In clinical trials, both dose escalation and dose expansion have different roles but are with respect to the same backbone. Dose escalation seeks to identify the maximum tolerated dose (MTD) of a drug by increasing the dose given to patients in steps. Typically there are only a handful of participants on each dose level, usually 3-6 people. The drug dose will be modified according to the toxicity grade using internationally recognized crite-ria such as the Common Terminology Criteria for Adverse Events (CTCAE), so that safety may be maintained during the trial. This is the approach that will insure we find the safest and most effective dosing for subsequent study.
Dose expansion follows determination of MTD or recommended phase 2 dose (RP2D) For phase three, hundreds of patients participate to collect more data on safety and efficacy in a larger population. Larger sample size- gives us better insight on how different patient populations respond to the drug such as by age, sex or comorbidities This study found that dose expansion occurs infrequently (according to a one analysis specification this was rare), but it is beneficial in corroborating specific population dosing guidance — e.g., patients with renal impairments and or geriatric populations where drug metabolism dynamic operates differently; The Lancet Oncology 2021).
Cost and time: Different cost and timelines in dose expansion both in escalation phase. Dose escalation is typically spaced over 6 to 12 months, dependent on the complexity of the study and amount of dose levels tested. Although the budgeted amount for this phase may differ, a report from the Pharmaceutical Research and Manufacturers of America (PhRMA) states that early-phase trials, including dose escalation, can cost between $1 to $5 million. On the other hand, dose expansion costs can easily exceed $10 million for scheduling more participants and time to do so (one year is being conservative since these studies are likely to be in the field doing good clinical work 12-to-24 months or longer).
Pembrolizumab (Keytruda) provides a nice example of dose escalation and expansion. In their early trials, dose escalation was performed to define MTD. Subsequently, dose expansion was performed in over 500 patients to validate efficacy in various cancer types. This was widely credited with expediting the drug's approval for melanoma treatment, as later reported by The New England Journal of Medicine.
There is also the quote |"Understanding both the safety and efficacy across diverse populations is critical for drug approval and eventual clinical use":[drjanetwoodcock.wordpress.com] This understanding is a well appreciated expression of both dose escalation and dose expansion that are essential information for regulators and healthcare providers.
More on these two stages for study [here] (dose escalation vs dose expansion)