Are Surrogate Markers Adequate to Assess Cardiovascular Disease Drugs?

Temple, Robert

doi:10.1001/jama.282.8.790

Cited by 301 publications

(194 citation statements)

References 19 publications

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“…Companies may study many surrogate end points and publish results only for those that favor their product. 7,17,21 Data Analysis A study's raw data are generally stored centrally at the company or CRO. Investigators may receive only portions of the data.…”

Section: Trial Designmentioning

confidence: 99%

Uneasy Alliance — Clinical Investigators and the Pharmaceutical Industry

Bodenheimer¹

2000

N Engl J Med

677

389

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Section: Trial Designmentioning

confidence: 99%

Uneasy Alliance — Clinical Investigators and the Pharmaceutical Industry

Bodenheimer¹

2000

N Engl J Med

677

389

View full text Add to dashboard Cite

“…26,27 Surrogate end points (laboratory measures or physical signs intended to be used as substitutes for clinically meaningful end points) may be used to develop some types of therapeutics. 28 Typically more feasible to study compared with clinical outcomes, surrogate end points have the potential to accelerate delivery of new, effective, and safe therapies. Many products currently used by patients with kidney diseases were approved on the basis of surrogate end points, including laboratory tests (like hemoglobin, parathyroid hormone, phosphorus, and potassium).…”

Section: Create An Infrastructure That Increases Clinical Trial Efficmentioning

confidence: 99%

“…Surrogate end points can be used for drug approval when established by definitive studies, or they can be used when deemed "reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit" to secure early "accelerated approval" of a drug to treat "serious or life-threatening diseases, where products provide meaningful therapeutic advantages over existing treatment." 28 This second approach presumes an understanding that additional postapproval studies confirming benefit will be required. 28 …”

Section: Create An Infrastructure That Increases Clinical Trial Efficmentioning

confidence: 99%

Overcoming Barriers in Kidney Health—Forging a Platform for Innovation

Linde

Archdeacon

Breyer

et al. 2016

JASN

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Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.

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“…84 -86 A surrogate biomarker is one that tracks so closely with the clinical outcome that it may substitute for that clinical outcome as a primary endpoint in a registration study. 88,89 To be acceptable as a surrogate, the biomarker must demonstrate that the behavior of the marker with respect to clinical outcome is not an accidental association 90 as had been the case in agents that increased radiographic bone density but did not protect against osteoporotic fractures. 91 Part of that requirement is validation by more than one drug.…”

Section: Most Efficacy Biomarkers Are Not Surrogatesmentioning

confidence: 99%

Translational research in central nervous system drug discovery

Hurko¹,

Ryan²

2005

Neurotherapeutics

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Summary:Of all the therapeutic areas, diseases of the CNS provide the biggest challenges to translational research in this era of increased productivity and novel targets. Risk reduction by translational research incorporates the "learn" phase of the "learn and confirm" paradigm proposed over a decade ago. Like traditional drug discovery in vitro and in laboratory animals, it precedes the traditional phase 1-3 studies of drug development. The focus is on ameliorating the current failure rate in phase 2 and the delays resulting from suboptimal choices in four key areas: initial test subjects, dosing, sensitive and early detection of therapeutic effect, and recognition of differences between animal models and human disease. Implementation of new technologies is the key to success in this emerging endeavor.

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Are Surrogate Markers Adequate to Assess Cardiovascular Disease Drugs?

Cited by 301 publications

References 19 publications

Uneasy Alliance — Clinical Investigators and the Pharmaceutical Industry

Uneasy Alliance — Clinical Investigators and the Pharmaceutical Industry

Overcoming Barriers in Kidney Health—Forging a Platform for Innovation

Translational research in central nervous system drug discovery

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