Diabetes clinical trials

Helped or hindered by the current shift in regulatory requirements?

Faiez Zannad, Wendy Gattis Stough, Stuart J. Pocock, Peter Sleight, William Cushman, John G.F. Cleland, John J.V. McMurray, Eva Lonn, Nancy L. Geller, Hans Wedel, Eric Abadie, Angeles Alonso-Garcia, Bertram Pitt

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

Glycaemic control is an inadequate surrogate marker of cardiovascular event reduction in patients with type 2 diabetes. Clinical trials to date have been unsuccessful in identifying a therapeutic approach that addresses the underlying problem in diabetes (glycaemic control) and reduces cardiovascular risk. The potential for some agents to increase the risk of cardiovascular events has led to substantial changes in regulatory requirements for new anti-diabetic therapies. These requirements, while key to ensuring the cardiovascular safety of new agents, fail to emphasize the need to show clinical benefits, such as less visual impairment, less need for dialysis, or fewer cardiovascular events and deaths. Changes in test results such as glycaemic control, serum creatinine, micro-albuminuria, or retinopathy are inadequate surrogates. Regulators should consider the potential advantages of offering extended patent protection in order to encourage companies to conduct long-term trials in diabetes and many other chronic medical conditions. Cooperative efforts among physicians, clinical trialists, regulators, and sponsors are needed to address unresolved issues including re-defining therapeutic targets that are meaningful to patients with diabetes, determining the appropriate length of follow-up for future trials, and considering the ethical and operational challenges of non-inferiority designs. Published on behalf of the European Society of Cardiology.

Original languageEnglish (US)
Pages (from-to)1049-1057
Number of pages9
JournalEuropean Heart Journal
Volume33
Issue number9
DOIs
StatePublished - May 1 2012

Fingerprint

Clinical Trials
Albuminuria
Vision Disorders
Type 2 Diabetes Mellitus
Dialysis
Creatinine
Therapeutics
Biomarkers
Physicians
Safety
Serum

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Zannad, F., Stough, W. G., Pocock, S. J., Sleight, P., Cushman, W., Cleland, J. G. F., ... Pitt, B. (2012). Diabetes clinical trials: Helped or hindered by the current shift in regulatory requirements? European Heart Journal, 33(9), 1049-1057. https://doi.org/10.1093/eurheartj/ehr437

Diabetes clinical trials : Helped or hindered by the current shift in regulatory requirements? / Zannad, Faiez; Stough, Wendy Gattis; Pocock, Stuart J.; Sleight, Peter; Cushman, William; Cleland, John G.F.; McMurray, John J.V.; Lonn, Eva; Geller, Nancy L.; Wedel, Hans; Abadie, Eric; Alonso-Garcia, Angeles; Pitt, Bertram.

In: European Heart Journal, Vol. 33, No. 9, 01.05.2012, p. 1049-1057.

Research output: Contribution to journalReview article

Zannad, F, Stough, WG, Pocock, SJ, Sleight, P, Cushman, W, Cleland, JGF, McMurray, JJV, Lonn, E, Geller, NL, Wedel, H, Abadie, E, Alonso-Garcia, A & Pitt, B 2012, 'Diabetes clinical trials: Helped or hindered by the current shift in regulatory requirements?', European Heart Journal, vol. 33, no. 9, pp. 1049-1057. https://doi.org/10.1093/eurheartj/ehr437
Zannad, Faiez ; Stough, Wendy Gattis ; Pocock, Stuart J. ; Sleight, Peter ; Cushman, William ; Cleland, John G.F. ; McMurray, John J.V. ; Lonn, Eva ; Geller, Nancy L. ; Wedel, Hans ; Abadie, Eric ; Alonso-Garcia, Angeles ; Pitt, Bertram. / Diabetes clinical trials : Helped or hindered by the current shift in regulatory requirements?. In: European Heart Journal. 2012 ; Vol. 33, No. 9. pp. 1049-1057.
@article{8d614f5c068b4f25b56b3ef829a86add,
title = "Diabetes clinical trials: Helped or hindered by the current shift in regulatory requirements?",
abstract = "Glycaemic control is an inadequate surrogate marker of cardiovascular event reduction in patients with type 2 diabetes. Clinical trials to date have been unsuccessful in identifying a therapeutic approach that addresses the underlying problem in diabetes (glycaemic control) and reduces cardiovascular risk. The potential for some agents to increase the risk of cardiovascular events has led to substantial changes in regulatory requirements for new anti-diabetic therapies. These requirements, while key to ensuring the cardiovascular safety of new agents, fail to emphasize the need to show clinical benefits, such as less visual impairment, less need for dialysis, or fewer cardiovascular events and deaths. Changes in test results such as glycaemic control, serum creatinine, micro-albuminuria, or retinopathy are inadequate surrogates. Regulators should consider the potential advantages of offering extended patent protection in order to encourage companies to conduct long-term trials in diabetes and many other chronic medical conditions. Cooperative efforts among physicians, clinical trialists, regulators, and sponsors are needed to address unresolved issues including re-defining therapeutic targets that are meaningful to patients with diabetes, determining the appropriate length of follow-up for future trials, and considering the ethical and operational challenges of non-inferiority designs. Published on behalf of the European Society of Cardiology.",
author = "Faiez Zannad and Stough, {Wendy Gattis} and Pocock, {Stuart J.} and Peter Sleight and William Cushman and Cleland, {John G.F.} and McMurray, {John J.V.} and Eva Lonn and Geller, {Nancy L.} and Hans Wedel and Eric Abadie and Angeles Alonso-Garcia and Bertram Pitt",
year = "2012",
month = "5",
day = "1",
doi = "10.1093/eurheartj/ehr437",
language = "English (US)",
volume = "33",
pages = "1049--1057",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Diabetes clinical trials

T2 - Helped or hindered by the current shift in regulatory requirements?

AU - Zannad, Faiez

AU - Stough, Wendy Gattis

AU - Pocock, Stuart J.

AU - Sleight, Peter

AU - Cushman, William

AU - Cleland, John G.F.

AU - McMurray, John J.V.

AU - Lonn, Eva

AU - Geller, Nancy L.

AU - Wedel, Hans

AU - Abadie, Eric

AU - Alonso-Garcia, Angeles

AU - Pitt, Bertram

PY - 2012/5/1

Y1 - 2012/5/1

N2 - Glycaemic control is an inadequate surrogate marker of cardiovascular event reduction in patients with type 2 diabetes. Clinical trials to date have been unsuccessful in identifying a therapeutic approach that addresses the underlying problem in diabetes (glycaemic control) and reduces cardiovascular risk. The potential for some agents to increase the risk of cardiovascular events has led to substantial changes in regulatory requirements for new anti-diabetic therapies. These requirements, while key to ensuring the cardiovascular safety of new agents, fail to emphasize the need to show clinical benefits, such as less visual impairment, less need for dialysis, or fewer cardiovascular events and deaths. Changes in test results such as glycaemic control, serum creatinine, micro-albuminuria, or retinopathy are inadequate surrogates. Regulators should consider the potential advantages of offering extended patent protection in order to encourage companies to conduct long-term trials in diabetes and many other chronic medical conditions. Cooperative efforts among physicians, clinical trialists, regulators, and sponsors are needed to address unresolved issues including re-defining therapeutic targets that are meaningful to patients with diabetes, determining the appropriate length of follow-up for future trials, and considering the ethical and operational challenges of non-inferiority designs. Published on behalf of the European Society of Cardiology.

AB - Glycaemic control is an inadequate surrogate marker of cardiovascular event reduction in patients with type 2 diabetes. Clinical trials to date have been unsuccessful in identifying a therapeutic approach that addresses the underlying problem in diabetes (glycaemic control) and reduces cardiovascular risk. The potential for some agents to increase the risk of cardiovascular events has led to substantial changes in regulatory requirements for new anti-diabetic therapies. These requirements, while key to ensuring the cardiovascular safety of new agents, fail to emphasize the need to show clinical benefits, such as less visual impairment, less need for dialysis, or fewer cardiovascular events and deaths. Changes in test results such as glycaemic control, serum creatinine, micro-albuminuria, or retinopathy are inadequate surrogates. Regulators should consider the potential advantages of offering extended patent protection in order to encourage companies to conduct long-term trials in diabetes and many other chronic medical conditions. Cooperative efforts among physicians, clinical trialists, regulators, and sponsors are needed to address unresolved issues including re-defining therapeutic targets that are meaningful to patients with diabetes, determining the appropriate length of follow-up for future trials, and considering the ethical and operational challenges of non-inferiority designs. Published on behalf of the European Society of Cardiology.

UR - http://www.scopus.com/inward/record.url?scp=84860637034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860637034&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehr437

DO - 10.1093/eurheartj/ehr437

M3 - Review article

VL - 33

SP - 1049

EP - 1057

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 9

ER -