The translational challenge in the development of new and effective therapies for endometriosis: a review of confidence from published preclinical efficacy studies

Pullen, Nick; Birch, Claire L.; Douglas, Garry J.; Hussain, Qasim; Pruimboom‐Brees, Ingrid; Walley, Rosalind

doi:10.1093/humupd/dmr030

Cited by 34 publications

(39 citation statements)

References 66 publications

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“…It is estimated that 51%-89% of published research cannot be reproduced in other laboratories. [18][19][20][21][22] This problem has been highlighted by a number of recent, high-profile commentaries from the pharmaceutical industry, 18,19,23 funding agencies, including the National Institutes of Health, 24,25 scientific journals, 26,27 veterinarians, 28 academics, and biostatisticians. [29][30][31][32][33][34][35][36] This is of particular importance when animal models are used to advance the development of clinical therapeutics.…”

Section: Common Concerns About Preclinical Study Design and Reportingmentioning

confidence: 99%

“…Systematic reviews have identified recurring methodologic weaknesses in preclinical studies. 18,19,23,24,34,35 Vulnerabilities include errors in statistical design (inadequate power, ad hoc, interim, and retrospective end point analysis), lack of randomization and blinding, and incomplete methods reporting. In addition, lack of transparency in data reporting allows investigators to selectively report positive results without including information about experiments that fail to support the desired effect.…”

Section: Common Concerns About Preclinical Study Design and Reportingmentioning

confidence: 99%

“…18,19,23,24,34,35 Only one study described prespecified end points (primary outcome measures) and used them to perform a power analysis and determine the sample size required to detect a specified effect size. 59 Designing adequately powered animal studies is just as important as in clinical studies, because underpowered studies may lead to both false-negative and falsepositive results.…”

Section: Preclinical Study Design and Reportingmentioning

confidence: 99%

“…Although we recognize that these weaknesses in preclinical AKI research are shared with other areas of preclinical research that have already been extensively reported, 18,19,23,24,34,35 there remain significant challenges to implementing change. Despite the large number of publications on deficiencies in preclinical research design in other areas of medicine, an expectation gap remains between the academic research community and pharmaceutical industry.…”

Section: Recommendations Implementation and Challengesmentioning

confidence: 99%

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Bridging Translation by Improving Preclinical Study Design in AKI

Caestecker

Humphreys

Liu

et al. 2015

Journal of the American Society of Nephrology

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Despite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrastinduced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development.

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Section: Common Concerns About Preclinical Study Design and Reportingmentioning

confidence: 99%

Section: Common Concerns About Preclinical Study Design and Reportingmentioning

confidence: 99%

Section: Preclinical Study Design and Reportingmentioning

confidence: 99%

Section: Recommendations Implementation and Challengesmentioning

confidence: 99%

See 2 more Smart Citations

Bridging Translation by Improving Preclinical Study Design in AKI

Caestecker

Humphreys

Liu

et al. 2015

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The authors concluded that greater scrutiny of the preclinical efficacy of models, end points, and experimental designs are needed if the desire of translating novel treatment approaches is to be realized in women with endometriosis. 115 Recommendation. Appropriate animal and in vitro models for preclinical studies of endometriosis therapies should be agreed upon by the endometriosis research community.…”

Section: Animal and Other Preclinical Modelsmentioning

confidence: 99%

Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France

D’Hooghe²,

et al. 2013

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Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008. 1 A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.

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A mass spectrometric insight into the origins of benign gynecological disorders

Yang

Lau

Yao

et al. 2015

Mass Spectrometry Reviews

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Applications of mass spectrometry (MS) are rapidly expanding and encompass molecular and cellular biology. MS aids in the analysis of in vivo global molecular alterations, identifying potential biomarkers which may improve diagnosis and treatment of various pathologies. MS has added new dimensionality to medical research. Pioneering gynecologists now study molecular mechanisms underlying female reproductive pathology with MS-based tools. Although benign gynecologic disorders including endometriosis, adenomyosis, leiomyoma, and polycystic ovarian syndrome (PCOS) carry low mortality rates, they cause significant physical, mental, and social detriments. Additionally, some benign disorders are unfortunately associated with malignancies. MS-based technology can detect malignant changes in formerly benign proteomes and metabolomes with distinct advantages of speed, sensitivity, and specificity. We present the use of MS in proteomics and metabolomics, and summarize the current understanding of the molecular pathways concerning female reproductive anatomy. Highlight discoveries of novel protein and metabolite biomarkers via MS-based technology, we underscore the clinical application of these techniques in the diagnosis and management of benign gynecological disorders. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:450-470, 2017.

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The translational challenge in the development of new and effective therapies for endometriosis: a review of confidence from published preclinical efficacy studies

Abstract: Greater scrutiny of the preclinical efficacy models, end-points and experimental designs is needed if the desire of translating novel treatment approaches is to be realized for women with endometriosis.

Cited by 34 publications

References 66 publications

Bridging Translation by Improving Preclinical Study Design in AKI

Bridging Translation by Improving Preclinical Study Design in AKI

Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France

A mass spectrometric insight into the origins of benign gynecological disorders

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