Design of Control-Group Conditions in Clinical Trials of Behavioral Interventions

Behavioral interventions involving electronic devices, financial incentives, gamification, and specially trained staff to encourage healthy behaviors are becoming increasingly prevalent and important in health innovation and improvement efforts. Although considerations of cost are key to their wider adoption, cost information is lacking because the resources required cannot be costed using standard administrative billing data. Pragmatic clinical trials that test behavioral interventions are potentially the best and often only source of cost information but rarely incorporate costing studies. This article provides a guide for researchers to help them collect and analyze, during the trial and with little additional effort, the information needed to inform potential adopters of the costs of adopting a behavioral intervention. A key challenge in using trial data is the separation of implementation costs, the costs an adopter would incur, from research costs. Based on experience with 3 randomized clinical trials of behavioral interventions, this article explains how to frame the costing problem, including how to think about costs associated with the control group, and describes methods for collecting data on individual costs: specifications for costing a technology platform that supports the specialized functions required, how to set up a time log to collect data on the time staff spend on implementation, and issues in getting data on device, overhead, and financial incentive costs.

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Personalized Behavioral Nutrition Intervention in Older Asian Americans with Type 2 Diabetes during COVID-19 Pandemic: Study Protocol for a Pilot, Hybrid, Randomized Controlled Trial (Preprint)

10.2196/preprints.23522 ◽

2020 ◽

Author(s):

Jisook Ko ◽

Yan Du ◽

Rozmin Jiwani ◽

Chengdong Li ◽

Jing Wang

Keyword(s):

Type 2 Diabetes ◽

Clinical Trials ◽

Pilot Study ◽

Glycemic Control ◽

Asian Americans ◽

Control Group ◽

Management Approach ◽

Self Monitoring ◽

Behavioral Nutrition

BACKGROUND The COVID-19 pandemic has challenged the in-person-based self-management approach (i.e., face-to-face or group approach) of type 2 diabetes (T2D). Older adults with T2D, including Asian Americans (AAs), have experienced worsening of diabetes control due to various reasons, including uncertainty of continuous access to essential diabetes medications, devices, education, limited health literacy, as well as constant anxiety and stress. Hybrid clinical trials that incorporate virtual elements into the in-person-based study could provide these vulnerable populations with accessible and timely interventions OBJECTIVE The primary aims of this pilot study are to determine (1) the effect of personalized behavioral nutrition (PBN) intervention on glycemic control, weight control, and metabolites profiles; and (2) the acceptability of PBN. to enhance glycemic control using personalized behavioral nutrition. METHODS Participants will be recruited with a web-based registry, advertisements in ethnic newspapers, and social network services popular among AAs. A total of 60 AAs, aged 65 years or older, who are descendants of Chinese, Korean, or South Asian, and have a diagnosis of T2D will be randomized into two groups: a PBN group (n=30) and a control group (n=30). A 4-week PBN intervention comprises three components: 1) digital self-monitoring; 2) personal nutrition change goals and recommendations; and 3) diabetes nutrition educations. All participants will complete digital self-monitoring on diet, physical activity, and blood glucose. In addition, all participants will access an interactive digital platform to track their self-monitoring data and communicate with the research team. The effectiveness and acceptability of implementing the intervention will be assessed. RESULTS Funding support and institutional review board approval for this study have been secured. Data collection started in August 2020 and is ongoing. CONCLUSIONS To our knowledge, this is the first study to determine the effectiveness and acceptability of PBN utilizing a metabolomics approach and digital-assisted intervention with hybrid RCT among older AAs. The findings of this pilot study will inform the development of a full-scale PBN protocol and hybrid clinical trials that can be adapted for people with T2D in the ongoing pandemic.

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Effect of Tai Chi Training on Plantar Loads during Walking in Individuals with Knee Osteoarthritis

BioMed Research International ◽

10.1155/2020/3096237 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Zhiwang Zhang ◽

Lingyan Huang ◽

Yu Liu ◽

Lin Wang

Keyword(s):

Clinical Trials ◽

Knee Osteoarthritis ◽

Education Program ◽

Tai Chi ◽

Peak Pressure ◽

Maximum Force ◽

Control Group ◽

Link Type ◽

Wellness Education ◽

Metatarsophalangeal Joints

Tai Chi is an available method for the treatment of knee osteoarthritis (KOA). The impacts of Tai Chi on plantar loads of individuals with KOA are not fully understood. 46 participants with knee osteoarthritis were randomly assigned into the Tai Chi group (n=23) or the control group (n=23). The Tai Chi group attended a 6-month Tai Chi program, and the control group participated in a wellness education program. Novel Pedar-X system was used to collect the peak pressure (PP) and maximum force (MF) during walking before and 6 months after the intervention. Significant higher peak pressure and maximum force were observed in the 4th and 5th metatarsophalangeal joints in the Tai Chi group. However, there were significant declines in the peak pressure of the whole foot and the 2nd and 3rd metatarsophalangeal joints and maximum force of the heel in the control group. These results suggested that individuals with KOA might change the pattern of plantar loads during walking through Tai Chi, and plantar loads would be useful as a parameter to assess the effect of Tai Chi on knee osteoarthritis. This trial is registered with Clinical Trials: CHiCTR-TRC-13003264.

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AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

Cell Death and Disease ◽

10.1038/s41419-021-03546-6 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Sipin Zhu ◽

Yibo Ying ◽

Jiahui Ye ◽

Min Chen ◽

Qiuji Wu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Trials ◽

Control Group ◽

Therapeutic Effects ◽

Hypoxia Response Element ◽

Neurofilament Protein ◽

Response Element ◽

Hypoxia Response ◽

Cord Injury

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.

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DigiKnowIt News: Educating youth about pediatric clinical trials using an interactive, multimedia educational website

Journal of Child Health Care ◽

10.1177/13674935211003774 ◽

2021 ◽

pp. 136749352110037

Author(s):

Alison E. Parker ◽

Tracy M. Scull ◽

Abigail M. Morrison

Keyword(s):

Clinical Trials ◽

Interactive Multimedia ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

Wait List ◽

Wait List Control Group ◽

Wait List Control ◽

Satisfaction Questionnaire ◽

Study Participants

Pediatric clinical trials allow for the testing of appropriate and effective treatments for children. However, some challenges exist with recruitment. This study examined the effectiveness of DigiKnowIt News, an interactive, multimedia website (which includes activities, videos, and comic books) designed to educate children about clinical trials. A randomized controlled trial was conducted in 2018 with 91 participants ( M age = 10.92 years; SD = 2.06). Participants were randomly assigned to intervention or wait-list control groups and completed questionnaires at pretest and posttest (1 week later) about their knowledge, attitudes, beliefs about clinical trials, and self-efficacy for participating in clinical trials. Participants in the intervention group received access to DigiKnowIt News between pretest and posttest and completed a satisfaction questionnaire at posttest. At the end of the study, participants in the wait-list control group were offered the option to use the website and complete a satisfaction questionnaire. At posttest, participants in the intervention group, compared to participants in the wait-list control group, had more knowledge about clinical trials and more reported confidence for participating in clinical trials. Participants reported high levels of satisfaction with DigiKnowIt News. The findings suggest that an educational website can improve factors related to increasing rates of participation in clinical trials.

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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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Comparative Effects of Physical Exercise and Other Behavioral Interventions on Functional Status Outcomes in Mild Cognitive Impairment

Journal of the International Neuropsychological Society ◽

10.1017/s1355617721000485 ◽

2021 ◽

pp. 1-8

Author(s):

Anne L. Shandera-Ochsner ◽

Melanie J. Chandler ◽

Dona E. Locke ◽

Colleen T. Ball ◽

Julia E. Crook ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Physical Exercise ◽

Behavioral Interventions ◽

Functional Decline ◽

Well Being ◽

Control Group ◽

Lifestyle Modifications ◽

Clinical Dementia Rating ◽

Group Sessions

Abstract Objectives: Lifestyle modifications for those with mild cognitive impairment (MCI) may promote functional stability, lesson disease severity, and improve well-being outcomes such as quality of life. The current analysis of our larger comparative effectiveness study evaluated which specific combinations of lifestyle modifications offered as part of the Mayo Clinic Healthy Action to Benefit Independence in Thinking (HABIT) program contributed to the least functional decline in people with MCI (pwMCI) over 18 months. Methods: We undertook to compare evidence-based interventions with one another rather than to a no-treatment control group. The interventions were five behavioral treatments: computerized cognitive training (CCT), yoga, Memory Support System (MSS) training, peer support group (SG), and wellness education (WE), each delivered to both pwMCI and care partners, in a group-based program. To compare interventions, we randomly withheld one of the five HABIT® interventions in each of the group sessions. We conducted 24 group sessions with between 8 and 20 pwMCI–partner dyads in a session. Results: Withholding yoga led to the greatest declines in functional ability as measured by the Functional Activities Questionnaire and Clinical Dementia Rating. In addition, memory compensation (calendar) training and cognitive exercise appeared to have associations (moderate effect sizes) with better functional outcomes. Withholding SG or WE appeared to have little effect on functioning at 18 months. Conclusions: Overall, these results add to the growing literature that physical exercise can play a significant and lasting role in modifying outcomes in a host of medical conditions, including neurodegenerative diseases.

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Parkinson's disease and convergence insufficiency: a mini-review

Medical Hypothesis, Discovery & Innovation in Optometry ◽

10.51329/mehdioptometry114 ◽

2021 ◽

Vol 1 (3) ◽

pp. 108-111

Author(s):

Mashael Al-Namaeh

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Trials ◽

Control Group ◽

Healthy Controls ◽

Inclusion Criteria ◽

Medline Search ◽

Convergence Insufficiency ◽

Eye Examination ◽

The Relationship

Background: A key manifestation of Parkinson’s disease (PD) is visual impairment. Cognitive impairment has been found to overlap with convergence insufficiency (CI) in patients with PD and is associated with significantly greater near point convergence (NPC) distance. Difficulty in reading and diplopia were the most common symptoms of CI in PD. The prevalence of CI is greater among patients with PD. Therefore, this study aimed to assess the relationship between PD and CI. Methods: Studies that had included data on CI, NPC, or both were selected by searching PubMed/MEDLINE and clinicaltrails.gov, without any timeline or language limitation. The following terms were used in PubMed/MEDLINE search: ‘Clinical Trials’, ‘Parkinson’s Disease’, and ‘Convergence Insufficiency’. For clinical trials.gov database, the terms ‘Parkinson’s Disease’, ‘Convergence Insufficiency’, and ‘Completed Studies’ were used. Only those studies with control subjects were included. PubMed/MEDLINE search yielded 1,563 articles, but no article was found in the clinical trails.gov search. Twelve articles met the inclusion criteria, among which nine articles were selected as they had data on CI or NPC distance (cm), and PD. Results: Overall, there were 1,563 articles; among them, 12 articles met the inclusion criteria. Nine articles were selected based on their data concerning CI or NPC distance (cm) and PD. Relative to the control group, the PD group had high CI. In addition, PD group showed increase in NPC distance than the control group. Conclusions: These data suggest that the patients with PD had an increased likelihood of developing CI visual symptoms, and increased NPC distance than healthy controls. These findings indicate that regular eye examination is very important for patients with PD.

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Melatonin reduces the mortality of severely-infected COVID-19 patients

Melatonin Research ◽

10.32794/mr112500115 ◽

2021 ◽

Vol 4 (4) ◽

pp. 613-616

Author(s):

Dun-Xian Tan ◽

Russel J Reiter

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Mortality Rate ◽

Randomized Clinical Trial ◽

Control Group ◽

Mortality Reduction ◽

Single Center ◽

Open Label ◽

Melatonin Treatment ◽

The World

SARS-CoV-2 has ravaged the population of the world for two years. Scientists have not yet identified an effective therapy to reduce the mortality of severe COVID-19 patients. In a single-center, open-label, randomized clinical trial, it was observed that melatonin treatment lowered the mortality rate by 93% in severely-infected COVID-19 patients compared with the control group (see below). This is seemingly the first report to show such a huge mortality reduction in severe COVID-19 infected individuals with a simple treatment. If this observation is confirmed by more rigorous clinical trials, melatonin could become an important weapon to combat this pandemic.

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A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/2163053 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 10

Author(s):

Liang Song ◽

Meng-Bei Xu ◽

Xiao-Li Zhou ◽

Dao-pei Zhang ◽

Shu-ling Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Trials ◽

Quality Score ◽

Control Group ◽

Rotarod Test ◽

Neuroprotective Effects ◽

Disease Modifying ◽

Antioxidant Stress ◽

Th Mrna

To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson’s disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P<0.01), two studies for improving the swim-score values (P<0.01), six studies for improving the level of TH protein expression (P<0.01), and two studies for increasing the expression of TH mRNA in the substantia nigra of mice (P<0.01). The studies reported that G-Rg1 exerted potential neuroprotective effects on PD model through different mechanisms as antineuroinflammatory activities (n=10), antioxidant stress (n=3), and antiapoptosis (n=11). In conclusion, G-Rg1 exerted potential neuroprotective functions against PD largely by antineuroinflammatory, antioxidative, and antiapoptotic effects. G-Rg1 as a promising neuroprotectant for PD needs further confirmation by clinical trials.

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