ideasIdea
Time to treatment failure and quality of life as co-primary endpoints in non-curative trials
For treatments that will not cure, what matters is how long the treatment keeps working without becoming unbearable, and how the person feels. Trials should measure both of those as their main results.
In palliative-intent settings, trials adopt time to treatment failure (progression, death or discontinuation for toxicity or patient choice) together with a validated QoL instrument (EORTC QLQ-C30 or disease module) analysed as time to definitive deterioration, as co-primary endpoints, with OS as a key secondary. PFS alone rewards drugs that delay scan progression while making patients feel worse.
Hypothesis
Trials with TTF plus QoL co-primaries will more often identify regimens that patients continue and prefer, and drugs approved on these endpoints will show better real-world persistence than drugs approved on PFS alone.
Rationale
Discontinuation for toxicity is common with modern combinations and invisible in PFS. Regulators have accepted QoL-based labels in some settings; the co-primary structure protects against approving effective-but-intolerable regimens.
What would test it
Re-analyse completed phase 3 trials with available PRO data under the co-primary framework and identify decisions that would have changed; then run a prospective trial in a common palliative setting with the new endpoints.
Maturity
speculative
Who has to act
regulator
Cost to try
Small (under $1M)
Years to first evidence
3
Bottlenecks it attacks
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
- Toxicity and quality of life are undervalued · Trials measure how long people live, not how they live. Side-effects are under-reported and under-treated.
- Patients lack understanding, navigation and agency · Most patients cannot understand their options, find trials, or push back, so decisions are made for them.