scholarly journals ‘Statistical Irreproducibility’ Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research

2021 ◽  
Vol 11 (3) ◽  
pp. 234
Author(s):  
Abigail R. Basson ◽  
Fabio Cominelli ◽  
Alexander Rodriguez-Palacios

Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the ‘reproducibility of statistical results or direction of the effects’. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person–person differences and personalized medicine.

1990 ◽  
Vol 29 (03) ◽  
pp. 243-246 ◽  
Author(s):  
M. A. A. Moussa

AbstractVarious approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns.


2018 ◽  
Vol 5 (2) ◽  
pp. 13-20
Author(s):  
Lia Kamila ◽  
Liawati . ◽  
Suci Lailani Alipah

ABSTRAK Indikator D/S di wilayah kerja Puskesmas Saguling Desa Cipangeran pada tahun 2016 menunjukkan masih rendahnya kunjungan balita dalam kegiatan posyandu dengan rata-rata hanya memcapai 41,5%, sedangkan target standar palayanan kota jumlah D/S yaitu 85%. Tujuan penelitian ini adalah untuk mengetahui keteraturan ibu dalam mengunjungi Posyandu dari faktor pengetahuan di Desa Cipangeran Kecamatan Saguling Kabupaten Bandung Barat tahun 2017. Metode penelitian ini menggunakan metode analitik dengan pendekatan cross sectional. Data yang digunakan adalah data primer. Populasi seluruh balita di wilayah kerja Puskesmas Saguling tahun 2016 sebanyak 424 ibu balita, besar sampel yang diambil 81 ibu balita, pengambilan sampel dengan menggunakan Sampel Random Sampling, pengumpulan data dengan hasil kuesioner berisi pertanyaan untuk mendapatkan data yang berkaitan dengan variabel yang diteliti. Hasil penelitian pengetahuan ibu balita didapatkan hampir setengah berada dikategori cukup yaitu 47 ibu balita (58%), namun masih ada ibu balita yang memiliki pengetahuan baik yaitu 18 ibu balita (22%), dan ibu balita yang memiliki pengetahuan kurang yaitu 16 ibu balita (20%). Kesimpulan dari penelitian didapatkan tingkat pengetahuan ibu balita yang tidak teratur dalam mengunjungi Posyandu di Desa Cipangeran Kecamatan Saguling Kabupaten Bandug Barat hampir setengah ibu balita berpengetahuan cukup. ABSTRACT The D / S indicator in the working area of ​​Saguling Public Health Center of Cipangeran Village in 2016 indicates that the low number of toddler visits in posyandu activities reaches an average of 41.5%, while the standard target for city / city is 85%. The purpose of this study is to determine the regularity of mothers in visiting Posyandu from knowledge factor in Cipangeran Village, Saguling District, West Bandung regency in 2017. This research method using analytical method with cross sectional approach. The data used is primary data.The population of all toddlers in the working area of Saguling Publich Health Center in 2016 were 424 mother, the sample size was 81 mother, using Random Sampling , data collection with questionnaires containing questions to obtain data related to the variables studied. The result of the research of the knowledge of the mother of the toddler is almost sufficient, namely 47 mothers (58%),but there are still mother who have good knowledge that is 18 mother of toddler (22%) and mother with less knowledge that is 16 mother of balita (20%). The conclusion of the research is the level of knowledge of irregular mother in visiting Posyandu in Cipangeran Village, Saguling, of West Bandung district, almost half of the toddler are knowledgeable enough.


2020 ◽  
Vol 26 (2) ◽  
pp. 218-227
Author(s):  
Yi-Hang Chiu ◽  
Chia-Yueh Hsu ◽  
Mong-Liang Lu ◽  
Chun-Hsin Chen

Background: Clozapine has been used in treatment-resistant patients with schizophrenia. However, only 40% of patients with treatment-resistant schizophrenia have response to clozapine. Many augmentation strategies have been proposed to treat those clozapine-resistant patients, but the results are inconclusive. In this review, we intended to review papers dealing with the augmentation strategies in the treatment of clozapineresistant patients with schizophrenia. Method: We reviewed randomized, double-blind, placebo- or sham-controlled trials (RCT) for clozapine-resistant patients with schizophrenia in Embase, PsycINFO, Cochrane, and PubMed database from January 1990 to June 2019. Results: Antipsychotics, antidepressants, mood stabilizers, brain stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation, and other strategies, were used as an augmentation in clozapine-resistant patients with schizophrenia. Except for better evidence in memantine with 2 RCTs and cognitive behavior therapy in 2 studies to support its effectiveness, we found that all the other effective augmentations, including sulpiride, ziprasidone, duloxetine, mirtazapine, ECT, sodium benzoate, ginkgo biloba, and minocycline, had only one RCT with limited sample size. Conclusion: In this review, no definite effective augmentation strategy was found for clozapine-resistant patients. Some potential strategies with beneficial effects on psychopathology need further studies with a larger sample size to support their efficacy.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Rubayet Elahi ◽  
Ausraful Islam ◽  
Mohammad Sharif Hossain ◽  
Khaja Mohiuddin ◽  
Andrea Mikolon ◽  
...  

The parasites of generaHaemoproteus, Plasmodium,andLeucocytozoonare well-known avian haematozoa and can cause declined productivity and high mortality in wild birds. The objective of the study was to record the prevalence of haematozoan parasites in a wide range of wetland birds in Bangladesh. Six species ofHaemoproteus, seven species ofPlasmodium, one unidentified species ofLeucocytozoon, and one unidentified microfilaria of the genusParonchocercawere found. Data on the morphology, size, hosts, prevalence, and infection intensity of the parasites are provided. The overall prevalence among the birds was 29.5% (95 out of 322 birds). Of those, 13.2% (42 of 319) of birds were infected withHaemoproteusspp., 15.1% withPlasmodiumspp. (48 of 319) and 0.6% withLeucocytozoonspp. (2 of 319). Two birds were positive for bothHaemoproteussp. andPlasmodiumsp. A single resident bird,Ardeola grayii, was found positive for an unidentified microfilaria. Prevalence of infection varied significantly among different bird families. Wild birds of Bangladesh carry several types of haematozoan parasites. Further investigation with a larger sample size is necessary to estimate more accurately the prevalence of haematozoan parasites among wild birds as well as domestic ducks for better understanding of the disease ecology.


2020 ◽  
Vol 30 (1) ◽  
pp. e38066
Author(s):  
Jimmie Leppink

Research in education is often associated with comparing group averages and linear relations in sufficiently large samples and evidence-based practice is about using the outcomes of that research in the practice of education. However, there are questions that are important for the practice of education that cannot really be addressed by comparisons of group averages and linear relations, no matter how large the samples. Besides, different types of constraints including logistic, financial, and ethical ones may make larger-sample research unfeasible or at least questionable. What has remained less known in many fields is that there are study designs and statistical methods for research involving small samples or even individuals that allow us to address questions of importance for the practice of education. This article discusses one type of such situations and provides a simple coherent statistical approach that provides point and interval estimates of differences of interest regardless of the type of the outcome variable and that is of use in other types of studies involving large samples, small samples, and single individuals.


Author(s):  
Nehad J. Ahmed

Aims: This study aims to review the efficacy of chloroquine and hydroxychloroquine to treat coronavirus disease 2019 (COVID-19) associated pneumonia. Methodology: This review includes searching Google scholar for publications about the use of hydroxychloroquinein the treatment of COVID-19 using the words of (Covid-19) AND hydroxychloroquine. Results: Chloroquine and hydroxychloroquine have proven effective in treating coronavirus in China in vitro, but till now only few clinical trials are available and these trials were conducted on a small sample size of the patients. The efficacy of chloroquine and hydroxychloroquine is mainly due to its effect on angiotensin-converting enzyme II (ACE2). Conclusion: The use of chloroquine and hydroxychloroquine could be very promising but more trials are needed that include larger sample size and more data are required about the comparison between chloroquine and hydroxychloroquine with other antivirals.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Maarten G Lansberg ◽  
Robin Lemmens ◽  
Soren Christensen ◽  
Nishant K Mishra ◽  
Gregory W Albers

Background: Recent trials have shown no benefit of endovascular therapy. This may, in part, be explained by inaccurate estimates of the treatment effect used in the sample size calculations of these trials. A predictive model which includes variables that modify the expected treatment effect might yield more accurate estimates, and could be valuable in the design of future acute stroke trials. Methods: We conducted a literature review to obtain estimates of parameters that are associated with good functional outcome (GFO) following recanalization. We developed a model to estimate the treatment effect in endovascular stroke trials and applied this model to two recently published endovascular stroke trials. Results: We estimated a 40% absolute difference in the proportion of GFO (mRS 0-2 at 90 days) associated with reperfusion in patients with ICA or M1 occlusions who have a substantial ischemic penumbra at baseline. To estimate the effect size in trials, this value was multiplied by: 1) the proportion of patients undergoing endovascular therapy in the active treatment arm; 2) the proportion of patients with occlusions of the ICA or MCA-M1; 3) the proportion of patients with a substantial penumbra and a DWI lesion <50mL; and 4) the absolute difference in the proportion of patients with reperfusion, defined as TICI 2B-3, between the endovascular treatment and control arms. Based on literature review we assumed a reperfusion rate of 20% in the control arms of IMS III and MR Rescue, a 50% prevalence of patients with substantial penumbra and DWI lesions<50 mL in IMS III, and a 75% prevalence in the penumbral arms of MR Rescue. Based on these model inputs, a 2.2% increase in GFO with endovascular therapy was expected in IMS III, which closely matches the observed 2.1% increase. For MR Rescue, the model predicted a 1.5% increase in GFO with endovascular therapy. Considering the small sample size, this equates to 0.5 additional patients with GFO which closely matches the observed result of 3 fewer patients with GFO. Conclusion: A simple model shows promise for estimating the treatment effect of endovascular stroke trials. It may be useful for the design of future trials and could lead to different inclusion criteria or larger sample sizes compared to the recently conducted studies.


1972 ◽  
Vol 55 (1) ◽  
pp. 173-176
Author(s):  
Edward Smith ◽  
Eric B Sheixix ◽  
Joseph Levixe

Abstract The current AOAC method for the determination of morphine in opium, 36.031–36.035, utilizes a 3-column partition chromatographic system for the isolation of morphine, with spectrophotometric measurement of the product. The same partition system has been modified to accommodate a larger sample size to permit a gravimetric measurement of the isolated morphine as its dinitrophenyl ether. The gravimetric procedure yields values comparable to those obtained by the much shorter and simpler UV method.


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