, head of the division of medical oncology at the University of Ottawa in Ontario, Canada. “Several hundred new therapies are under development. However, internationally, regulatory complexity slows progress by increasing drug development costs.”

In the 1960s, the average time from drug discovery to marketing was 8 years, compared with 13.9 years since 2000, he noted.

To attempt to quantify the human impact of regulatory delays, Stewart and his coauthors analyzed survival benefits and approval times for 21 therapies studied for 10 types of cancer that had undergone phase III clinical trials between 2001 and 2015. The list included four studies of non–small-cell lung cancer (NSCLC) treatment, with erlotinib, bevacizumab, cetuximab, and nivolumab. They calculated the life-years lost per year of approval delay by multiplying the number of deaths per year for the specific patient subgroups included in the clinical trials by the median survival gain. The team also calculated life-years lost between drug discovery and approval in the United States; life-years that would be saved if time from discovery to approval for these agents was reduced to 5 years or less; and life-years saved by improved trial safety, Stewart said. 

“When the combined impact of all tumor sites and drugs are considered together, there were 29 life-years lost in North America per day of delay in therapy approval-one for every 2 minutes of delay,” he reported. “A huge number of life-years are being unnecessarily lost.”

Those figures do not take into account the impact of drugs non-evaluable due to crossover or missing survival data, drugs that were prematurely abandoned, or drugs that are still undergoing investigation, he added.

“Clearly, the survival gains associated with the foregoing drugs are only modest,” he said. “However, there would be a large negative impact associated with approval delays even if factors such as comorbidities, performance status, ability to pay, etc. limit the number of patients treated to a fraction of the total dying from a specific malignancy.”

The life-years lost to delayed therapy approvals dwarf those saved through increased safety resulting from enhanced regulations, Stewart believes, based on extrapolations from toxic deaths reported on phase I trials.

Accelerated regulatory-approval processes now allow some approvals based on phase I/II data, Stewart acknowledged. “Accelerated approval and breakthrough drug designations help, but they primarily just remove the long final phase III component. It does not address the rapidly growing regulatory hurdles that squander lives by preventing approval from being even faster.”