+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments



Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments



Plos Medicine 10(7): E1001489



The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address. We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria--most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation. By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice. Please see later in the article for the Editors' Summary.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 056565549

Download citation: RISBibTeXText

PMID: 23935460

DOI: 10.1371/journal.pmed.1001489


Related references

The usefulness of systematic reviews of animal experiments for the design of preclinical and clinical studies. Ilar Journal 55(3): 427-437, 2015

Quality of Reporting and Adherence to ARRIVE Guidelines in Animal Studies for Chagas Disease Preclinical Drug Research: A Systematic Review. Plos Neglected Tropical Diseases 9(11): E0004194, 2016

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device-related infection. Journal of Orthopaedic Research 2019, 2019

A systematic review of systematic reviews and meta-analyses of animal experiments with guidelines for reporting. Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes 41(7): 1245-1258, 2006

A systematic review highlights threats to validity in studies of barriers to cancer trial participation. Journal of Clinical Epidemiology 60(10): 990-1001, 2007

The study design elements employed by researchers in preclinical animal experiments from two research domains and implications for automation of systematic reviews. Plos One 13(6): E0199441, 2018

Systematic reviews and meta-analyses of preclinical studies: publication bias in laboratory animal experiments. Laboratory Animals 45(4): 225-230, 2012

Design and Reporting of Targeted Anticancer Preclinical Studies: A Meta-Analysis of Animal Studies Investigating Sorafenib Antitumor Efficacy. Cancer Research 76(16): 4627-4636, 2017

Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review. Plos One 11(1): E0147170, 2016

Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol. Systematic Reviews 5: 89, 2017

Impact of hyperglycemia on the efficacy of chemotherapy-A systematic review of preclinical studies. Critical Reviews in Oncology/Hematology 113: 235-241, 2017

Efficacy and Mechanisms of Aerobic Exercise on Cancer Initiation, Progression, and Metastasis: A Critical Systematic Review of In Vivo Preclinical Data. Cancer Research 76(14): 4032-4050, 2017

Osteogenic Potential of Dental Mesenchymal Stem Cells in Preclinical Studies: A Systematic Review Using Modified ARRIVE and CONSORT Guidelines. Stem Cells International 2015: 378368, 2015

Applying the Taxonomy of Validity Threats from Mainstream Research Design to Single-Case Experiments in Applied Behavior Analysis. Behavior Analysis in Practice 11(3): 228-240, 2018

Efficacy of stem cells on the healing of peri-implant defects: systematic review of preclinical studies. Clinical and Experimental Dental Research 2(1): 18-34, 2016