Different types of endpoint in clinical research

1. ENDPOINTS IN CLINICAL
RESEARCH
BY:
DEEPAK SHARMA
NATIONAL INSTITUTE OF PHARMACEUTICAL
EDUCATION AND RESEARCH, MOHALI

2. Table of Content
• Introduction
• Definition
• Classification of endpoint
• Other type of endpoint
• Endpoint in oncology
• Reference

3. Introduction
• In a clinical research trial, endpoint generally
refers to objective of a study or trial.
• The primary endpoint of a clinical trial is the
endpoint for which subjects are randomized
and for which the trial is powered. Secondary
endpoints are endpoints that are analyzed for
which the trial may not be powered.

4. Definition
• In clinical studies, end point is the final
outcome, the researcher needs to measure
while analyzing the overall efficacy or safety of
a drug.
• The variable capable of providing the most
clinically relevant and convincing evidence
related to the primary objective of the trial.

5. Classification of endpoint
Types of endpoint-
1. Primary vs. secondary endpoints
2. Hard vs. soft endpoints
3. Composite endpoint
4. Direct vs. surrogate endpoints

6. Primary endpoint
• Primary endpoint measure outcomes that will
answer the primary (or most important)
question being asked by a trial, such as
whether a new treatment is better at
preventing disease-related death than the
standard therapy.
• Example- fall in LDL level in cardiovascular
disease

7. Secondary endpoint
• Secondary endpoints that are analyzed post
hoc for which the trial may not be powered
nor randomized.
• Example-Mortality study following MI,
Incidence of cause-specific deaths, non-fatal
events/ hospitalizations.

8. Hard endpoint
• It is measured by observation.
• It is quantitative in nature.
• For example- Cardiovascular studies, death or
MI.

9. Soft endpoint
• It is often qualitative in nature.
• It is more subjective.
• For example- reduction in morning stiffness is
a soft endpoint. It is equally important in the
final assessment of the therapeutic
effectiveness/ safety.

10. Composite endpoint
• A combined or composite endpoint in a
clinical trial is a clinically relevant endpoint
that is constructed from combinations of
other clinically relevant endpoints.
• If a single primary endpoint is not suitable and
cannot be selected from multiple
measurements associated with the primary
objective, then another strategy is to combine
several measures.

11. Surrogate endpoint
• The National Institutes of Health (USA) defines
surrogate endpoint as "a biomarker intended
to substitute for a clinical endpoint".
• In clinical research trials, a surrogate endpoint
is a measure of effect of a specific treatment
that may correlate with a real clinical
endpoint but does not necessarily have a
guaranteed relationship.

12. Other type of endpoint
1. Clinical endpoint
2. Mortality
3. Intermediate and final outcomes
4. Patient reported outcomes
5. Morbidity health-related quality of life

13. Clinical endpoint
• In a clinical research trial, a clinical
endpoint generally refers to occurrence of
a disease, symptom, sign or laboratory
abnormality that constitutes one of the target
outcomes of the trial.

14. Mortality
• It is important to note that endpoints may
include adverse reactions that reflect on the
safety of the treatment.
• Adverse reactions are often collected as
secondary endpoints and there is likely to be
variation across studies in how adverse events
are reported in terms of both detail and
terminology.

15. Intermediate and final endpoints
• An intermediate endpoint is a clinical
endpoint associated with the use of a
pharmaceutical such as measure of a function
or of symptoms (disease-free survival, angina
frequency.
• It is not the ultimate endpoint of the disease,
such as survival or the rate of irreversible
morbid events

16. Patient reported outcomes
• A patient reported outcome (PRO) is a health
outcome directly reported by the patient who
experienced it.
• It specifically refers to "self-reporting" by the
patient.

17. Morbidity health-related quality of
life
• Quality of life measures constitute clinical
endpoints.
• HRQOL measures result from assessment of
multiple dimensions related to patients’
disease and its treatment, they may be
susceptible to changes due to a variety of
external factors.

18. Endpoints in oncology
1.Overall survival
It is the time from randomisation to until
death from any cause of patient.
2. Progression free survival
It is the time from randomization to until
disease progression or death of the patient.

19. Reference
1. Chin R, Lee BY. Economics and patient
reported outcomes, Principles and practice of
clinical trial medicine. London, Amsterdam,
Burlington, San Diego: Elsevier Inc;
2008:145–166.
2. Kleist P. Composite Endpoints for Clinical
Trials: Current Perspectives. International
Journal of Pharmaceutical Medicine. 2006;
21(3):25-30.

20. Contd.
3. Rauch G, Beyersmann J. Planning and
evaluating clinical trials with composite
time‐to‐first‐event endpoints in a competing
risk framework. Statistics in medicine. 2013;
32(21):3595-3608.
4. Fleming TR, DeMets DL. Surrogate end points
in clinical trials: are we being misled?. Annals
of internal medicine. 1996; 125(7):605-613.

21. Contd.
5. Marquis P, Caron M, Emery M-P, Scott JA,
Arnould B, Acquadro C. The role of health-related
quality of life data in the drug approval processes
in the US and Europe. Pharmaceutical Medicine.
2011;25(3):147-160.
6. Bottomley A, Aaronson NK. International
perspective on health-related quality-of-life
research in cancer clinical trials: the European
Organisation for Research and Treatment of
Cancer experience. Journal of Clinical Oncology.
2007; 25(32):5082-5086.

22. Thank you