Developing Placebos for Clinical Research in Traditional Chinese Medicine: Assessing Organoleptic Properties of Three Dosage Forms (Oral Liquid, Capsule and Granule)

Background: The successful application of randomized, double-blind placebo-controlled studies requires maximum blinding. Organoleptic properties of the placebo should be similar to the drug, making it difficult to distinguish between the two. The uniqueness of traditional Chinese medicine (TCM) preparations makes it challenging to prepare placebo. Evaluation of the TCM placebo simulation effect can determine whether the preparation of placebo can be genuinely blind in clinical trials. There is still a lack of well-established methods to evaluate TCM placebos. Hence, this study aimed to explore the evaluation methodology of TCM placebo simulation.Methods: An independent evaluation method and three comparative evaluation methods were proposed, and three dosage forms (oral liquid, capsule, and granule) were tested. The independent evaluation, in which each person was given an experimental drug or a placebo, gave an overall assessment of organoleptic properties in a blind state. We comparatively evaluated the similarity in organoleptic properties between the experimental drug and placebo. According to different distribution methods, we divided comparative evaluation methods into three. In method 1, the evaluator was given the experimental drug and placebo and was told that there must be a placebo among them. In method 2, each evaluator was randomly assigned to the combination group or two investigational drugs group. In method 3, the evaluator was assigned to a set of three coded samples, numbered by random three-digit numbers, each different, two of which were identical, and the two samples were equally frequent.Results: In the independent evaluation, there was no difference between TCM placebo and experimental drugs in a blind state at the level of p = 0.05. Even though the comparative evaluation methods enabled identification of potential differences between the two samples, methods 2 and 3 were better than method 1 in eliminating psychological factors. Also, in method 3, the completely random method combined with the blind method eliminated the subjectivity and objectivity bias and improved the experiment’s credibility compared with the previous two methods.Conclusion: Regardless of the methods that could evaluate the placebo’s simulated effect in actual clinical trials, we suggest that independent evaluation and comparative evaluation (method 3) should be combined to reflect better whether the placebo is truly blind.

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Testing Meldonium: Assessing Soviet pragmatic alternatives to the randomized controlled trial

Clinical Trials ◽

10.1177/17407745211008540 ◽

2021 ◽

pp. 174077452110085

Author(s):

Anastasiya Chirkova ◽

Alexander Petrenko ◽

Pavel Vasilyev

Keyword(s):

Clinical Trials ◽

Randomized Controlled Trial ◽

Soviet Union ◽

Drug Testing ◽

Controlled Trial ◽

Randomized Controlled ◽

Experimental Drugs ◽

The Soviet Union ◽

Experimental Drug ◽

Second World

Background/aims Current research largely tends to ignore the drug-testing model that was developed in the “Second World” as an explicit alternative to the randomized controlled trial. This system can be described as “socialist pharmapolitics,” accounting for the specific features of state socialism that influenced the development and testing of experimental drugs. The clinical trials model employed in the “Second World” was heavily influenced by the Soviet Union, which was by far the most influential player in the socialist bloc during the Cold War. Based on extensive archival research, this article presents an empirical case of a late Soviet clinical trial as a pragmatic alternative to the randomized controlled trial model. It accounts for the divergences between the official model prescribed by the Soviet authorities and the messy realities of healthcare practice. It further outlines different factors that ultimately shaped how clinical trials were organized in Soviet institutions “on the ground.” Accordingly, this article presents a “real-life” history of “socialist pharmapolitics” and outlines the problems that this system faced in practice. Methods Archival research was conducted at the Russian State Archive of Scientific and Technical Documentation in Moscow. Archival files include scientific, technical, and registration documentation such as biochemical, pharmacological, and clinical descriptions of the experimental drug Meldonium, letters between various hospitals, research institutes and the Soviet regulatory body, as well as 26 reports of completed clinical trials. Manual content analysis was used for the interpretation of results. Results This article presents an empirical case of a late Soviet clinical trial as a pragmatic alternative to the randomized controlled trial model. It demonstrates some key differences from the randomized controlled trial model. This article also highlights some of the discrepancies between the model that was officially prescribed by the Soviet authorities and the realities of experimental drug testing in the Soviet Union in the late 1980s and early 1990s. In particular, it notes some elements of randomization, double-blinding, and the use of placebo that were present in Meldonium trials despite being formally denounced by Soviet bioethics. Conclusion The Soviet model for testing experimental drugs differed from the Western one substantially in a number of respects. This difference was not only proclaimed officially by the Soviet authorities, but was for the most part enforced in clinical trials in practice. At the same time, our research demonstrates that there were important differences between the official model and the clinical realities on the ground.

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Updated List of Light-Sensitive Oral Medications

Hospital Pharmacy ◽

10.1177/0018578719844699 ◽

2019 ◽

Vol 55 (6) ◽

pp. 349-365

Author(s):

Scott Perkins ◽

Adam Evans ◽

Allison King

Keyword(s):

Dosage Form ◽

Drug Information ◽

Dosage Forms ◽

Drug Products ◽

Solid Dosage ◽

Oral Medications ◽

Information Center ◽

Oral Liquid ◽

Liquid Products ◽

Professional Resources

The Campbell University Drug Information Center supports health professionals by providing responses to drug-related inquiries. An inquiry was received by the Drug Information Center for a comprehensive list of oral solutions which should be protected from light. In investigating this request for information, a list of light-sensitive oral prescription drug products published in Hospital Pharmacy in 2009 was identified. This discovery highlighted the need for both an updated list and one which distinguished oral solid products and oral liquid products. The purpose of this project was to update the previously published list and to distinguish between oral solid and liquid dosage forms. The process of updating this list entailed several professional resources. A list of all oral products was obtained and then sorted to clearly identify which products were available in oral solid dosage form only, oral liquid dosage form only, and both dosage forms. Once delineated, the product labels for each medication were scoured for language indicating the product is light sensitive.

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Research and Evaluation of Bionics Shape Design Based on Cases

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.551.621 ◽

2014 ◽

Vol 551 ◽

pp. 621-625

Author(s):

Nan Chu Guo

Keyword(s):

Genetic Algorithm ◽

Quantitative Methods ◽

Evaluation Method ◽

Evaluation Methods ◽

Shape Design ◽

Fuzzy Evaluation ◽

Ideal Approach ◽

Comprehensive Fuzzy Evaluation

The paper proposes an ideal approach of shape design by using shape evaluation methods accurately. The paper proposes and tests the comprehensive fuzzy evaluation method using a case of two clips based on genetic algorithm and quantitative methods. By using this evaluation method, the shape details of a product could be improved gradually.

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Based on the Fuzzy Multi-Objective People Decision Method of Engineering Bidding Evaluation

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.671-674.3147 ◽

2013 ◽

Vol 671-674 ◽

pp. 3147-3151

Author(s):

Yun Na Wu ◽

Chao Liu ◽

Mandula Naren ◽

He Ping Wang ◽

Jian Chen

Keyword(s):

Evaluation Method ◽

Comprehensive Evaluation ◽

Evaluation Methods ◽

Actual Case ◽

Engineering Construction ◽

Comprehensive Evaluation Method ◽

Multi Objective ◽

Bidding Price ◽

Weight Method ◽

Conducting Research

The construction project bidding is a feasible method in engineering transactions and the main competition form of the construction activities under the conditions of the market economy. The bid assessment is an important link of bidding, and whether bid evaluation method is scientific or not, is directly related to the success of the tender. In the engineering construction field, at present the current commonly used evaluation methods are the comprehensive evaluation method and the lowest bidding price evaluation method. Based on fuzzy set theory and multi-objective people decision theory, we introduce fuzzy multi-objective people decision-making evaluation methods. And conducting research to put forward the evaluation index and weight method to determine the bidding decision model. Finally we apply it to actual case to make out the more standardized and scientific bidding evaluation method.

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Use of a placebo in clinical trials

European Psychiatry ◽

10.1016/s0924-9338(98)80031-x ◽

1998 ◽

Vol 13 (5) ◽

pp. 254-263 ◽

Cited By ~ 2

Author(s):

G Emilien ◽

JM Maloteaux ◽

A Seghers ◽

G Charles

Keyword(s):

Clinical Trials ◽

Placebo Response ◽

Drug Efficacy ◽

Placebo Treatment ◽

High Response Rate ◽

Experimental Methodology ◽

Necessary Condition ◽

Control Group ◽

Placebo Control ◽

Experimental Drug

SummaryThe use of a placebo control group in the evaluation of a new product is today considered by most as a necessary condition of experimental drug research. Placebo response is an essential consideration in all clinical trials. If not properly controlled, incorrect and dangerous conclusion may be inferred for a product efficacy and safety profile. However, the inclusion of a placebo group in clinical trials in neuropsychiatric research raises several ethical and scientific questions. Whereas in certain indications, such as suicidal patients and severe and psychotic depression, the use of a placebo is generally not accepted, it is difficult to assess drug efficacy. This article discusses the concept of placebo in clinical trials, the occurrence of adverse events after placebo treatment and the high response rate of placebo in neuropsychiatric clinical research. The experimental methodology to adequately control all the factors involved is also analysed and discussed.

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Study on Defogging Effect Evaluation Method in Atomization Image

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.672-674.1972 ◽

2014 ◽

Vol 672-674 ◽

pp. 1972-1976

Author(s):

Zhen Chen ◽

Fan Wu

Keyword(s):

Evaluation Method ◽

Evaluation Methods ◽

Image Contrast ◽

Effect Evaluation ◽

Edge Structure ◽

Evaluation Result ◽

Relative Contrast ◽

Overall Evaluation ◽

Edge Similarity ◽

Human Eyes

For the problems of few current defogging effect evaluation methods and limited evaluation methods, it proposes an image clarity effect evaluation method: the method combined with relative contrast and edge similarity. This is because: the contrast degree of fog image and non-fog image is obviously different. While improving image contrast degree, it should also try to make the edge structure of recovery image and reduced image consistent to prevent the recovery image from distorting. The experiment proves that this method can effectively evaluate the clarity effect of each algorithm, and the evaluation result and the subjective feelings of the human eyes are consistent. Compared with the existing evaluation methods, it obtains overall evaluation conclusion and also has a good practicability and reliability.

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A Corpus Based Method for Evaluating the Teaching Effect of Electronic Engineering English

Tobacco Regulatory Science ◽

10.18001/trs.7.5.39 ◽

2021 ◽

Vol 7 (5) ◽

pp. 1222-1229

Author(s):

Yong LIU

Keyword(s):

Quantitative Analysis ◽

Evaluation Method ◽

Evaluation Model ◽

Evaluation Methods ◽

Effect Evaluation ◽

Application Performance ◽

English Teaching ◽

Electronic Engineering ◽

Quantitative Analysis Method ◽

Standard Value

The existing evaluation methods have the problem of imperfect teaching effect evaluation model, which leads to the low reliability of the evaluation index. This paper designs a corpus based quantitative analysis method for teaching effect evaluation of Electronic Engineering English. Based on the mathematical principle of radial basis function, this paper uses corpus to analyze the distribution characteristics of Electronic Engineering English courses quantitatively, and uses association rules algorithm to build an English teaching effect evaluation model to comprehensively judge the importance of each factor. Experimental results: the average reliability of the two existing evaluation methods is 1.0751 and 0.5455 respectively, and the average reliability of the evaluation method is 0.7983, which shows that the reliability of the evaluation method is closer to the standard value of 0.8, which proves that the evaluation method of Electronic Engineering English teaching effect integrated with quantitative analysis of corpus has better practical application performance good.

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PP126 MEA In Italy: Correlation Between Time To Payment By Result And Time To Off Treatment Curve

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462317002811 ◽

2017 ◽

Vol 33 (S1) ◽

pp. 131-132

Author(s):

Gabriele Vittoria ◽

Antonio Fascì ◽

Matteo Ferrario ◽

Giovanni Giuliani

Keyword(s):

Clinical Trials ◽

Treatment Failure ◽

Median Time ◽

Real Life ◽

Standard Of Care ◽

Phase Iii ◽

Experimental Drug ◽

The Mean ◽

Line Of Therapy ◽

Mean Time

INTRODUCTION:Payment by result agreements have been quite widely used in Italy to provide access for high costs oncologic drugs and minimize uncertainties of real life benefits (1). The aim of this analysis was to overview the Roche experience in terms of Payment by Result (Pbr) in oncology and investigate the relation between timing for the evaluation of treatment failures and observed Time to Off Treatment (TTOT) from Phase III clinical trials (2).METHODS:A retrospective analysis of the Roche payment by results schemes in place in Italy was conducted. For each drug included in the analysis it was collected: (i) the negotiated timing to assess the treatment failure for payment by result, (ii) the median time to off treatment curve observed in clinical trials for the experimental drug, (iii) the median time to off treatment observed in clinical trials for the control arm. The mean ratios between timing to assess the treatment failure for payment by result and the time to off treatment observed for the experimental drug or the median time to off treatment observed in the control arm were calculated to identify potential correlations. High level of correlation was expected if ratio was close to 1 (±.2).RESULTS:Roche products or different indications of the same product were identified as candidates for the analysis from 2008 to 2016. The timing for the evaluation of treatment failures for Pbr varies between 2 and 9 months, depending on the type of tumor and line of therapy. The mean Time to Payment By Result (TTPbr) / Control arm Time To Off Treatment (cTTOT) ratio was 1.16 (±.37) while the mean Time to Payment By Result (TTPbr) / Experimental arm Time To Off Treatment (eTTOT) ratio was .71 (±.13). Data analysis according to different time periods shows that the mean TTPbr/cTTOT and TTPbr/eTTOT for drugs negotiated from 2008 to 2015 were respectively 1.07 and 1.39 whereas for drugs negotiated in 2016 were respectively and .63 and 1.CONCLUSIONS:Good level of correlation between TTPbr and cTTOT was found. This finding is in line with the methodology used by Italian Medicines Agency so far, leveraging the cTTOT as the most appropriate proxy to assess any incremental effect of a new drug compared to the previous Standard of Care. The analysis over time of TTPbr shows that in the first years of payment by result negotiation TTPbr is more correlated to the cTTOT whereas in the last years is moving closer to the experimental one.

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