Surrogate Endpoints in Clinical Research. Clinical Trials

1
SURROGATE ENDPOINTS

• PRESENTED BY - DIGVIJAY Patil, MAYURI Bhome

2
Layout

• Introduction
• Types of clinical endpoints
• Surrogate endpoints
• Importance of surrogate endpoints
• Benefits for surrogate endpoints
• Advantages of surrogate endpoints
• Disadvantage of surrogate endpoints
• References

3
Introduction

• What are clinical trial endpoints?
• A clinical trials endpoints measure the outcomes
  in the trial. When a trial evaluates the efficacy
  of a new medical product or a new use for an
  approved product, investigators may choose
  endpoints that directly measure the clinical
  outcome they want to study.

4
Types Of Endpoints

• Clinical Endpoint
• Surrogate Endpoint
• Biomarker Endpoint
• True Endpoint

5
Surrogate Endpoint(1/3)

• Surrogate endpoints be used instead of clinical
  outcomes in some clinical trials.
• A surrogate endpoint is a physical measurement
  of a specific outcome which is considered to be a
  valid predictor (or representative) of the real
  outcome or final result.
• Surrogate endpoints are used when the clinical
  outcomes, like strokes, might take a very long
  time to study, or in cases where the clinical
  benefit of improving the surrogate endpoint, such
  as controlling BP, is well understood.

6
Surrogate endpoint (2/3)
Intervention
Surrogate endpoint
Clinical hard endpoint
Disease
Time
7
Surrogate Endpoints (3/3)

• Surrogate endpoint is like a measurable indicator
  that can help us know what the real result 
• Before a surrogate endpoint can be accepted in
  place of a clinical outcome, extensive evidence
  must accumulate, including evidence from
  epidemiological studies and clinical trials.
• Usually clinical trials are needed to show that
  the surrogate endpoint can be relied upon to
  predict, or correlate with, clinical benefit in a
  context of use

8
Importance of Surrogate Endpoints

• When a surrogate endpoint clearly predicts a
  beneficial effect through appropriate studies,
  its use generally allows for more efficient drug
  development programs.
• Many clinical trials, using a range of different
  blood pressure lowering medications, have
  demonstrated that reducing systolic blood
  pressure reduced the risk of stroke.
• Measurement of reduction in the surrogate
  endpoint of systolic blood pressure can stand in
  for the clinical outcome of stroke, and clinical
  trials targeting the reduction of risk of stroke
  can be conducted more rapidly in smaller
  populations using this validated surrogate
  endpoint.

9
Advantage Of Surrogate Endpoints (1/2)

• Using surrogate outcomes reduces costs for
  manufacturers since it reduces the duration of
  the clinical trial which means the new
  intervention could be introduced to the market
  faster.
•  Surrogate endpoints on some occasions, be useful
  since they could give more balanced findings than
  using real outcomes. 
• They may be used instead of stronger indicators,
  such as longer survival or improved quality of
  life, because the results of the trial can be
  measured sooner.

10
Advantage Of Surrogate Endpoints (1/2)

• The assessment of "hard" primary clinical
  endpoints (such as death and heart attack) often
  requires large long-term clinical trials which
  can be quite expensive.
• The use of surrogate endpoints can allow trials
  to evaluate the efficacy of a new drug or device
  more rapidly, more efficiently and more
  inexpensively.

11
Disadvantages of surrogate endpoints (1/2)

• The surrogate endpoint may intuitively be
  hypothesized to be related to a "hard endpoint"
  such as death or heart attack, but may not be.
• While a surrogate endpoint may be related to a
  "hard endpoint" such as death or heart attack, it
  is not clear that a reduction in the surrogate
  endpoint will lead to an improvement in the "hard
  endpoint" in death or heart attack.
• While a surrogate endpoint may be related to a
  "hard endpoint, it may be an causual association
  (the surrogate may not lie in the causal pathway
  to the "hard endpoint" and changing the surrogate
  endpoint may not change the "hard endpoint"

12
Disadvantages of surrogate endpoints (2/2)

• The agent may reduce the surrogate endpoint, but
  due to off target toxicity, may increase the
  risk of "hard endpoints" such as death or MI.
• The relationship between the surrogate endpoint
  and the "hard endpoint" may be non-linear or may
  be a threshold effect.
• There have been a number of instances when
  studies using surrogate markers have been used to
  show benefit from a particular treatment, but
  later, a repeat study looking at endpoints has
  not shown a benefit, or even a harm.

13
References

• https//www.fda.gov/drugs/development-resources/su
  rrogate-endpoint-resources-drug-and-biologicdevelo
  pmenttextA20surrogate20endpoint20is20a,to
  20predict20that20clinical20benefit
• https//www.wikidoc.org/index.php/Surrogate_endpoi
  nttextThe20use20of20a20surrogate,of20imp
  rovements20in20clinical20outcomes
• https//www.ncbi.nlm.nih.gov/pmc/articles/PMC18848
  46/

14
THANK YOU !!