lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Incidence of Total Joint Replacements from the Prospective Epidemiologic Risk Factor Study: Considerations for Event Driven Clinical Trial Design

14 Pages Posted: 18 Nov 2018

See all articles by Cecilie Bager

Cecilie Bager

ProScion

Morten Karsdal

Nordic Bioscience

Asger Bihlet

Nordic Bioscience

Christian Thudium

Nordic Bioscience

Inger Byrjalsen Byrjalsen

Nordic Bioscience

Anne C. Bay-Jensen

Nordic Bioscience

More...

Abstract

Background: Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used as an endpoint in event-driven clinical trials within a reasonable duration. We explored the incidence of TJR in the Prospective Epidemiologic Risk Factor (PERF I) study.  

Methods: A total of 5,855 Danish postmenopausal women aged 49-88 enrolled in the PERF I study during 1999-2001 (baseline). Three-, six- and twelve-year follow-up data from the Danish National Patient Registry was collected, including occurrence of TJR and OA diagnosis. At baseline the women were asked whether they had OA.  

Findings: The TJR women were on average 1 year older (p<0.001) and heavier (p<0.001), compared to women with no TJR in the follow-up period. The 3-, 6- and 12-year cumulative incidences were 1.1, 2.4 and 6.0% for TKR, and 2.1, 4.4 and 9.3% for THR. For those with an OA diagnosis at baseline the respective incidences were 2.7, 5.6 and 11.7% and 3.9, 7.2 and 13.6%.  

Interpretation: Within 3, 6 or 12 years TJR incidences were double for women with an OA diagnosis compared to the all-comer population. TJRs are frequent amongst elderly women with OA and it is, therefore, feasible to conduct event-driven clinical trials where TJR is the endpoint demonstrating clinical benefit of a novel disease-modifying OA drug (DMOAD).  

Funding Statement: The Danish Research Foundation funded the PERF I study.

Declaration of Interests: Bager is employed at ProScion. Karsdal, Bihlet, Thudium, Byrjalsen and Bay-Jensen are employed at Nordic Bioscience. Karsdal, Bihlet, and Bay-Jensen holds stocks in Nordic Bioscience.

Ethics Approval Statement: The PERF I study was carried out in accordance with applicable regulatory and ethical guidelines, and the study protocol was approved by the local ethics committees. All participants signed an informed consent.

Keywords: total joint replacements, osteoarthritis, clinical trial design, postmenopausal women, register

Suggested Citation

Bager, Cecilie and Karsdal, Morten and Bihlet, Asger and Thudium, Christian and Byrjalsen, Inger Byrjalsen and Bay-Jensen, Anne C., Incidence of Total Joint Replacements from the Prospective Epidemiologic Risk Factor Study: Considerations for Event Driven Clinical Trial Design (November 14, 2018). Available at SSRN: https://ssrn.com/abstract=3286112 or http://dx.doi.org/10.2139/ssrn.3286112

Cecilie Bager (Contact Author)

ProScion ( email )

Herleev
Denmark

Morten Karsdal

Nordic Bioscience

Herlev
Denmark

Asger Bihlet

Nordic Bioscience

Herlev
Denmark

Christian Thudium

Nordic Bioscience

Herlev
Denmark

Inger Byrjalsen Byrjalsen

Nordic Bioscience

Herlev
Denmark

Anne C. Bay-Jensen

Nordic Bioscience

Herlev
Denmark