0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation | Health Care Reform

The Strength of Association Between Surrogate End Points and Survival in Oncology A Systematic Review of Trial-Level Meta-analyses

Vinay Prasad, MD, MPH1; Chul Kim, MD, MPH1; Mauricio Burotto, MD1; Andrae Vandross, MD2
[+] Author Affiliations
1Medical Oncology Service, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
2Division of Medical Oncology, University of California, Los Angeles
JAMA Intern Med. 2015;175(8):1389-1398. doi:10.1001/jamainternmed.2015.2829.
Text Size: A A A
Published online

Importance  The strength of association between surrogate end points and survival in oncology is important to understand because surrogate end points are frequently used in oncology clinical trials, supporting US Food and Drug Administration approvals and National Comprehensive Cancer Network guideline recommendations.

Objective  To identify and evaluate trial-level meta-analyses of randomized clinical trials quantifying the association between a surrogate end point and overall survival in medical oncology. Trial-level correlations test whether treatments that improve the surrogate end point also improve the final end point and are widely considered the strongest evidence to validate a surrogate end point.

Evidence Review  Our literature search was built on earlier reported data sets and updated with Google Scholar and MEDLINE searches conducted on December 26, 2014. For MEDLINE, search terms included (“regression” or “correlation”) and “surrogate” and “end point [or endpoint]” and (“oncology” or “cancer”). For Google scholar, search terms included (“regression” or “correlation”) and “surrogate end point [or endpoint]” and “overall survival” and “trial level.” A total of 108 abstracts were retrieved, and 62 articles were read in full in addition to articles identified through prior reviews.

Findings  We found 36 articles in which 65 specific correlations between a surrogate end point and survival were identified. Surrogate end points were studied in the neoadjuvant, adjuvant, locally advanced, and metastatic settings. The most common sources for trials included in the 36 articles were systematic reviews of the published literature (10 of 36; 28%), and published literature and meeting abstracts (14 of 36; 39%). Four meta-analyses (11%) used a convenience sample, and only 5 studies (14%) attempted to include unpublished trials by surveying clinical trial registries. Among these 5 studies, only 352 of 684 eligible trials (51.1%) were included in the analyses. More than half of reported correlations (34 of 65; 52%) were of low strength (r ≤ 0.7). Approximately a quarter (16 of 65; 25%) were of medium strength (r > 0.7 to r < 0.85), and 15 of 65 (23%) were highly correlated (r ≥ 0.85) with survival.

Conclusions and Relevance  Most trial-level validation studies of surrogate end points in oncology find low correlations with survival. All validation studies use only a subset of available trials. The evidence supporting the use of surrogate end points in oncology is limited.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Figures

Place holder to copy figure label and caption
Figure 1.
Hierarchy of Evidence for Surrogate End Point and Overall Survival Association
Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Distribution of Data Sources Used in the Evaluated Surrogacy End Point Trials
Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Correlations by Treatment Setting

We scored strength of trial-level correlation according to a modification to surrogate criteria proposed by the Institute of Quality and Efficiency in Health Care34: low correlation (r ≤ 0.7), medium strength correlation (r > 0.7 to r < 0.85), and high correlation (r ≥ 0.85).

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

3,747 Views
6 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();