scholarly journals A systematic assessment of preclinical multilaboratory studies and a comparison to single laboratory studies

2021 ◽  
Author(s):  
Victoria Hunniford ◽  
Agnes Grudniewicz ◽  
Dean Ferguson ◽  
Joshua Ryan Montroy ◽  
Emma Grigor ◽  
...  
Keyword(s):  
Study Design ◽  
Treatment Effects ◽  
Median Number ◽  
Risk Of Bias ◽  
Laboratory Studies ◽  
Systematic Assessment ◽  
Reduce Risk ◽  
Mean Differences ◽  
Single Laboratory

Multicentric approaches are widely used in clinical trials to assess generalizability of findings, however they are novel in preclinical experimentation. We synthesized characteristics of multilaboratory studies and quantitatively compared them to single laboratory studies. We systematically identified sixteen in vivo interventional multilaboratory studies and matched them to 100 single laboratory studies by intervention and disease. Differences in standardized mean differences (DSMD) were calculated to compare treatment effects based on study design. The multilaboratory study design was applied across a range of diseases (e.g. stroke, diabetes, trauma). The median number of labs was 4 (range 2-6) and the median sample size was 111 (range 23-384). Multilaboratory studies adhered to practices that reduce risk of bias and were transparently reported. These studies demonstrated significantly smaller treatment effects than single lab studies (DSMD 0.72 [95% confidence interval 0.43-1]). Preclinical multilaboratory studies demonstrate trends that have been well recognized in clinical research (i.e. smaller treatment effects with greater rigour in study design). This approach may provide a method to robustly assess interventions and reproducibility of findings between laboratories.

Multicenter preclinical studies as an innovative method to enhance translation: a systematic review of published studies

2019 ◽  
Author(s):  
Victoria T. Hunniford ◽  
Agnes Grudniewicz ◽  
Dean A. Fergusson ◽  
Emma Grigor ◽  
Casey Lansdell ◽  
...  
Keyword(s):  
Median Number ◽  
Included Study ◽  
Risk Of Bias ◽  
Clinical Translation ◽  
Preclinical Studies ◽  
Preclinical Research ◽  
Multicenter Studies ◽  
Diverse Range ◽  
Completeness Of Reporting

AbstractMulticenter preclinical studies have been suggested as a method to improve reproducibility, generalizability and potential clinical translation of preclinical work. In these studies, multiple independent laboratories collaboratively conduct a research experiment using a shared protocol. The use of a multicenter design in preclinical experimentation is a recent approach and only a handful of preclinical multicenter studies have been published. Here, we systematically identify, assess and synthesize published preclinical multicenter studies investigating interventions using in vivo models. Synthesized data included study methods/design, basic characteristics, outcomes, and barriers and facilitators. Study risk of bias, completeness of reporting and the degree of collaboration were evaluated using established methods. The database searches identified 3095 citations and 12 studies met inclusion criteria. The multicenter study design was applied across a diverse range of diseases including stroke, heart attack, traumatic brain injury, and diabetes. The median number of centers was 4 (range 2-6) and the median sample size was 135 (range 23-384). Most studies had lower risk of bias and higher completeness of reporting than typically seen in single-centered studies. Only four of the twelve studies produced results consistent with previous single-center studies, highlighting a central concern of preclinical research: irreproducibility and poor generalizability of findings from single laboratories. Our review suggests that multicenter preclinical studies may provide a method to robustly assess therapies prior to considering clinical translation. Registered with PROSPERO CRD42018093986.

scholarly journals In Vitro Simulation and In Vivo Assessment of Tooth Wear: A Meta-Analysis of In Vitro and Clinical Research

Materials ◽  
2019 ◽  
Vol 12 (21) ◽  
pp. 3575 ◽  
Author(s):  
Despina Koletsi ◽  
Anna Iliadi ◽  
Theodore Eliades ◽  
George Eliades
Keyword(s):  
Monte Carlo ◽  
Clinical Research ◽  
Study Design ◽  
Tooth Wear ◽  
Risk Of Bias ◽  
Study Selection ◽  
Mean Differences ◽  
Meta Analyses ◽  
Enamel Wear

Tooth wear may be described as a side-effect of occlusal forces that may be further induced by the common use of contemporary prosthetic materials in practice. The purpose of this systematic review was to appraise existing evidence on enamel wear from both in vitro and clinical research and explore whether evidence from these study designs lies on the same direction. Five databases of published and unpublished research were searched without limitations in August 2019 and study selection criteria included in vitro and clinical research on enamel tooth wear. Study selection, data extraction, and risk of bias assessment were done independently and in duplicate. Random effects meta-analyses of standardized mean differences (SMDs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were conducted while a Monte Carlo permutation test for meta-regression on the exploration of the effect of the study design on the reported outcomes was planned. A total of 27 studies (23 in vitro and 4 clinical) were eligible while 12 contributed to meta-analyses. Overall, some concerns were raised for the quality of the existing evidence and the potential for risk of bias. Enamel wear (mm) of antagonist teeth was more pronounced when opposed to conventional porcelain compared to machinable ceramics (SMD = 2.18; 95%CIs: 1.34, 3.02; p < 0.001). Polished zirconia resulted in decreased volumetric enamel wear (mm3) of opposing teeth compared to pure natural enamel (SMD = –1.06; 95%CIs: –1.73, –0.39; p = 0.002). Monolithic zirconia showed evidence of enhanced potential for antagonist wear (μm) compared to natural teeth (WMD = 107.38; 95%CIs: 30.46, 184.30; p = 0.01). Study design did not reveal an effect on the tooth wear outcome for the latter comparison when both clinical and in vitro studies were considered (three studies; Monte Carlo test, p = 0.66). In conclusion, there is an overriding need for additional evidence from clinical research to substantiate the findings from the already existing laboratory simulation studies.

scholarly journals Can we rely on non-randomised studies? Findings from a meta-epidemiological review

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
J C Rejon-Parrilla ◽  
M Salcher-Konrad ◽  
M Nguyen ◽  
K Davis ◽  
P Jonsson ◽  
...  
Keyword(s):  
Health Economic ◽  
Analytical Methods ◽  
Large Scale ◽  
Treatment Effects ◽  
Controlled Trial ◽  
Health Economic Evaluation ◽  
Risk Of Bias ◽  
Economic Decision Making ◽  
Wide Range ◽  
Randomised Controlled

Abstract Background Increasingly, health technology assessment (HTA) agencies must decide whether new medicines should be used routinely in the absence of randomised controlled trial (RCT) data, relying solely on non-randomised studies (NRS), which are at high risk of bias due to confounding. Against the background of increased availability and improved methods to analyse non-randomised data (e.g., propensity score methods and instrumental variables), it is important for decision-makers to have guidance on the analysis and interpretation of NRS to inform health economic evaluation. We therefore aimed to systematically and empirically assess the performance of NRS using different analytical methods as compared to RCTs and develop recommendations on the basis of our findings. Methods We conducted a large-scale meta-epidemiological review to obtain estimates of the discrepancy in treatment effects in matched RCTs and NRS of pharmacologic interventions from published meta-analyses indexed in MEDLINE and the Cochrane Database of Systematic Reviews. We also consulted with HTA bodies, regulators and academics from five European countries to learn from their experience with using non-randomised evidence. Results We compiled the largest dataset of clinical topics with matching RCTs and NRS using various analytical methods to date, covering &gt;100 unique clinical questions. Incorporating information on direction of effect and effect size from &gt;700 unique studies, the dataset can be used to evaluate discrepancies in treatment effects between study designs across a wide range of therapeutic areas. Conclusions An empirically based understanding of the risk of bias in NRS is required in order to promote the adequate use of non-randomised evidence as input for health economic decision-making.

scholarly journals Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

2018 ◽  
Vol 29 (3) ◽  
pp. 321-332 ◽  
Author(s):  
Suleiman Alhaji Muhammad ◽  
Norshariza Nordin ◽  
Sharida Fakurazi
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Conditioned Medium ◽  
Tissue Regeneration ◽  
Therapeutic Benefit ◽  
Risk Of Bias ◽  
Preclinical Studies

AbstractInjury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium inin vivoanimal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

The Effect of Plantago major on Wound Healing in Preclinical Studies: A Systematic Review

2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Preclinical Studies ◽  
Plantago Major ◽  
Best Response ◽  
Meta Analyses

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.

Common Cocklebur (Xanthium strumarium) Resistance to Selected ALS-Inhibiting Herbicides

1997 ◽  
Vol 11 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Christy L. Sprague ◽  
Edward W. Stoller ◽  
Loyd M. Wax
Keyword(s):  
Acetolactate Synthase ◽  
Cross Resistance ◽  
Xanthium Strumarium ◽  
Laboratory Studies ◽  
Whole Plant ◽  
Plant Level

Five biotypes of common cocklebur that were not controlled with acetolactate synthase (ALS)-inhibiting herbicides were tested in greenhouse and laboratory studies to determine the magnitude of resistance and cross-resistance to four ALS-inhibiting herbicides. In vivo inhibition of ALS was also evaluated. Based on phytotoxicity, all five ALS-resistant biotypes of common cocklebur were > 390 times more resistant than the susceptible biotype to imazethapyr. However, only four of these biotypes were also resistant to another imidazolinone, imazaquin. Two biotypes were cross-resistant to the sulfonylurea, chlorimuron, and the triazolopyrimidine sulfonanilide, NAF-75. One biotype demonstrated intermediate susceptibility to imazaquin, chlorimuron, and NAF-75. In all cases, the resistance exhibited at the whole plant level was associated with an insensitive ALS.

scholarly journals The Usefulness of the Pressure Algometer in the Diagnosis and Treatment of Orofacial Pain Patients: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Agata Kamińska ◽  
Bartosz Dalewski ◽  
Ewa Sobolewska
Keyword(s):  
Study Design ◽  
Orofacial Pain ◽  
Pressure Pain Threshold ◽  
Reliability And Validity ◽  
Risk Of Bias ◽  
Small Samples ◽  
Menstrual Phase ◽  
Efficient Approach ◽  
Pressure Algometer ◽  
Pain Patients

Study Design. Data were obtained from PubMed, Dentistry and Oral Sciences Source, ProQuest, Scopus, Medline (EBSCO), and ScienceDirect databases. Literature search was performed from 1 December 2017 through 12 January 2018. The titles and abstracts from electronic search results were screened for keywords and evaluated by two observers, with the following inclusion criteria: published since 1997, written in English, and encompassing human research. Exclusion criteria were as follows: articles published earlier than 1997, not written in English, animal studies, studies with the use of medicaments, and articles examining receptor interactions. Objectives. The pressure pain threshold (PPT) may be an efficient approach to screen and evaluate orofacial pain. However, the results of previous PPT studies have varied greatly. The aim of this paper was to determine whether the PPT is an efficient approach for screening and evaluating orofacial pain. Methods. The search yielded 123 articles. After removal of duplicates and screening of abstracts, 32 articles were selected for further evaluation. The Cochrane Collaboration tool for assessing the risk of bias was used for the evaluation of the studies. Results. The studies covered a total of 4403 adult patients, aged 16-62, and 30 children. The studies investigated the reliability and validity of the PPT (measured by a pressure algometer) in TMD patients. The PPT was investigated in relation to headache, menstrual cycle, oral contraception, occlusal interference, and occlusal appliances. Generally, the risk of bias was low to unclear. Some structural limitations were inherent in the studies, such as small samples and short duration of the testing involved. Also, the analyzed studies lacked consistency in study design and patient management. Pressure increase values differed from 20 kPa/s to 50 kPa/s and from 0.5 kg/cm2/s to 2 kg/cm2/s. Descriptions of the PPT examination points also varied, from very precise and repeatable to a simple listing of anatomical points. The number of measurements varied from 1 to 5 at each visit. The intervals ranged from 5 seconds to 15 minutes. However, some studies confirmed that the pressure algometer is an effective tool for determining the source of orofacial pain. Conclusions. Based on the analyzed articles, the authors argue that the PPT is not an efficient approach for screening and evaluating orofacial pain. What is more, it should not be used as the only diagnostics tool for patients with orofacial pain. Importantly, however, additional factors should be considered in the future for the evaluation of the PPT, including body symmetry and posture, hormone levels and the menstrual phase in women, and the use of medications and its influence on the PPT. Further clinical trials should also be performed on the PPT, examining head and neck pain patients, with more precise study design and larger samples.

scholarly journals Effectiveness of orthodontic temporary anchorage devices in canine retraction and anchorage preservation during the two-step technique: a systematic review and meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Haonan Tian ◽  
Congman Xie ◽  
Min Lin ◽  
Hongmei Yang ◽  
Aishu Ren
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Canine Retraction ◽  
Temporary Anchorage Devices ◽  
The Mean ◽  
Mean Differences ◽  
Implant Anchorage

Abstract Background Temporary anchorage devices have been used for decades in orthodontic practice for many applications. The aim of this systematic review was to assess the effectiveness of orthodontic temporary anchorage devices in canine retraction during the two-step technique. Methods A search was systematically performed for articles published prior to June 30, 2019 in five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus). The risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials (CCTs). The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. A meta-analysis with a random-effects model for comparable outcomes was carried out. Results Three RCTs and five CCTs were finally included. Meta-analysis showed a significant increase not only in anchorage preservation in the implant anchorage group in both the maxilla (1.56 mm, 95% CI: 1.14 to 1.98, P < 0.00001) and the mandible (1.62 mm, 95% CI: 1.24 to 2.01, P < 0.00001) but also in canine retraction in the implant anchorage group in both the maxilla (0.43 mm, 95% CI: 0.16 to 0.69, P = 0.001) and the mandible (0.26 mm, 95% CI: 0.02 to 0.49, P = 0.03). Conclusions There is very low-quality evidence showing that implant anchorage is more efficient than conventional anchorage during canine retraction. Additional high-quality studies are needed.

scholarly journals Efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis: a systematic review protocol

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1011
Author(s):  
Camille Maltais-Bilodeau ◽  
Ewa Henckel ◽  
Kelly D. Cobey ◽  
Nadera Ahmadzai ◽  
Becky Skidmore ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Necrotizing Enterocolitis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bowel Perforation ◽  
Risk Of Bias ◽  
Sufficient Evidence ◽  
Preclinical Models

Introduction: Necrotizing enterocolitis is an acute inflammatory disease of the intestine that can lead to necrosis and bowel perforation. It is a severe complication of preterm birth. It’s mortality rate is up to 50% and survival after necrotizing enterocolitis leads to long-term complications. The current treatment is supportive and includes bowel rest and decompression and antibiotics. Thus, new treatments are necessary to reduce mortality and morbidity. Mesenchymal stromal cells are known to have anti-inflammatory properties and might be a promising option for treatment. Here we present a protocol for a systematic review with the aim to explore the efficacy of cell therapies with mesenchymal stromal cells in animal models of necrotizing enterocolitis. The primary outcome is histological signs of necrotizing enterocolitis. Additional outcomes include survival, bowel perforation, gut permeability, gut motility, levels of inflammatory markers, cytokine levels and adverse events. Methods: We will conduct a systematic search of MEDLINE, Embase, and Web of Science databases. The retrieved records will be screened individually by two investigators. We will include all preclinical in vivo animal models of experimentally induced necrotizing enterocolitis that evaluate the efficacy of mesenchymal stromal cells or other cell therapy treatments. Outcome data will be extracted from each article and risk of bias assessment performed. Funnel plots and SYRCLE’s risk of bias tool for animal studies will be used. Data will be reported as ratios, divided in predefined subgroups where relevant. Conclusions: This systematic review aims to examine the efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis and whether there is sufficient evidence to support a clinical trial of efficacy and safety of the treatment with mesenchymal stromal cells in infants with necrotizing enterocolitis.

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