scholarly journals Can prospective systematic reviews of animal studies improve clinical translation?

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Pandora Pound ◽  
Merel Ritskes-Hoitinga
Keyword(s):  
Clinical Trials ◽  
Systematic Reviews ◽  
Animal Studies ◽  
Poor Quality ◽  
Human Studies ◽  
Clinical Knowledge ◽  
Safety And Efficacy ◽  
High Quality Evidence ◽  
Animal Data

AbstractSystematic reviews are powerful tools with the potential to generate high quality evidence. Their application to animal studies has been instrumental in exposing the poor quality of these studies, as well as a catalyst for improvements in study design, conduct and reporting. It has been suggested that prospective systematic reviews of animal studies (i.e. systematic reviews conducted prior to clinical trials) would allow scrutiny of the preclinical evidence, providing valuable information on safety and efficacy, and helping to determine whether clinical trials should proceed. However, while prospective systematic reviews allow valuable scrutiny of the preclinical animal data, they are not necessarily able to reliably predict the safety and efficacy of an intervention when trialled in humans. Consequently, they may not reliably safeguard humans participating in clinical trials and might potentially result in lost opportunities for beneficial clinical treatments. Furthermore, animal and human studies are often conducted concurrently, which not only makes prospective systematic reviews of animal studies impossible, but suggests that animal studies do not inform human studies in the manner presumed. We suggest that this points to a confused attitude regarding animal studies, whereby tradition demands that they precede human studies but practice indicates that their findings are often ignored. We argue that it is time to assess the relative contributions of animal and human research in order to better understand how clinical knowledge is actually produced.

scholarly journals Importance of Systematic Reviews and Meta-analyses of Animal Studies: Challenges for Animal-to-Human Translation

2020 ◽  
Vol 59 (5) ◽  
pp. 469-477
Author(s):  
Zahra Bahadoran ◽  
Parvin Mirmiran ◽  
Khosrow Kashfi ◽  
Asghar Ghasemi
Keyword(s):  
Systematic Reviews ◽  
Animal Studies ◽  
Animal Experiments ◽  
Clinical Applications ◽  
Current Evidence ◽  
Exclusion Criteria ◽  
Safety And Efficacy ◽  
Balanced Assessment ◽  
Animal Data ◽  
Meta Analyses

Results of animal experiments are used for understanding the pathophysiology of diseases, assessing safety and efficacy of newly developed drugs, and monitoring environmental health hazards among others. Systematic reviews and meta-analyses of animal data are important tools to condense animal evidence and translate the data into practical clinical applications. Such studies are conducted to explore heterogeneity, to generate new hypotheses about pathophysiology and treatment, to design new clinical trial modalities, and to test the efficacy and the safety of the various interventions. Here, we provide an overview regarding the importance of systematic reviews and meta-analyses of animal data and discuss common challenges and their potential solutions. Current evidence highlights various problems and challenges that surround these issues, including lack of generalizability of data obtained from animal models, failure in translating data obtained from animals to humans, poor experimental design and the reporting of the animal studies, heterogeneity of the data collected, and methodologic weaknesses of animal systematic reviews and meta-analyses. Systematic reviews and meta-analyses of animal studies can catalyze translational processes more effectively if they focus on a well-defined hypothesis along with addressing clear inclusion and exclusion criteria, publication bias, heterogeneity of the data, and a coherent and well-balanced assessment of studies' quality.

scholarly journals A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the USA from 2016 to 2019

2021 ◽  
pp. 1-22
Author(s):  
Sebastian Jugl ◽  
Aimalohi Okpeku ◽  
Brianna Costales ◽  
Earl J. Morris ◽  
Golnoosh Alipour-Haris ◽  
...  
Keyword(s):  
Systematic Reviews ◽  
The Body ◽  
Medical Cannabis ◽  
High Quality ◽  
Chronic Noncancer Pain ◽  
High Quality Evidence ◽  
Improved Outcomes ◽  
Noncancer Pain ◽  
Study Setting

In 2017, a National Academies of Sciences, Engineering, and Medicine (NASEM) report comprehensively evaluated the body of evidence regarding cannabis health effects through the year 2016. The objectives of this study are to identify and map the most recently (2016–2019) published literature across approved conditions for medical cannabis and to evaluate the quality of identified recent systematic reviews, published following the NASEM report. Following the literature search from 5 databases and consultation with experts, 11 conditions were identified for evidence compilation and evaluation: amyotrophic lateral sclerosis, autism, cancer, chronic noncancer pain, Crohn’s disease, epilepsy, glaucoma, human immunodeficiency virus/AIDS, multiple sclerosis (MS), Parkinson’s disease, and posttraumatic stress disorder. A total of 198 studies were included after screening for condition-specific relevance and after imposing the following exclusion criteria: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome definition, intervention definition, sample size, study setting, and reported effect size. Few completed randomized controlled trials (RCTs) were identified. Studies classified as systematic reviews were graded using the Assessing the Methodological Quality of Systematic Reviews-2 tool to evaluate the quality of evidence. Few high-quality systematic reviews were available for most conditions, with the exceptions of MS (9 of 9 graded moderate/high quality; evidence for 2/9 indicating cannabis improved outcomes; evidence for 7/9 indicating cannabis inconclusive), epilepsy (3 of 4 graded moderate/high quality; 3 indicating cannabis improved outcomes; 1 indicating cannabis inconclusive), and chronic noncancer pain (12 of 13 graded moderate/high quality; evidence for 7/13 indicating cannabis improved outcomes; evidence from 6/7 indicating cannabis inconclusive). Among RCTs, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic noncancer pain). The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions, and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.

scholarly journals Measurement properties of patient-reported outcome measures (PROMs) in hyperhidrosis: a systematic review

2021 ◽  
Author(s):  
Michaela Gabes ◽  
Helge Knüttel ◽  
Gesina Kann ◽  
Christina Tischer ◽  
Christian J. Apfelbacher
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Patient Reported Outcome Measures ◽  
Patient Reported Outcome ◽  
Measurement Properties ◽  
High Quality ◽  
High Quality Evidence ◽  
Patient Reported ◽  
Quality Evidence

Abstract Purpose To critically appraise, compare and summarize the quality of all existing PROMs that have been validated in hyperhidrosis to at least some extend by applying the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Thereby, we aim to give a recommendation for the use of PROMs in future clinical trials in hyperhidrosis. Methods We considered studies evaluating, describing or comparing measurement properties of PROMs as eligible. A systematic literature search in three big databases (MEDLINE, EMBASE and Web of Science) was performed. We assessed the methodological quality of each included study using the COSMIN Risk of Bias checklist. Furthermore, we applied predefined quality criteria for good measurement properties and finally, graded the quality of the evidence. Results Twenty-four articles reporting on 13 patient-reported outcome measures were included. Three instruments can be further recommended for use. They showed evidence for sufficient content validity and moderate- to high-quality evidence for sufficient internal consistency. The methodological assessment showed existing evidence gaps for eight other PROMs, which therefore require further validation studies to make an adequate decision on their recommendation. The Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) and the short-form health survey with 36 items (SF-36) were the only questionnaires not recommended for use in patients with hyperhidrosis due to moderate- to high-quality evidence for insufficient measurement properties. Conclusion Three PROMs, the Hyperhidrosis Quality of Life Index (HidroQoL), the Hyperhidrosis Questionnaire (HQ) and the Sweating Cognitions Inventory (SCI), can be recommended for use in future clinical trials in hyperhidrosis. Results obtained with these three instruments can be seen as trustworthy. Nevertheless, further validation of all three PROMs is desirable. Systematic review registration PROSPERO CRD42020170247

scholarly journals Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Joel Jihwan Hwang ◽  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Clinical Applications ◽  
Clinical Settings ◽  
Positive Outcomes ◽  
Joint Function ◽  
Safety And Efficacy ◽  
High Expectations ◽  
Recent Developments

Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.

scholarly journals Patient-important outcomes in systematic reviews: Poor quality of evidence

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0195460 ◽  
Author(s):  
Youri Yordanov ◽  
Agnes Dechartres ◽  
Philippe Ravaud
Keyword(s):  
Systematic Reviews ◽  
Poor Quality ◽  
Quality Of Evidence

scholarly journals Oxytocin and Naltrexone Successfully Treat Hypothalamic Obesity in a Boy Post-Craniopharyngioma Resection

2017 ◽  
Vol 103 (2) ◽  
pp. 370-375 ◽  
Author(s):  
Eugenie A Hsu ◽  
Jennifer L Miller ◽  
Francisco A Perez ◽  
Christian L Roth
Keyword(s):  
Parental Monitoring ◽  
Animal Studies ◽  
Phase 1 ◽  
Poor Quality ◽  
Free Access ◽  
Phase 2 ◽  
Z Score ◽  
Hypothalamic Obesity ◽  
Food Seeking

Abstract Context Hypothalamic obesity, a treatment-resistant condition common to survivors of craniopharyngioma (CP), is strongly associated with a poor quality of life in this population. Oxytocin (OT), a hypothalamic neuropeptide, has been shown to play a role in the regulation of energy balance and to have anorexigenic effects in animal studies. Naltrexone (NAL), an opiate antagonist, has been shown to deter hedonic eating and to potentiate OT’s effects. Design In this parent-observed study, we tested the administration of intranasal OT for 10 weeks (phase 1), followed by a combination of intranasal OT and NAL for 38 weeks (phase 2) in a 13-year-old male with confirmed hypothalamic obesity and hyperphagia post-CP resection. Treatment resulted in 1) reduction in body mass index (BMI) z score from 1.77 to 1.49 over 10 weeks during phase 1; 2) reduction in BMI z score from 1.49 to 0.82 over 38 weeks during phase 2; 3) reduced hyperphagia during phases 1 and 2; 4) continued hedonic high-carbohydrate food-seeking in the absence of hunger during phases 1 and 2; and 5) sustained weight reduction during decreased parental monitoring and free access to unlocked food in the home during the last 10 weeks of phase 2. Conclusion This successful intervention of CP-related hypothalamic obesity and hyperphagia by OT alone and in combination with NAL is promising for conducting future studies of this treatment-recalcitrant form of obesity.

scholarly journals Endoscopically applied biodegradable stent in a pediatric tracheomalacia model

2020 ◽  
Author(s):  
Ji Suk Choi ◽  
Jungirl Seok ◽  
Min Rye Eom ◽  
Eungee Jung ◽  
Su A Park ◽  
...  
Keyword(s):  
Clinical Trials ◽  
New Zealand ◽  
Animal Studies ◽  
Pediatric Patients ◽  
Survival Duration ◽  
Biodegradable Stent ◽  
Safety And Efficacy ◽  
Distal Airway ◽  
New Zealand White Rabbits ◽  
Mucosal Changes

Objectives: A polydioxanone (PDO) stent has been developed to treat tracheomalacia in pediatric patients. However, its safety and efficacy need to be verified in animal studies before clinical trials in patients can be conducted. This study evaluated the safety and efficacy of a PDO stent in normal and tracheomalacia model rabbits. Methods: In all, 29 New Zealand white rabbits were used, 13 for evaluating the biocompatibility of the PDO stent in normal rabbits and 16 for the creation of a tracheomalacia model. Of the 16, the tracheomalacia model was successfully established in 12 rabbits; PDO stents were placed in 8 of these rabbits.Results: The PDO stent was successfully positioned in the trachea of the normal rabbits using an endoscopic approach, and its degradation was observed 10 weeks later. The stent fragments did not induce distal airway obstruction or damage, and mucosal changes that occurred after stent placement were reversed after degradation. The same procedure was performed on the tracheomalacia model rabbits. The survival duration of the tracheomalacia rabbits with and without stents was 49.0

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