Meaningful Endpoints

Choosing and Specifying End Points and Outcomes

Section 2

Meaningful Endpoints

Contributors

Lesley Curtis, PhD

Adrian F. Hernandez, MD, MHS

Kevin P. Weinfurt, PhD

 

 

Contributing Editor

Karen Staman, MS

A distinguishing feature of PCTs is a focus on outcomes that are “directly relevant to participants, funders, communities, and healthcare practitioners (Califf and Sugarman 2015).” A key question when considering endpoints and outcomes is: Who will use the information the most? Does the outcome matter to them? For example, researchers and regulators might be interested in measuring how an intervention reduces the risk of cardiovascular death. However, a patient does not care how the intervention reduces the risk of cardiovascular death if the overall risk of death is unchanged. Complicating matters, health care system leaders might care about broader endpoints (such as reduced infection rate), because these endpoints may affect the health system as a whole.

According to the PRECIS-2 (Pragmatic Explanatory Continuum Indicator Summary 2) criteria, “as the primary outcome becomes less recognizably important to patients, or is assessed on criteria seldom used in usual care, the trial becomes more explanatory [and less pragmatic] (Loudon et al. 2015).” Authors of the PRECIS-2 criteria provide an example of number of falls in elderly in the community as a pragmatic outcome, in contrast with surrogate endpoints such as bone density, muscle strength, and functional ability, when assessing an intervention designed to reduce falls. (Learn more about the PRECIS-2 tool.)

Qualities that make outcomes less pragmatic

  • Choosing a surrogate outcome or physiological outcome that is mainly important to providers (such as a blood test)
  • Using a composite outcome that is less important to patients
  • Choosing tests not normally used in usual care or outcomes that require central adjudication
  • Measuring a shorter-term outcome of an intervention for a condition in which patients are more concerned about longer-term outcomes

Note that use of a surrogate endpoint, while technically less pragmatic, may still be the best way to measure the effects of an intervention or activity in some cases. For example, surrogate endpoints can be used to describe outcomes in patients with ambiguous conditions or conditions for which there are multiple diagnoses, although care must be taken to ensure that the endpoint is specific and sensitive enough to be valid. For example, a range of ICD codes can be used for diabetes, and collectively the code set can identify most cases, but any individual code will be limited.

For more on specificity and sensitivity, see the Living Textbook Chapter on Acquiring and Using Electronic Health Record Data.

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REFERENCES

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Califf RM, Sugarman J. 2015. Exploring the ethical and regulatory issues in pragmatic clinical trials. Clin Trials. 12:436–441. doi:10.1177/1740774515598334. PMID:26374676.

Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. 2015. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 350:h2147. doi: https://doi.org/10.1136/bmj.h2147. PMID: 25956159.

Citation:

Curtis L, Hernandez A, Weinfurt K. Choosing and Specifying End Points and Outcomes: Meaningful Endpoints. In: Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials. Bethesda, MD: NIH Health Care Systems Research Collaboratory. Available at: http://rethinkingclinicaltrials.org/design/choosing-specifying-end-points-outcomes/meaningful-endpoints/. Updated August 23, 2017.