Rapid Web-Based Recruitment of Patients With Psoriasis: Multinational Cohort Study.

BACKGROUND: Wide-ranging patient recruitment not restricted to the location of the investigator will provide a better representation of the patient population in clinical studies. OBJECTIVE: Our goal was to assess the feasibility of a broad web-based recruitment strategy in an 8-week observational study of 500 study participants with psoriasis and healthy controls from locations remote from the investigator and to assess the cost associated with each participant. METHODS: A decentralized team in Denmark recruited patients with psoriasis and healthy controls using Google and Facebook advertisements and posts to Facebook groups. All individuals were screened via the internet, and patients diagnosed with psoriasis were included. Questionnaires regarding itch and sleep were completed by both groups at inclusion, week 4, and week 8. RESULTS: During a 2-week recruitment period, 12,887 unique advertisement views were registered, and 839 participants were enrolled, of which 507 completed the study (220 with psoriasis and 287 healthy controls) with a retention rate of 60.4%. Participants were recruited from 11 different countries on 4 separate continents, mainly from the United States, Canada, and the United Kingdom. The recruitment rate was 59.9 participants per day, and the conversion rate was 57.2%. Recruitment costs were US $13 per enrolled participant and US $22 per participant completing the study. CONCLUSIONS: It is feasible and rapid to recruit a large number of participants from locations different from the investigator and to retain patients in an observational study with no visits to a clinical site at low costs.

Investigating the efficacy and safety of calcipotriol/betamethasone dipropionate foam and laser microporation for psoriatic nail disease-A hybrid trial using a smartphone application, optical coherence tomography, and patient-reported outcome measures.

There is a lack of efficacious topical treatments for patients suffering from psoriatic nail disease (PND). We investigated the efficacy of Calcipotriol-Betamethasone Dipropionate (Cal/BD) foam with and without ablative fractional laser (AFL) in patients with PND. A total of 144 nails from 11 patients were treated in a 24-week long, open-label, randomized, intra-patient controlled proof-of-concept hybrid trial. In addition to daily Cal/BD foam application, half of each patient's psoriatic nails were randomized to receive optical coherence tomography (OCT)-guided AFL treatment at baseline, 6-, and 12-week follow-ups. In-clinic assessment (N-NAIL), patient-reported outcomes (PROMs), and drug consumption were supplemented by remote evaluation of 15 subclinical OCT features, smartphone app-based safety monitoring, and photo-based assessment (NAPSI). After 24 weeks of Cal/BD foam treatment, patients achieved a significant improvement (p < 0.001) in both clinical (N-NAIL -76%, NAPSI -68%) and subclinical (OCT -43%) PND severity as well as a 71% reduction in PROMs. AFL-assisted Cal/BD treatment led to higher clinical (N-NAIL -85%, NAPSI -78%) and OCT-assessed (-46%) reduction of PND signs than Cal/BD alone (N-NAIL -66%, NAPSI -58%, OCT -37%), but did not reach statistical significance. Smartphone app images documented adverse events and mild local skin reactions, particularly erythema (75%), laser-induced swelling (28%), and crusting (27%). This hybrid trial demonstrated a reduction in clinical NAPSI and N-NAIL scores, subclinical OCT features, and PROMs, suggesting that Cal/BD foam is a safe and efficacious treatment for PND. Larger trials are warranted to prove the clinical benefit of AFL pretreatment as a Cal/BD delivery enhancer.

Changes in key recruitment performance metrics from 2008-2019 in industry-sponsored phase III clinical trials registered at ClinicalTrials.gov.

BACKGROUND: Increasing costs and complexity in clinical trials requires recruitment of more narrowly defined patient populations. However, recruitment for clinical trials remains a considerable challenge. AIM: Our overall aim was to quantify recruitment performance in industry-sponsored phase III clinical trials conducted globally during 2008-2019 with primary aim to examine development of overall clinical trial measures (number of trials completed, number of participants enrolled, trial duration in months) and key recruitment metrics (recruitment rate, number of sites, number of patients enrolled per site). METHODS: The publicly available AACT database containing data on all trials registered at ClinicalTrials.gov since 2008 was used. The analysis was completed during three time periods from 2008-2019 of 4 years each. RESULTS AND CONCLUSION: Recruitment duration for industry-sponsored phase III clinical trials have increased significantly during the last 12 years from an average recruitment period of 13 months (IQR 7-23) in 2008-2011 to 18 months (IQR 11-28) in 2016-2019 (p = 0.0068). Further, phase III clinical trials have increased the number of registered sites per clinical trial by more than 30% during the last 12 years from a median number 43 sites (IQR 17-84) in 2012-2015 to 64 sites (IQR 30-118) in 2016-2019 (p = 0.025), and concurrently, the number of participants enrolled in clinical research has decreased significantly from 2012-2015 and 2016-2019 (p = 0.046). We believe that these findings indicate that recruitment for phase III clinical trials is less effective today compared to 12 years ago.

Mild to moderate atopic dermatitis severity can be reliably assessed using smartphone-photographs taken by the patient at home: A validation study.

BACKGROUND: The use of photographs to diagnose and monitor skin diseases is gaining ground. OBJECTIVES: To investigate the validity and reliability of photographic assessments of atopic dermatitis (AD) severity. METHODS: AD severity was evaluated in the clinic by two assessors using the Eczema Area and Severity Index (EASI), SCOring Atopic Dermatitis (SCORAD), and Investigator's Global Assessment (IGA). Participants photographed the lesions with their own smartphone and completed a questionnaire about the extent of eczema the same day from home. The photographs were assessed twice with an 8 weeks interval by five dermatologists experienced in photographic evaluations. Intraclass correlation coefficients (ICC) with 95% confidence interval (CI) were applied. RESULTS: Seventy-nine participants were enrolled. The ICC between clinical EASI and photographic EASI was 0.88 (95% CI 0.81-0.93), and 0.86 (0.70-0.93) between clinical SCORAD and photographic SCORAD. Perfect agreement between clinical IGA and photograph IGA was observed for 62%, with the difference between the two never deviating with more than 1 score. The inter-rater ICC for photographic EASI and photographic SCORAD, respectively, was 0.90 (0.85-0.94), and 0.96 (0.91-0.98). The intra-rater agreements between the first and second assessments varied from 0.95 to 0.98 for photographic EASI, and from 0.86 to 0.94 for photographic SCORAD. CONCLUSION: There was high agreement between mild to moderate AD severity assessed clinically and based on smartphone photographs. Further, the photographic assessments can be reproduced with high reliability.

Remote Rating of Atopic Dermatitis Severity Using Photo-Based Assessments: Proof-of-Concept and Reliability Evaluation.

BACKGROUND: Digital imaging of dermatological patients is a novel approach to remote assessment and has recently become more relevant since telehealth and remote decentralized clinical trials are gaining ground. OBJECTIVE: We aimed to investigate whether photographs taken by a smartphone are of adequate quality to allow severity assessments to be made and to explore the usefulness of an established atopic dermatitis severity assessment instrument on photograph evaluation. METHODS: During scheduled visits in a previously published study, the investigating doctor evaluated the severity of atopic dermatitis using the Scoring AD (SCORAD) index and took photographs of the most representative lesions (target lesions) with both a smartphone and a digital single-lens reflex camera (DSLR). The photographs were then assessed by 5 dermatologists using the intensity items of the SCORAD (iSCORAD), which consists of erythema, oedema/papulation, excoriations, lichenification, oozing/crusts, and dryness (scale 0-3, maximum score 18). The mean iSCORAD of the photographs was calculated and compared with in-person assessments using Pearson correlation and Bland-Altman plots. Intraclass correlation coefficients were used for interrater reliability. RESULTS: A total of 942 photographs from 95 patients were assessed. The iSCORAD based on smartphone photographs correlated strongly with the evaluations performed in person (iSCORAD: r=0.78, P<.001; objective SCORAD: r=0.81, P<.001; and total SCORAD: r=0.78, P<.001). For iSCORAD specifically, a Bland-Altman plot showed a difference in mean score of 1.31 for in-person and remote iSCORAD. In addition, the interrater agreement between the 5 rating dermatologists was 0.93 (95% CI 0.911-0.939). A total of 170 lesions were photographed, and the difference in mean scores was 1.32, 1.13, and 1.43 between in-person and remote evaluations based on photographs taken by a DSLR camera, a smartphone without flash, and a smartphone with flash, respectively. CONCLUSIONS: In terms of quality, remote atopic dermatitis severity assessments based on photographs are comparable to in-person assessments, and smartphone photos can be used to assess atopic dermatitis severity to a similar degree as photographs from a DSLR camera. Further, the variation in how the dermatologists in this study rated the iSCORAD based on the photographs was very low.

[Decentralised clinical trials].

Decentralised clinical trials are a modification of traditional clinical trials, which make studies cost-effective, time-saving and easier for participants. The use of digital solutions and health technologies in part or the entire trial process from patient recruitment, participant information, obtaining informed consent, clinical site visits, trial procedures, sampling, medication administration and safety monitoring enables for more effective conduct of the trial. Collecting data from multiple digital platforms allows for better and continuous monitoring of trial participants. In this review, we summarise those points.

Improved patient satisfaction and diagnostic accuracy in skin diseases with a Visual Clinical Decision Support System-A feasibility study with general practitioners.

Patient satisfaction is an important indicator of health care quality, and it remains an important goal for optimal treatment outcomes to reduce the level of misdiagnoses and inappropriate or absent therapeutic actions. Digital support tools for differential diagnosis to assist clinicians in reaching the correct diagnosis may be helpful, but how the use of these affect patients is not clear. The primary objective of this feasibility study was to investigate patient experience and satisfaction in a primary care setting where general practitioners (GPs) used a visual clinical decision support system (CDSS) compared with standard consultations. Secondary objectives were diagnostic accuracy and length of consultation. Thirty-one patients with a dermatologist-confirmed skin diagnosis were allocated to consult GPs that had been randomized to conduct either standard consultations (SDR, n = 21) or CDSS (n = 16) on two separate study days one week apart. All patients were diagnosed independently by multiple GPs (n = 3-8) in both the SDR and CDSS study arms. Using the CDSS, more patients felt involved in the decision making (P = 0.05). In addition, more patients were exposed to images during the consultations (P = 6.8e-27), and 83% of those that were shown images replied they felt better supported in the consultation. The use of CDSS significantly improved the diagnostic accuracy (34%, P = 0.007), and did not increase the duration of the consultation (median 10 minutes in both arms). This study shows for the first time that compared with standard GP consultations, CDSS assist the GP on skin related diagnoses and improve patient satisfaction and diagnostic accuracy without impacting the duration of the consultations. This is likely to increase correct treatment choices, patient adherence, and overall result in better healthcare outcomes.

High adherence and low dropout rate in a virtual clinical study of atopic dermatitis through weekly reward-based personalized genetic lifestyle reports.

INTRODUCTION: Clinical trials often suffer from significant recruitment barriers, poor adherence, and dropouts, which increase costs and negatively affect trial outcomes. The aim of this study was to examine whether making it virtual and reward-based would enable nationwide recruitment, identify patients with variable disease severity, achieve high adherence, and reduce dropouts. METHODS: In a siteless, virtual feasibility study, individuals with atopic dermatitis (AD) were recruited online. During the 8-week study, subjects used their smartphones weekly to photograph target AD lesions, and completed patient-oriented eczema measure (POEM) and treatment use questionnaires. In return, subjects were rewarded every week with personalized lifestyle reports based on their DNA. RESULTS: Over the course of the 11 day recruitment period, 164 (82% women and 18% men) filled in the form to participate, of which 65 fulfilled the inclusion criteria and signed the informed consent. Ten were excluded as they did not complete the mandatory study task of returning the DNA sample. 55 (91% women, 9% men) subjects returned the DNA sample and were enrolled throughout Denmark, the majority outside the Copenhagen capital region in rural areas with relatively low physician coverage. The mean age was 28.5 (SD ±9.5 years, range 18-52 years). The baseline POEM score was 14.5±5.6 (range 6-28). Based on the POEM, 7 individuals had mild, 28 had moderate, 17 had severe, and 3 had very severe eczema. The retention rate was 96% as 53 out of 55 enrolled completed the study. The adherence was very high, and more than 90% of all study tasks were completed. Follow up of 41 subjects showed that 90% would take part again or continue if the study had been longer. CONCLUSION: A virtual trial design enables recruitment with broad geographic reach and throughout the full spectrum of disease severity. Providing personalized genetic reports as a reward seems to contribute to high adherence and retention.

Virtual Clinical Trials: Perspectives in Dermatology.

BACKGROUND: The cost of developing a new drug is approximately USD 2.6 billion, and over two-thirds of the total cost is embedded in the clinical-testing phase. Patient recruitment is the single biggest cause of clinical trial delays, and these delays can result in up to USD 8 million per day in lost revenue for pharmaceutical companies. Further, clinical trials struggle to keep participants engaged in the study and as many as 40% drop out. To overcome these challenges pharmaceutical companies and research institutions (e.g., universities) increasingly use an emerging concept: virtual clinical trials (VCT) based on a remote approach. SUMMARY: VCT (site-less) are a relatively new method of conducting a clinical trial, taking full advantage of technology (apps, monitoring devices, etc.) and inclusion of web platforms (recruitment, informed consent, counselling, measurement of endpoints, and any adverse reactions) to allow the patient to be home-based at every stage of the clinical trial. Studies have shown that VCT are not only operationally feasible, but also successful. They have higher recruitment rates, better compliance, lower drop-out rates, and are conducted faster than traditional clinical trials. The visual nature of dermatological conditions, the relative ease in evaluating skin diseases virtually, and the fact that skin diseases often are not life-threatening and rarely require complex examinations make VCT very attractive for dermatological research. Further, making correct diagnoses based on photographs and patient symptomatology has always been part of the dermatologist's routine. Thus, VCT are in many ways made for dermatology. Herein we describe VCT and their implications in dermatological research.

Biological Effects of Ingenol Mebutate Gel in Moderate to Severe Actinic Fields Assessed by Reflectance Confocal Microscopy: A Phase I Study.

Ingenol mebutate represents a topical treatment for fields with actinic keratosis (AK). The biological effects of ingenol mebutate in AK, subclinical (SC)-AK, and reference-skin were assessed and graded by in vivo reflectance confocal microscopy (RCM) and histology. Patients with AK and SC-AK lesions in one 25 cm2 field on hands or forearms, and with an area of reference skin on the inner upper arm, were included. The two fields were each treated with ingenol mebutate 0.05% gel (n=16), or vehicle (n=8), on 2 consecutive days; clinical and RCM assessments were performed on days 1, 2, 3, 8, and 57, and biopsies on day 3. Local skin responses were more pronounced in AK fields (6.1 (mean) ± 2.6 (SD)) compared with reference skin (3.5 ± 1.5). The clinical AK lesion reduction was 43.8% and 6.3% with ingenol mebutate and vehicle, respectively. RCM and histology evaluations showed that ingenol mebutate induced a significant pronounced cell death and immune response in AK and SC-AK lesions, compared with reference skin. Ingenol mebutate induced RCM-measured reduction in (investigator-1/investigator-2): AK lesions (34/28%), SC-AK lesions (72/56%), and solar elastosis in AK fields (mean, -0.22/-0.25). In conclusion, ingenol mebutate showed selective pronounced biological responses in AK and SC-AK as compared with reference skin.

J Drugs Dermatol. 2016;15(10):1181-1189.

Repeated Treatments with Ingenol Mebutate Prevents Progression of UV-Induced Photodamage in Hairless Mice.

BACKGROUND AND AIM: Ingenol mebutate (IngMeb) is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local skin responses (LSR). METHODS: Hairless mice (n = 60; 3 groups of 20 mice) were irradiated with solar simulated ultraviolet radiation (UVR) throughout the study. Five single treatments with IngMeb were given at 4-week intervals (Days 21, 49, 77, 105, and 133). Clobetasol propionate (CP) was applied once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 (Days 28, 84, and 140), biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale (0-12). LSR (0-24) were assessed once daily (Days 1-7) after each IngMeb treatment. RESULTS: IngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 (UVR 10.25 vs. UVR+IngMeb 6.00, p = 0.002) compared to UVR alone. IngMeb induced LSR, including erythema, flaking, crusting, bleeding, vesiculation, and ulceration. Concurrent CP increased LSR (max LSR Tx 1-5: UVR+IngMeb+CP 3.6-5.5 vs. UVR+IngMeb 2.6-4.3) and provided better prevention of photodamage compared to IngMeb alone (Day 140: UVR+IngMeb 6.00 vs. UVR+IngMeb+CP 3.00 p < 0.001). CONCLUSION: Repeated field-directed treatments with IngMeb prevent progression of cutaneous photodamage in hairless mice, while CP cannot be used to alleviate IngMeb-induced LSR. The findings suggest that IngMeb may potentially serve as a prophylactic treatment for UV-induced tumors.