Use of connected digital products in clinical research following the COVID-19 pandemic: a comprehensive analysis of clinical trials

ObjectivesIn an effort to mitigate COVID-19 related challenges for clinical research, the US Food and Drug Administration (FDA) issued new guidance for the conduct of ‘virtual’ clinical trials in late March 2020. This study documents trends in the use of connected digital products (CDPs), tools that enable remote patient monitoring and telehealth consultation, in clinical trials both before and after the onset of the pandemic.DesignWe applied a comprehensive text search algorithm to clinical trial registry data to identify trials that use CDPs for remote monitoring or telehealth. We compared CDP use in the months before and after the issuance of FDA guidance facilitating virtual clinical trials.SettingAll trials registered on ClinicalTrials.gov with start dates from May 2019 through February 2021.Outcome measuresThe primary outcome measure was the overall percentage of CDP use in clinical trials started in the 10 months prior to the pandemic onset (May 2019–February 2020) compared with the 10 months following (May 2020–February 2021). Secondary outcome measures included CDP usage by trial type (interventional, observational), funder type (industry, non-industry) and diagnoses (COVID-19 or non-COVID-19 participants).ResultsCDP usage in clinical trials increased by only 1.65 percentage points, from 14.19% (n=23 473) of all trials initiated in the 10 months prior to the pandemic onset to 15.84% (n=26 009) of those started in the 10 months following (p<0.01). The increase occurred primarily in observational studies and non-industry funded trials and was driven entirely by CDP usage in trials for COVID-19.ConclusionsThese findings suggest that in the short-term, new options created by regulatory guidance to stimulate telehealth and remote monitoring were not widely incorporated into clinical research. In the months immediately following the pandemic onset, CDP adoption increased primarily in observational and non-industry funded studies where virtual protocols are likely medically necessary due to the participants’ COVID-19 diagnosis.

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Agreement of Primary Outcomes in Chiropractic-Related Clinical Trials Registered in clinicaltrials.gov with Corresponding Publication.

10.21203/rs.3.rs-48402/v1 ◽

2020 ◽

Author(s):

Robert Cote ◽

Stephen Perle ◽

Derek Martin

Keyword(s):

Clinical Trials ◽

Outcome Measures ◽

Primary Outcome ◽

A Priori ◽

Feasibility Studies ◽

Primary Outcome Measure ◽

Publication Rate ◽

Secondary Outcome ◽

Study Protocols ◽

Published Paper

Abstract Introduction:Previous analysis of registered clinical trials has found a disappointing number of study protocols result in publications which change what the registered a priori primary outcome measure is. Likewise, there is a disappointing rate of unpublished trials. Similar research has not been published on chiropractic-related studies. Primarily this investigation determined if reported primary outcomes in chiropractic-related clinical trials registered in clinicaltrials.gov match their published results. Secondarily, other outcome measures and publication status are assessed.Methodology:Clinicaltrials.gov was searched for chiropractic-related trials, using the search terms “chiropractic”, “chiropractor”, and having a completed status. Publication status was determined by searching PubMed (pubmed.gov), Index to Chiropractic Literature (chiroindex.org), and Google Scholar (scholar.google.com) through 29 May 2020. If the study was published, outcome measures were compared between the clinicaltrials.gov entry and the published paper to assess for consistency by two independent investigators. If there was disagreement between investigators, a third evaluated the data and decided if the published paper agreed with the clinicaltrials.gov entry.Results:Within clinicaltrials.gov 171 chiropractic-related protocols were identified. Twenty-five (25) had results posted and 102 were published. Twenty-nine of those entries produced multiple papers consisting of protocols, plot/feasibility studies, clinical trials, and poster presentations. Of the 102 studies published, 92 (90.2%) had agreement between their primary outcome and the listed entry on clinicaltrials.gov and 82 (80.4%) agreed with the secondary outcomes in the registered protocol. Entries on clinicaltrials.gov had a 59.6% (102/171) publication rate and a 14.6% (25/171) rate of displaying their results. Conclusion:A modest rate of agreement (90.2%) between clinicaltrails.gov entries and the 102 published papers (59.6% publication rate) were found. While chiropractic-related clinical trials are fewer in number compared to medical trials, chiropractic-related research has a substantially better rate of primary and secondary outcome concordance with registered protocols and a better publication rate. Investigators need to continue to upload results onto clinicaltrials.gov and seek publication regardless of the study findings. It is important to publish negative results so as not to introduce publication bias into systematic reviews and meta-analyses. Both positive and negative findings are important when evaluating treatments and determining the best care for patients.

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Calling for improved quality in the registration of traditional Chinese medicine during the public health emergency: a survey of trial registries for COVID-19, H1N1, and SARS

Trials ◽

10.1186/s13063-021-05113-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhuoran Kuang ◽

◽

Xiaoyan Li ◽

Jianxiong Cai ◽

Yaolong Chen ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Secondary Outcome ◽

Specific Information ◽

Clinical Trial Registry ◽

Data Set ◽

Diagnosis Criteria

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.

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Pulsed Shortwave Therapy in Cervical Osteoarthritis: an NSAID- Controlled, Randomized Clinical Trial

SN Comprehensive Clinical Medicine ◽

10.1007/s42399-020-00652-y ◽

2021 ◽

Author(s):

A. Rachid El Mohammad ◽

Sree Koneru ◽

Richard Staelin ◽

Kenneth McLeod ◽

Omar Tabbouche ◽

...

Keyword(s):

Adverse Effects ◽

Outcome Measures ◽

Neck Disability Index ◽

Primary Outcome Measure ◽

Pain Medication ◽

Secondary Outcome ◽

Pain Duration ◽

Cox 2 ◽

Neck Disability ◽

Pain At Rest

AbstractAssess treatment superiority of pulsed shortwave therapy (PSWT) against COX-2 NSAID therapy, in reducing disability and pain due to cervical osteoarthritis. Two hundred chronic pain suffers (average pain duration about 2 years) diagnosed with cervical osteoarthritis by radiological imaging were randomized into one of two treatment arms: COX-2 NSAID treatment; etoricoxib 60 mg/day for 4 weeks; or PSWT treatment worn 24 h/day for 4 weeks. The primary outcome measure was the 4-week score on the Neck Disability Index (NDI), a 10-question assessment on a 50-point scale. Secondary outcome measures included pain (at rest and during activity) measured on a visual analog scale (VAS) of 0–100 mm, dose count of rescue pain medication (paracetamol) use, and a treatment satisfaction rating. These 4-week scores were compared across the two arms to assess superiority. After 4 weeks of treatment, subjects in both study arms reported statistically significant (p < 0.0001) reductions in NDI, with final scores of 11.24-NSAID and 9.34-PSWT, VASrest, with final scores of 30.08-NSAID; 22.76-PSWT, and VASactivity, with final scores of 36.40-NSAID; 27.42-PSWT. The absolute reduction from baseline in NDI was significantly greater in the PSWT arm than NSAID arm (3.66 points; 95% CI 2.3 to 5.02; p < 0.0001). Similarly, the reductions from baseline in VASrest and VASactivity were significantly greater in the PSWT arm than NSAID arm (10.89 mm; 95% CI 6.90 to 14.87; p < 0.0001; and 12.05 mm; 95% CI 7.76 to 16.33; p < 0.0001, respectively). The PSWT arm used 50% less rescue pain medication. Eleven adverse effects were reported in the NSAID arm and zero in the PSWT arm. Both NSAID and PSWT treatments resulted in statistically significant improvements in quality of life (NDI) and reduction in pain (VAS) resulting from cervical osteoarthritis. However, the PSWT intervention showed superior improvements in all outcome measures when compared to the NSAID arm with no adverse effects. Clinicaltrials.gov (NCT03542955).

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Algorithm-Driven Pharmacological Management of Bipolar Disorder in Connecticut Prisons

International Journal of Offender Therapy and Comparative Criminology ◽

10.1177/0306624x11427537 ◽

2011 ◽

Vol 57 (2) ◽

pp. 251-264 ◽

Cited By ~ 6

Author(s):

Jayesh Kamath ◽

Wanli Zhang ◽

Karen Kesten ◽

Sara Wakai ◽

Deborah Shelton ◽

...

Keyword(s):

Bipolar Disorder ◽

Outcome Measures ◽

Clinical Status ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Type I ◽

Symptom Scale ◽

Pharmacological Management ◽

Correctional Setting ◽

Disorder Symptom

The objective of this study was to assess adaptation of the Texas Implementation of Medication Algorithm (TIMA) for bipolar disorder (BD) in the Connecticut Department of Correction. A nonrandomized sample of 20 males and 20 females, with diagnoses of BD Type I or II, was enrolled in the study. Two TIMA-trained psychiatrists treated the participants over a 12-week period following the TIMA protocol. The primary outcome measure was the Bipolar Disorder Symptom Scale. Secondary outcome measures evaluated global clinical status, comorbid symptomatology, and quality of life. Significant improvement was seen with the primary and secondary outcome measures ( p < .001). Subanalyses showed differences in outcomes based on gender and whether a manic or depression algorithm was used. Antidepressant and antipsychotic medication use decreased, with increase in anticonvulsant and anxiolytic medication usage. This pilot study confirmed the effectiveness and benefits of TIMA for BD adaptation in the correctional setting.

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Balloon Eustachian tuboplasty treatment of longstanding Eustachian tube dysfunction

The Journal of Laryngology & Otology ◽

10.1017/s0022215117000974 ◽

2017 ◽

Vol 131 (7) ◽

pp. 614-619 ◽

Cited By ~ 11

Author(s):

T Singh ◽

V Taneja ◽

K Kulendra ◽

M Farr ◽

J Robinson ◽

...

Keyword(s):

Outcome Measures ◽

Eustachian Tube ◽

Balloon Dilation ◽

Primary Outcome Measure ◽

Eustachian Tube Dysfunction ◽

Secondary Outcome ◽

Tube Dysfunction ◽

Previously Treated ◽

Objective Outcomes ◽

Balloon Eustachian Tuboplasty

AbstractBackground:Eustachian tube dysfunction is a poorly defined condition associated with various symptoms and it can predispose to middle-ear disease. Balloon dilation Eustachian tuboplasty has been proposed as a treatment for Eustachian tube dysfunction.Objective:To evaluate the subjective and objective outcomes of balloon dilation Eustachian tuboplasty in patients with recurrent, previously treated chronic Eustachian tube dysfunction.Methods:The study was conducted on 11 patients (13 ears) who had undergone previous unsuccessful medical and surgical treatment. Tympanometry was the primary outcome measure. Secondary outcome measures included pure tone audiogram assessment and seven-item Eustachian Tube Dysfunction Questionnaire score.Results:Balloon dilation Eustachian tuboplasty resulted in significant improvements in 11 patients’ subjective but not objective outcome measures.Conclusion:The objective abnormality and subjective symptoms in Eustachian tube dysfunction may represent two distinct pathological processes, which may nevertheless influence and exacerbate each other.

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Abatacept in the Treatment of Severe, Longstanding, and Refractory Uveitis Associated with Juvenile Idiopathic Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.140410 ◽

2015 ◽

Vol 42 (4) ◽

pp. 706-711 ◽

Cited By ~ 43

Author(s):

Christoph Tappeiner ◽

Elisabetta Miserocchi ◽

Bahram Bodaghi ◽

Kaisu Kotaniemi ◽

Friederike Mackensen ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Immunosuppressive Treatment ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Ocular Complications ◽

Systemic Corticosteroids ◽

Before And After ◽

Active Arthritis ◽

Factor Α ◽

Antigen Presenting

Objective.Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA).Methods.Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor–α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications.Results.In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup.Conclusion.A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

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Statistical analysis, trial design and duration in Alzheimer's disease clinical trials: a review

International Psychogeriatrics ◽

10.1017/s1041610211001116 ◽

2011 ◽

Vol 24 (5) ◽

pp. 689-697 ◽

Cited By ~ 17

Author(s):

P. A. Thompson ◽

D. E. Wright ◽

C. E. Counsell ◽

J. Zajicek

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Statistical Analysis ◽

Statistical Methods ◽

Outcome Measures ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure ◽

Primary Analysis

ABSTRACTBackground: The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate.Methods: We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol.Results: We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure.Conclusions: The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.

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Effects of Acupuncture on the Hypothalamus-Pituitary-Adrenal Axis in Chronic Insomnia Patients: A Study Protocol for a Randomized Controlled Trial

10.21203/rs.2.14637/v1 ◽

2019 ◽

Author(s):

Chengyong Liu ◽

Shiyu Zheng ◽

Wenzhong Wu ◽

Xiaoqiu Wang ◽

Shan Qin ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Outcome Measures ◽

Controlled Trial ◽

Severity Index ◽

Chronic Insomnia ◽

Secondary Outcome ◽

Therapeutic Effects ◽

Before And After ◽

Fatigue Severity

Abstract Background : Acupuncture, as an important component of traditional Chinese medicine (TCM), has been widely applied in the treatment of chronic insomnia in China，while there is no clinical study related to its therapeutic mechanism. Methods/design : A single-center, single-blind, randomized, placebo-controlled trial will be conducted at Jiangsu Hospital of Traditional Chinese Medicine. A total of 60 patients will be registered.Eligible participantswill be randomly divided into acupuncture group and shamacupuncture group (n = 30 cases in each group). Patients in both groups will be treated once every other day, 3 times per week for 4 weeks.The primary outcome measures are Pittsburgh Sleep Quality Index (PSQI), concentrations of adrenocorticotropic hormone (ATCH), Corticotrophin-releasing hormone (CRH), and cortisol (CORT). Secondary outcome measures are Insomnia Severity Index (ISI) and Fatigue Severity Scale (FSS). Discussion : This study aims to evaluate the therapeutic effects of acupuncture on chronic insomnia by using PSQI, ISI, and FSS. The mechanism of acupuncture on CIPs will be preliminarily discussed by analyzing the changes in concentrations of CRH, ACTH, and CORT before and after treatment.

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REiNS: Recommendations for Measurement of Attention Outcomes in Preschoolers With Neurofibromatosis

Neurology ◽

10.1212/wnl.0000000000012423 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012423

Author(s):

Bonita P. Klein-Tasman ◽

Kristin Lee ◽

Heather L. Thompson ◽

Jennifer Janusz ◽

Jonathan M. Payne ◽

...

Keyword(s):

Clinical Trials ◽

Rating Scale ◽

Dimensional Change ◽

Neurofibromatosis Type ◽

Primary Outcome Measure ◽

Attention Problems ◽

Developmental Trajectory ◽

Secondary Outcome ◽

Increased Risk ◽

Preschool Aged Children

Children with neurofibromatosis type 1 (NF1) are at increased risk for attention problems. While most research has been conducted with school-aged cohorts, preschool-aged children offer a novel developmental window for clinical studies, with the promise that treatments implemented earlier in the developmental trajectory may most effectively modify risk for later difficulties. Designing research studies around the youngest children with NF1 can result in intervention earlier in the developmental cascade associated with NF1 gene abnormalities. Furthermore, clinical trials for medications targeting physical and psychological aspects of NF1 often include individuals spanning a wide age range, including preschool-aged children. In a prior paper, the REiNS Neurocognitive Subcommittee made recommendations regarding performance-based and observer-rated measures of attention for use in clinical trials and highlighted the need for separate consideration of assessment methods for young children. The observer-rated ADHD Rating Scale – Preschool version is recommended as a primary outcome measure. The NIH Toolbox Flanker, Dimensional Change Card Sort, and List Sort Working Memory tasks and Digits Forward from the Differential Ability Scales – Second Edition (performance-based measures) are recommended as secondary outcome measures. Specific methodological recommendations for inclusion of preschoolers in clinical trials research are also offered.

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Combining Lovastatin and Minocycline for the Treatment of Fragile X Syndrome: Results From the LovaMiX Clinical Trial

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.762967 ◽

2022 ◽

Vol 12 ◽

Author(s):

Camille Champigny ◽

Florence Morin-Parent ◽

Laurence Bellehumeur-Lefebvre ◽

Artuela Çaku ◽

Jean-François Lepage ◽

...

Keyword(s):

Clinical Trial ◽

Fragile X Syndrome ◽

Outcome Measures ◽

Primary Outcome ◽

Outcome Measure ◽

Fragile X ◽

Combined Therapy ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Global Score

Background: Limited success of previous clinical trials for Fragile X syndrome (FXS) has led researchers to consider combining different drugs to correct the pleiotropic consequences caused by the absence of the Fragile X mental retardation protein (FMRP). Here, we report the results of the LovaMiX clinical trial, the first trial for FXS combining two disease-modifying drugs, lovastatin, and minocycline, which have both shown positive effects when used independently.Aim: The main goals of the study were to assess the safety and efficacy of a treatment combining lovastatin and minocycline for patients with FXS.Design: Pilot Phase II open-label clinical trial. Patients with a molecular diagnostic of FXS were first randomized to receive, in two-step titration either lovastatin or minocycline for 8 weeks, followed by dual treatment with lovastatin 40 mg and minocycline 100 mg for 2 weeks. Clinical assessments were performed at the beginning, after 8 weeks of monotherapy, and at week 20 (12 weeks of combined therapy).Outcome Measures: The primary outcome measure was the Aberrant Behavior Checklist-Community (ABC-C) global score. Secondary outcome measures included subscales of the FXS specific ABC-C (ABC-CFX), the Anxiety, Depression, and Mood Scale (ADAMS), the Social Responsiveness Scale (SRS), the Behavior Rating Inventory of Executive Functions (BRIEF), and the Vineland Adaptive Behavior Scale second edition (VABS-II).Results: Twenty-one individuals out of 22 completed the trial. There were no serious adverse events related to the use of either drugs alone or in combination, suggesting good tolerability and safety profile of the combined therapy. Significant improvement was noted on the primary outcome measure with a 40% decrease on ABC-C global score with the combined therapy. Several outcome measures also showed significance.Conclusion: The combination of lovastatin and minocycline is safe in patients for FXS individuals and appears to improve several elements of the behavior. These results set the stage for a larger, placebo-controlled double-blind clinical trial to confirm the beneficial effects of the combined therapy.

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