Surrogate Endpoints

What is a surrogate endpoint in clinical trials?

• A direct measure of patient satisfaction

• A substitute measure of expected clinical outcome

• A backup treatment plan when the primary therapy fails

• A placebo-controlled variable

Answer explanation

A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit.

FDA, 2025

What is the main reason surrogate endpoints are used in oncology trials?

• They guarantee long-term survival

• They are easier to explain to patients

• They reduce trial and allow earlier drug access

• They improve regulatory oversight

Answer explanation

Surrogate endpoints are used in drug development process because they are

○ Less costly

○ Require shorter follow-up time compared to a final clinical outcome

Which of the following is a true clinical endpoint?

• Objective Response Rate (ORR)

• Pathological Complete Response (pCR)

• Overall Survival (OS)

• Progression-Free Survival (PFS)

Answer explanation

1. A “true” clinical endpoint is a direct measure of how a patient feels, functions, or survives.

3. It reflects a tangible, meaningful health outcome rather than a proxy or surrogate.

2. Why Overall Survival (OS) is the gold standard:

• Measures time from treatment start until death from any cause

What is Progression-Free Survival?

• 
  Time until tumor grows or new lesions appear

• 
  No residual invasive cancer found in tissue

• 
  % of patients with tumor shrinkage (partial or complete response

Answer explanation

1. PFS – Progression-Free Survival

• Definition: The length of time during and after treatment that a patient lives without the cancer growing or spreading.

2. Response Rate (RR)

• Definition: The proportion of patients whose tumors shrink (partial response) or disappear (complete response) after treatment.

• Types:

  • Overall Response Rate (ORR) = complete + partial responses.

3.  PCRT – Pathologic Complete Response (pCR or pCR rate)

• Definition: No evidence of cancer in tissue samples taken after neoadjuvant treatment (e.g., chemo before surgery), especially in breast or rectal cancer.

• Measured in: Surgical specimens.

What kind of FDA approval is typically granted based on a surrogate endpoint?

• Accelerated approval

•  Emergency use authorization

• Full approval 

• No approval

Answer explanation

Accelerated Approval Program is FDA instituted to allow for earlier approval of drugs that treat serious conditions, and fill an unmet medical need based on a surrogate endpoint

FDA, 2025

What are common criticisms of surrogate endpoints in oncology? (Select all that apply)

• Predictive validity across disease contexts

• Regulatory pathway misuse and premature approvals

• Weak correlation with patient-centered outcomes

• Patient and physician misunderstanding of clinical significance

• All of the above

Answer explanation

• A. Predictive validity across disease contexts

• B. Weak correlation with patient-centered outcomes

• C. Regulatory pathway misuse and premature approvals

• D. Patient and physician misunderstanding of clinical significance

Are surrogate endpoints a necessary compromise for timely patient access, or not?