Concept of clinical trials

Overview

Clinical trials evaluate new cancer treatments through a staged process (Phase I-IV), each answering a distinct question before a treatment reaches routine practice
Most novel cancer therapies fail somewhere in this pipeline - the staged design exists specifically to identify unsafe or ineffective treatments before large-scale/routine use

Phase	Purpose	Typical size
I	Safety, dose-finding (maximum tolerated dose), pharmacokinetics	Small (10s)
II	Preliminary efficacy signal, further safety data	Moderate (10s-100s)
III	Definitive efficacy vs standard of care, usually randomised	Large (100s-1000s)
IV	Post-marketing surveillance - rare/long-term adverse effects, real-world effectiveness	Large, post-approval

Randomisation minimises selection bias/confounding, allowing observed differences to be attributed to the treatment rather than baseline group differences
Blinding (where feasible) reduces performance and assessment bias - often not fully possible in cancer trials with distinct toxicity profiles or surgical vs non-surgical arms
Intention-to-treat analysis (analysing patients according to their assigned group regardless of whether they completed treatment) preserves the benefit of randomisation and is generally preferred over per-protocol analysis for the primary efficacy outcome

Trial endpoints matter clinically: overall survival is the gold-standard endpoint but requires long follow-up; progression-free survival and response rate are faster surrogate endpoints, used more often in earlier-phase trials, but do not always translate into a survival or quality-of-life benefit
Discussing trial participation (where available and appropriate) is part of informed oncology care - trial access can offer earlier access to promising therapies alongside close monitoring

Evidence-based medicine hierarchy, informed consent, surrogate vs hard clinical endpoints

A positive Phase II result does not guarantee Phase III success - many promising early-phase signals fail to replicate in larger, randomised, controlled comparison, which is why Phase III remains the threshold for changing standard practice

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