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Sample size calculation
G* Power was used to conduct an a-priori sample size calculation. Based on previous research [
PMC10508026
Results
Due to participant drop-out and failed attention checks, N = 1126 participants (94% of intended sample) were included in the final sample for analyses. See Fig.  Participant characteristics overall, and across the four conditionsCategorical variables are represented by counts/percentages, and continuous variables by me...
PMC10508026
Primary analyses
PMC10508026
Food orders
Mean orders for the four conditions are presented fully in Supplementary material VIII. Data of size choice are visually represented in Fig.  The proportion of participants opting for a larger size option for all three outlets across the four conditions
PMC10508026
Exploratory analyses
Exploratory analyses were conducted to investigate the source of the unexpected increased kcals ordered from the fast food outlet in proportional pricing conditions (Supplementary material XI). There was no main effect of pricing condition on kcals ordered from meals ordered, but there was for kcals from additional opt...
PMC10508026
Questionnaire responses
The majority (> 75%) of participants agreed that the virtual delivery app was representative of existing food delivery apps, and reported their orders where typical of what they would normally order. 20% of participants agreed that the food choices they made were influenced by how many calories they thought were in the...
PMC10508026
Discussion
SAID, SHOP
This study examined the impact of calorie labelling and proportional pricing in a virtual online food delivery platform on portion size choice, kcals ordered and hypothetical spend from beverage, sandwich and fast food outlets. Compared to non-labelling conditions, calorie labelling had no significant impact on portion...
PMC10508026
Strengths and limitations
eating disorders
SHOP
This study was pre-registered and was stratified to represent the UK population in terms of gender and education. While virtual methodologies for food ordering are widely used [As is standard practice in eating behaviour research, individuals who were currently dieting, fasting, or had a history of eating disorders we ...
PMC10508026
Conclusions
Calorie labelling on food delivery platforms may effectively reduce calories ordered. Proportional pricing may prompt consumers to select smaller portion sizes, although further research in real-world settings will now be valuable.
PMC10508026
Authors’ contributions
AF conceptualised the study, developed methodology, collected the data, validated the data, analysed the data, wrote the initial draft and had responsibility for the final manuscript. ER conceptualised the study, developed the methodology, and critically reviewed and revised the manuscript. AJ advised and helped to dev...
PMC10508026
Funding
Obesity
OBESITY
The first author (AF) is funded by an ESRC case studentship, grant no: ES/P000665/1, with a contribution from the Obesity Health Alliance. ER is funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant reference: PIDS, 803194) and the National Instit...
PMC10508026
Data Availability
The data that supports these findings will be available from the Open Science Framework repository upon publication (osf.io/kaju5 [
PMC10508026
Declarations
PMC10508026
Ethics approval and consent to participate
Ethical approval was obtained from the University of Liverpool ethics committee (approval code: 4612), and informed consent was obtained from all participants before they took part in the study.
PMC10508026
Consent for publication
Consent for publication has been obtained.
PMC10508026
Competing interests
ER has previously received research funding from Unilever and the American Beverage Association for unrelated research projects. Other authors have no competing interests.
PMC10508026
Abbreviations
KilocaloriesSocioeconomic positionBody Mass IndexSubjective Social Status
PMC10508026
References
PMC10508026
Background
Lateral Elbow Tendinopathy
The OPTimisE intervention was developed to address uncertainty regarding the most effective physiotherapy treatment strategy for people with Lateral Elbow Tendinopathy (LET).
PMC10843168
Objectives
To assess the feasibility of conducting a fully-powered randomised controlled trial (RCT) evaluating whether the OPTimisE intervention is superior to usual physiotherapy treatment for adults with LET.
PMC10843168
Design
A mixed-methods multi-centred, parallel pilot and feasibility RCT, conducted in three outpatient physiotherapy departments in the UK.
PMC10843168
Method
Patients were independently randomised 1:1 in mixed blocks, stratified by site, to the OPTimisE intervention or usual care. Outcomes were assessed using pre-defined feasibility progression criteria.
PMC10843168
Results
ADVERSE EVENTS
50 patients were randomised (22 Female, 28 Male), mean age 48 years (range 27–75). Consent rate was 71% (50/70), fidelity to intervention 89% (16/18), attendance rate in the OPTimisE group 82% (55/67) vs 85% (56/66) in usual care, outcome measure completion 81% (39/48) at six-month follow-up. There were no related adve...
PMC10843168
Conclusions
It is methodologically feasible to conduct a fully powered RCT comparing the clinical and cost-effectiveness of the OPTimisE intervention versus usual physiotherapy treatment. Considering the similar improvements observed in both groups, careful consideration is needed regarding the priority research question to be add...
PMC10843168
Introduction
elbow pain, Lateral elbow tendinopathy
TENNIS ELBOW
Lateral elbow tendinopathy (LET), also known as Tennis Elbow, is a common cause of elbow pain affecting sleep and basic daily activities, as well as sports, work and hobbies (The OPTimisE intervention was designed in consultation with patients and clinicians to reflect the current evidence base in a way that could be i...
PMC10843168
Method
PMC10843168
Trial design
We conducted a parallel two-arm, multi-centre pilot and feasibility randomised controlled trial across three sites. The detailed protocol has previously been published (
PMC10843168
Feasibility outcomes
RECRUITMENT, SECONDARY
Our primary aim was to determine feasibility (criteria shown in Consent rate (number consented from those eligible after screening for inclusion/exclusion criteria)Intervention fidelity in the intervention group (measured as a binary outcome if participants were given the orthosis, taught the progressive exercise regim...
PMC10843168
Participants
elbow pain, Maudsley, pain, PIS
TENNIS ELBOW
We piloted two methods of participant identification: screening of General Practice (GP) computer records and screening of referrals at physiotherapy sites. Those patients identified from GP records were sent a self-screening checklist and invitation letter to contact the trial team if they wished to be considered. The...
PMC10843168
Randomisation
Following assessment, we invited eligible patients to provide informed consent, complete baseline questionnaires and they were then randomised via an online service (Sealed Envelope™) using 1:1 allocation in mixed blocks or 2 and 4, stratified by treatment site. We also asked if they consented to be contacted about par...
PMC10843168
Interventions
orthosis, Epi-Hit®, pain
We allocated participants to receive either the OPTimisE intervention or usual physiotherapy care. We did not standardise usual care in this pragmatic trial but we recorded treatments received by participants, to allow comparison with the OPTimisE intervention. Physiotherapists providing usual care treatment had no res...
PMC10843168
Blinding
Due to the nature of the interventions, neither participants nor physiotherapists could be blinded. Data analysis was not masked to allocation.
PMC10843168
Data collection
TENNIS ELBOW
We gathered patient-reported data using a questionnaire containing the recommended Core Outcome Set for LET (Patient-Rated Tennis Elbow Evaluation (PRTEE),Participants were given the choice of receiving questionnaires by post or online, using the Amplitude Pro-One™ system (
PMC10843168
Analytical methods
PMC10843168
Quantitative data analysis
Descriptive statistics were used to summarise the distribution of baseline variables across each of the randomisation groups. The continuous baseline variables (e.g. age) were reported with means and 95% confidence intervals (95% CI), if shown to be normally distributed, otherwise were reported with medians and Interqu...
PMC10843168
Qualitative interviews
PIS
RECRUITMENT
At least three months after randomisation, we sent a purposive sample of patients a PIS and invitation letter to take part in a qualitative interview. We followed this up by telephone or email to gain provisional consent and organise a mutually convenient time. Similarly, physiotherapists involved in the trial were app...
PMC10843168
Data management
Data were collected using a mix of paper and electronic methods. Where possible a patient ID number was used rather than identifiable information. Data from paper forms were transcribed into an electronic database in Microsoft Excel stored on secure NHS servers. Paper hard copies were stored at Derby CTSU and in the re...
PMC10843168
Results
We recruited the target of 50 patients (stipulated by the funder) within the allocated 12-month time-period. Baseline data are displayed in Summary of baseline data.The CONSORT diagram is shown in CONSORT diagram.
PMC10843168
Feasibility outcomes
RECRUITMENT
We enrolled the target of 50 participants six weeks ahead of schedule (as shown in Recruitment graph.
PMC10843168
Secondary outcomes
orthosis, injuries
ADVERSE EVENTS, RECRUITMENT
Of the two patient recruitment methods, physiotherapy referral screening provided 49 participants, whereas only 1 participant was recruited from GP record screening (having identified 15 potentially eligible people).The outcome measure return rate at six weeks was 59% (66% online vs 36% paper); at 12 weeks was 65% (68%...
PMC10843168
Discussion
disability, NRS, pain
Our results suggest that it is feasible to conduct a full-scale trial to compare the clinical and cost-effectiveness of the OPTimisE intervention compared with usual NHS physiotherapy care. We successfully recruited to target ahead of schedule, but the number of eligible patients identified was lower than predicted bas...
PMC10843168
Conclusion
It is methodologically feasible to conduct a fully powered RCT to compare the clinical and cost-effectiveness of the OPTimisE treatment protocol against usual physiotherapy treatment. However, both intervention and usual care groups showed similar improvements over time, questioning the importance of a future comparati...
PMC10843168
Ethics approval and consent to participate
Approvals were received from the Yorkshire & The Humber - Sheffield Research Ethics Committee (reference 21-YH-0121) and the UK Health Research Authority (reference 297637) on June 22nd
PMC10843168
Trial registration
Registered with the ISRCTN database 19/7/2021.
PMC10843168
Funding
BATEMAN
Marcus Bateman is funded by a
PMC10843168
Patient and public involvement
orthosis
Patient volunteers were involved with the design of the OPTimisE intervention, selection of orthosis from a range of available products, generation of trial website frequently asked questions and review of trial resources. KC is a member of both the OPTimisE Patient and Public Involvement Group and Trial Management Gro...
PMC10843168
Authors’ contributions
MB, CL, NF, BS, BV and DD were involved in the preliminary design and funding application. MB, CL, NF, BS, JCH, BV, JB, KC, AS and DD designed the trial protocol. All authors contributed to the conduct and management of the trial. MB, BS, CL, KC and JCH conducted the qualitative data analysis. MB and JB conducted the q...
PMC10843168
Declaration of competing interest
The authors have no conflicts of interest to declare.This paper presents independent research funded by the
PMC10843168
References
PMC10843168
Supplementary data
The following are the Supplementary data to this article.
PMC10843168
Multimedia component 1
PMC10843168
1. Introduction
scaly, injury or cutaneous inflammation, SD
PATHOPHYSIOLOGY, INFLAMMATORY SKIN DISEASE, FACIAL SEBORRHEIC DERMATITIS, SEBORRHEIC DERMATITIS
Facial seborrheic dermatitis (SD) is an inflammatory skin disease characterized by erythematous and scaly lesions on the skin with high sebaceous gland activity. The yeast Seborrheic dermatitis (SD) is a chronic inflammatory skin disease characterized by erythematous, scaling, and indurated papules and plaques on the f...
PMC10531869
2. Results
A total of 115 patients were screened, of which 37 were enrolled into the study and 36 successfully completed the study (
PMC10531869
2.1. Omiganan Does Not Show Clinical Improvement Compared to Placebo
DISEASE
Disease severity did not significantly decrease in the omiganan group compared to the placebo, as scored by SDASI (−1.5, CI −3.6 to 0.5,
PMC10531869
2.2. Neither Omiganan Nor Ketoconazole Show Effects on Clinical Imaging Compared to Placebo
Erythema
ERYTHEMA
Erythema was comparable to the placebo in the omiganan group (−0.1682, 95% CI −2.9839 to 2.6475,
PMC10531869
2.3. Skin Barrier Function Improves upon Treatment with Ketoconazole
TEWL was not significantly reduced compared to the placebo at EOT for omiganan (−5.935, 95% CI −12.265 to 0.395,
PMC10531869
2.4. Ketoconazole but Not Omiganan Reduces Malassezia Abundances
Treatment with omiganan did not result in significant mycobial changes, with a −3.662% decrease in
PMC10531869
3. Discussion
SD, reduction of cutaneous inflammation
DISEASE, ATOPIC DERMATITIS, PATHOPHYSIOLOGY
The use of topical AMPs holds promise for the treatment of SD since both antifungal and antibacterial involvement has been previously established in this disease. In this randomized, comparator- and placebo-controlled clinical trial, the efficacy of 1.75% omiganan gel was compared to its vehicle and standard-of-care 2%...
PMC10531869
4. Materials and Methods
PMC10531869
4.1. Materials
ALDRICH
Chloroform (Honeywell, Charlotte, NC, USA), methanol (Biosolve, Valkenswaard, The Netherlands), heptane (LiChorSolv, Merck, Darmstadt, Germany), UPLC-grade isopropyl alcohol (Biosolve, Valkenswaard, The Netherlands), and ethanol (Biosolve, Valkenswaard, The Netherlands) were of HPLC grade or higher. Reagent-grade potas...
PMC10531869
4.2. Study Design, Randomization, and Treatments
The trial was registered under ClinicalTrials.gov Identifier NCT03688971 and EudraCT number 2017-003106-41. The study was performed from November 2019 to January 2022 at the Centre for Human Drug Research (Leiden, The Netherlands) following the Declaration of Helsinki principles and after obtaining ethical approval fro...
PMC10531869
4.3. Patients
IGA, SD
Included patients exhibited mild-to-moderate facial SD, as defined by an Investigator’s Global Assessment (IGA) score of ≤2 at screening, without any other clinically significant conditions, recent tanning, or recent exposure to other SD treatments. Recent exposure was defined as two weeks for topical treatments and an...
PMC10531869
4.4. Physician- and Patient-Reported Scoring
SEBORRHEIC DERMATITIS
SD severity was scored by the Seborrheic Dermatitis and Severity Index (SDASI) [
PMC10531869
4.5. Cutaneous Imaging
erythema
ERYTHEMA
Cross-polarized facial photography was performed using a VISIA-CR (Canfield Scientific, Parsippany-Troy Hills, NJ, USA). The erythema index was determined through ImageJ (version 1.51 h CITE) based on Yamamoto et al. [
PMC10531869
4.6. Trans-Epidermal Water Loss Measurements
Trans-epidermal water loss (TEWL) was determined using an AquaFlux AF200 (Biox Systems Ltd., London, UK) after the subjects acclimatized to the controlled environmental conditions (humidity < 60%, temperature 22 ± 2 °C) for at least 15 min. TEWL was normalized with an additional measurement of non-lesion skin elsewhere...
PMC10531869
4.7. Lipidomics Analysis Using Sebum Measurements and Liquid Chromatography-Mass Spectrometry after Tape-Stripping
Sebum levels were measured in triplicate on adjacent skin using a Sebumeter SM815 (Courage and Khazaka, Cologne, Germany). The average of three measurements was calculated. For lipidomics, the stratum corneum was sampled with 5 subsequent polyphenylene sulfide tape strips (Nichiban, Tokyo, Japan), of which the first on...
PMC10531869
4.8. Microbial Profiling
SKIN, STERILE, LYSIS
Skin was swabbed for 10 s while constantly rotating using a sterile polyester-tipped applicator (Puritan, Guilford, ME, USA) soaked in 0.9% NaCl. Swabs were stored in DNA/RNA shield lysis buffer and beat beads (Zymo Research, Irvine, CA, USA) at −80 °C until analysis. Extraction, sequencing, and data generation were pe...
PMC10531869
4.9. Malassezia Species Identification by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Agar plates of 5.5 cm in diameter with modified Dixon agar medium (Tritium Microbiology B.V., Eindhoven, The Netherlands) were pressed against the skin for 20 min. Plates were transferred to the Alrijne Hospital (Leiden, The Netherlands) and cultured for up to 21 days at 33 °C. If mycological growth was observed, an is...
PMC10531869
4.10. Statistical Analysis
Calculations were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA). Group size was based on a previous trial with omiganan with significant clinical effects rather than a formal power calculation [
PMC10531869
Supplementary Materials
The following supporting information can be downloaded at: Click here for additional data file.
PMC10531869
Author Contributions
Conceptualization, M.B.A.v.D., R.R., J.B., T.N.-v.d.K., G.L.F., M.S. and J.R.; methodology, M.B.A.v.D., R.R., T.N.-v.d.K., G.L.F., M.L.d.K. and J.R.; software, H.E.C.v.d.W.; formal analysis, M.L.d.K., H.E.C.v.d.W. and J.R.; investigation, M.B.A.v.D., T.N.-v.d.K., J.H., B.T., T.G., L.P., A.N., M.S. and J.R.; data curati...
PMC10531869
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and reviewed and approved by the Stichting Beoordeling Ethiek Biomedisch Onderzoek (IRB approval number: CHDR1733, NL62759.056.18, approved on 5 September 2018).
PMC10531869
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
PMC10531869
Data Availability Statement
The data that support the findings of this study are available from the corresponding author and/or trial sponsor upon reasonable request.
PMC10531869
Conflicts of Interest
Cutanea
MINOR
G.L.F. was an employee of Cutanea Life Sciences and involved in the design of the study and review and approval of the final manuscript. Comments made by G.L.F. were minor and did not change the message of the manuscript. The other authors have no conflict of interest to declare.
PMC10531869
References
ADVERSE EVENTS
(((The change in relative abundance of (Demographics of the study population and adverse events.
PMC10531869
Background
Blinding drugs through simulation techniques is an important means to control the subjective bias of investigators and subjects. However, clinical trials face significant challenges in the placebo production of drugs, and many trials cannot be double-blinded.
PMC10636892
Objective
BLIND
This study was conducted to ascertain the consistency between non-blind and blind evaluation results in clinical trials and to pioneer strategies to control information bias, particularly in trials where double-blinding is not feasible.
PMC10636892
Methods
Diabetic Foot (IWGDF), was used as the primary, DFIs
DIABETIC FOOT INFECTIONS, INFECTIOUS DISEASE
In this investigation, a randomized controlled trial (RCT) studying diabetic foot infections (DFIs) was utilized as a representative case. In this trial, the grading of DFIs, as per guidelines by the Infectious Disease Society of America (IDSA) and International Working Group on Diabetic Foot (IWGDF), was used as the p...
PMC10636892
Results
Five subjects were excluded due to the quality of photos or the lack of post-treatment visits. The post-treatment IDSA/IWGDF grading results were compared in 11 subjects (experimental group=6, control group=5), and the consistency test showed inconsistent results between the non-blinded and center reading blinded evalu...
PMC10636892
Conclusions
The study highlighted that evaluations from non-blinded site investigators may potentially exaggerate the efficacy of the experimental group and that deep wounds can present challenges for observation via center-reading photos. These findings underline the vital necessity for objective assessment in open clinical trial...
PMC10636892
Trial registration
ChiCTR2000041443. Registered on December 2020
PMC10636892
Supplementary Information
The online version contains supplementary material available at 10.1186/s13063-023-07652-y.
PMC10636892
Keywords
PMC10636892
Introduction
EVENT, BLIND
The application of the most reliable evidence to address individual clinical issues underpins the core principle of evidence-based medicine [However, due to the particularity of certain interventions, it becomes challenging to blind participants and investigators in some clinical trials. Recent investigations have high...
PMC10636892
Methods
PMC10636892
Designs
trauma, DFIs
DIABETIC FOOT INFECTIONS
A multicenter RCT on diabetic foot infections (DFIs) was taken as an example. This trial evaluated the efficacy and safety of a Chinese patent medicine. Patients with DFI, aged between 18 and 75 years, and IDSA/IWGDF grade 2 were included [There is a greater risk of using a placebo control for patients in this trial. F...
PMC10636892
Setting
This was an exploratory study, and we randomly selected only about 10% of the completed clinical trial subjects for blinded and unblinded evaluations (
PMC10636892
Non-blinded investigators
infection, fever, pain
INFECTION, APPENDIX
The IDSA/IWGDF grading of DFI was determined and recorded by a non-blinded investigator at the study center for post-treatment patients. A note was made as to whether the subject had local pressure or pain, local fever, systemic symptoms, or symptoms of infection at the time of photography. For the randomly selected su...
PMC10636892
Blinded investigators
center-reading
BLIND
Based on the “Study Center Grading Results Evaluation Form,” the center-reading investigators made independent determinations back-to-back in a blind state. A third center-reading investigator made a second determination if two center-reading investigators made inconsistent determinations.
PMC10636892
Evaluation
IDSA/IWGDF grading: Assessing the IDSA/IWGDF grading of non-blinded and blinded investigators.
PMC10636892
Quality control and assurance
Previously, we provided better training to the investigators involved in this study’s blinded and unblinded clinical assessment. We believe that the main source of the difference between blinded and unblinded researchers’ evaluation of post-treatment outcomes is evaluation bias, which is the effect of unblinded personn...
PMC10636892
Statistical analysis
An independent statistician will carry out statistical analysis using the SPSS 25 software. All statistical tests will be two-sided,
PMC10636892
Results
PMC10636892
Results for blinded evaluation
Among the 16 randomly enrolled patients, one was excluded due to a lack of post-treatment follow-ups, and 4 were unable to be analyzed as the central reader could not discern the deeper parts of the wounds from the photographs. The randomization and follow-up process for patients is illustrated in Fig. Flow chart for s...
PMC10636892
Considerations for blinded evaluation
In open clinical trials where wound observation serves as the primary efficacy measure, we recommend the appointment of an independent blinded investigator at each trial site, accompanied by the implementation of a series of standard operating procedures (SOPs) for blinded evaluation. The ensuing considerations for bli...
PMC10636892
Personnel roles and training
BLIND
We advise establishing clearly delineated roles among the research team, which may include treatment investigators, blinded evaluation investigators, research nurses, quality control officers, medication administrators, and documentation managers.The investigator responsible for efficacy evaluation remains blinded thro...
PMC10636892
Management of participants
Given the external nature of the treatment employed in this study, achieving absolute blinding of participants was challenging. First, both treatment investigators and research nurses should be strictly instructed not to reveal specific treatment protocol details to patients. Secondly, to minimize the potential for int...
PMC10636892
Management of experimental medications
EVENT
It is recommended that a medication manager be appointed within the study team, responsible for the receipt, storage, maintenance, distribution, and retrieval of medications. The medications should be stored in opaque medicine cabinets. Prior to prescribing, the treatment investigator must obtain a randomization number...
PMC10636892
Collection of efficacy indicators
infection, purulent
INFECTION, EPITHELIALIZATION
Though the wounds in this study were documented using digital photography and analyzed with image analysis software, factors such as environment, operational procedure, and patient positioning may influence the quality of the images. As such, a blinded assessment investigator should be assigned to document wound healin...
PMC10636892