A systematic review of animal and human data comparing the nasal potential difference test between cystic fibrosis and control.

The nasal potential difference test (nPD) is an electrophysiological measurement which is altered in patients and animal models with cystic fibrosis (CF). Because protocols and outcomes vary substantially between laboratories, there are concerns over its validity and precision. We performed a systematic literature review (SR) of the nPD to answer the following review questions: A. Is the nasal potential difference similarly affected in CF patients and animal models?", and B. "Is the nPD in human patients and animal models of CF similarly affected by various changes in the experimental set-up?". The review protocol was preregistered on PROSPERO (CRD42021236047). We searched PubMed and Embase with comprehensive search strings. Two independent reviewers screened all references for inclusion and extracted all data. Included were studies about CF which described in vivo nPD measurements in separate CF and control groups. Risk of bias was assessed, and three meta-analyses were performed. We included 130 references describing nPD values for CF and control subjects, which confirmed substantial variation in the experimental design and nPD outcome between groups. The meta-analyses showed a clear difference in baseline nPD values between CF and control subjects, both in animals and in humans. However, baseline nPD values were, on average, lower in animal than in human studies. Reporting of experimental details was poor for both animal and human studies, and urgently needs to improve to ensure reproducibility of experiments within and between species.

Animal to human translation: a systematic scoping review of reported concordance rates.

BACKGROUND: Drug development is currently hampered by high attrition rates; many developed treatments fail during clinical testing. Part of the attrition may be due to low animal-to-human translational success rates; so-called "translational failure". As far as we know, no systematic overview of published translational success rates exists. SYSTEMATIC SCOPING REVIEW: The following research question was examined: "What is the observed range of the animal-to-human translational success (and failure) rates within the currently available empirical evidence?". We searched PubMed and Embase on 16 October 2017. We included reviews and all other types of "umbrella"-studies of meta-data quantitatively comparing the translational results of studies including at least two species with one being human. We supplemented our database searches with additional strategies. All abstracts and full-text papers were screened by two independent reviewers. Our scoping review comprises 121 references, with various units of measurement: compound or intervention (k = 104), study/experiment (k = 10), and symptom or event (k = 7). Diagnostic statistics corresponded with binary and continuous definitions of successful translation. Binary definitions comprise percentages below twofold error, percentages accurately predicted, and predictive values. Quantitative definitions comprise correlation/regression (r2) and meta-analyses (percentage overlap of 95% confidence intervals). Translational success rates ranged from 0 to 100%. CONCLUSION: The wide range of translational success rates observed in our study might indicate that translational success is unpredictable; i.e. it might be unclear upfront if the results of primary animal studies will contribute to translational knowledge. However, the risk of bias of the included studies was high, and much of the included evidence is old, while newer models have become available. Therefore, the reliability of the cumulative evidence from current papers on this topic is insufficient. Further in-depth "umbrella"-studies of translational success rates are still warranted. These are needed to evaluate the probabilistic evidence for predictivity of animal studies for the human situation more reliably, and to determine which factors affect this process.

The use of fetal bovine serum: ethical or scientific problem?

Fetal bovine serum (FBS) is a common component of animal cell culture media. It is harvested from bovine fetuses taken from pregnant cows during slaughter. FBS is commonly harvested by means of a cardiac puncture without any form of anaesthesia. Fetuses are probably exposed to pain and/or discomfort, so the current practice of fetal blood harvesting is inhumane. Apart from moral concerns, several scientific and technical problems exist with regard to the use of FBS in cell culture. Efforts should be made to reduce the use of FBS or, preferably, to replace it with synthetic alternatives.