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Supplemental Digital Content is available in the text.The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.

Background: Janssen Research & Development, LLC, part of the Janssen pharmaceutical companies of Johnson & Johnson, and NYU School of Medicine partnered to establish the Compassionate Use Advisory Committee (CompAC) to evaluate the use of an independent, external, expert committee in ensuring transparent, fair, beneficent, evidence-based, and patient-focused compassionate access to investigational medicines, a public health challenge that has been an ongoing issue for over 3 decades.Methods: To this end, NYU School of Medicine was responsible for the formation, member selection, and operation of CompAC, consisting of physicians, ethicists, and patient advocates, under Johnson & Johnson’s sponsorship.Results: A pilot was successfully run using CompAC to provide recommendations on compassionate use access to a Johnson & Johnson oncology investigational asset called daratumumab.Conclusion: This innovative model provides a framework that can be emulated by the industry globally.

Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 α-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 α-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 α-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.

We determined the effect of long-term treatment with finasteride on the incidence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH) related surgery in men with BPH.

We determine the effect of long-term suppression of dihydrotestosterone with finasteride, a specific type II 5α-reductase inhibitor, on bone mineral density.

Background:Finasteride, an inhibitor of type 2 5α-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. Objective:The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. Methods:In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. Results:After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. Conclusion:In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning. (J Am Acad Dermatol 2000;43:768-76.)

Objectives:Knowledge regarding the incidence and prevalence of acute urinary retention and the ultimate outcome is very limited. The purpose of the present analysis was to document the natural history and outcomes of acute urinary retention (AUR) further specified as being either precipitated or spontaneous, and to evaluate the potential benefit of finasteride therapy.Materials and Methods:Three thousand and forty men with moderate to severe symptoms of BPH and enlarged prostate glands by digital rectal examination were enrolled into the 4–year placebo–controlled PLESS trial and were evaluated for occurrences of AUR and BPH–related surgery. Men in the study were seen every 4 months; discontinued patients were followed up 6 months after discontinuation and again at the end of the 4–year trial. Complete 4–year data on outcomes (occurrence of AUR or BPH–related surgery) was available for 92% of the enrolled subjects in each treatment group. An endpoint committee, blinded to treatment group and center, reviewed and categorized all study–related documentation relating to retention and surgery.Results:Over the 4–year period, 99 of 1,503 placebo–treated patients (6.6%) experienced one or more episodes of AUR in comparison with 42 or 1,513 finasteride–treated patients (2.8%; p<0.001). Approximately half of the episodes of retention were spontaneous and clearly BPH–related, while the other episodes were precipitated by another factor (PAUR). After spontaneous AUR, subsequent surgery was performed in 39 of 52 (75%) placebo–treated patients versus 8 of 20 (40%) finasteride–treated patients (p = 0.01). BPH–related surgery was less common in men who had a prior episode of PAUR (26% in the placebo group and 14% in the finasteride group).Conclusion:There is a continual risk of spontaneous and precipitated acute urinary retention in men with moderate to severe lower urinary tract symptoms and an enlarged prostate gland. Fewer patients who developed precipitated AUR than spontaneous AUR go on to need subsequent BPH–related surgery. Significantly fewer finasteride–than placebo–treated patients developed AUR, and among those men, fewer ultimately needed BPH–related surgery.

We analyze patterns of prostate growth in men diagnosed with benign prostatic hyperplasia (BPH) and treated with placebo during 4 years, and determine which baseline parameters were the strongest predictors of growth.

Objectives. To determine whether baseline prostate-specific antigen (PSA), in addition to prostate volume, is associated with long-term changes in symptoms and urinary flow rate. Methods. Three thousand forty men with benign prostatic hyperplasia enrolled in the PLESS trial were randomly assigned to finasteride 5 mg or placebo for 4 years. Symptoms and flow rate were assessed every 4 months, and data were analyzed by dividing the patients into three groups by baseline PSA tertiles (0 to 1.3, 1.4 to 3.2, and 3.3 ng/mL or greater) and baseline prostate volume tertiles (14 to 41, 42 to 57, and 58 to 150 mL). Results. After the initial placebo effect, a slow deterioration in symptoms over time was observed in the placebo-treated men with a baseline PSA 1.4 ng/mL or greater. However, placebo-treated men in the lowest PSA tertile (less than 1.4 ng/mL) had sustained symptomatic improvement that was not seen in placebo-treated men in the higher tertiles ( P &lt;0.001). In all finasteride-treated groups, there was initial improvement followed by maintenance or continued symptom improvement over time (∼3 to 3.5 points by the end of 4 years). The differences in symptom score improvement between placebo and finasteride were marginal for men with baseline PSA levels less than 1.4 ng/mL ( P = 0.128) but were highly significant for men with PSA levels 1.4 ng/mL or greater ( P &lt;0.001). Urinary flow rate results were similar to those observed for symptoms. Analysis of symptom and flow rate data by prostate volume tertiles in a 10% subset of men yielded similar results, namely a deterioration of symptoms and flow rate in the two higher tertiles treated with placebo (greater than 41 mL) and a sustained improvement in all three groups of finasteride-treated patients. Conclusions. Baseline PSA and prostate volume are good predictors of long-term symptomatic and flow rate changes. Baseline PSA levels of 1.4 ng/mL or greater and enlarged prostate glands predict the best long-term response to finasteride compared with placebo.

Objectives. To investigate the long-term effects of finasteride on bother and health-related quality of life (HRQOL) in men with symptomatic benign prostatic hyperplasia. Methods. A large prospective 4-year placebo-controlled trial (PLESS) of 3040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate was performed that included self-administered questionnaires assessing HRQOL. Results. Significantly greater reductions in bother score were seen for finasteride compared with placebo at every time point after 4 months. Analysis of bother scores by baseline serum prostate-specific antigen (PSA), as it is highly correlated with prostate volume, suggested greater differences from placebo for men with PSA 1.4 ng/mL or greater, primarily due to worsening after the first-year improvement in the placebo group. An activity interference domain score was significantly improved for finasteride over placebo at each time point ( P &lt;0.01), with greater treatment differences in men with higher baseline PSA levels. Comparable results were seen for worry at each time point and embarrassment due to urinary symptoms in the last 2 years of the trial. Mean changes in sexual interest and satisfaction were somewhat better for the placebo group overall, as has been previously reported, but little difference between treatments was found in sexual satisfaction measures for men with PSA 1.4 ng/mL or greater. Conclusions. Compared with placebo, men receiving finasteride had significantly less bother, activity interference, and worry due to urinary symptoms, with more pronounced differences for men with baseline PSA 1.4 ng/mL or greater. As expected, sexual satisfaction and sexual drive were slightly worse for finasteride overall, but little difference in sexual satisfaction measures was found for men with a higher baseline PSA. Thus, HRQOL was improved for finasteride compared with placebo, especially for men with a baseline PSA 1.4 ng/mL or greater.

Hair regrowth was evaluated by histologic analysis in men and women treated for androgenetic alopecia, by counting follicles in horizontal sections of scalp biopsies. Serial 4 mm punch biopsies were taken at baseline and after 12mo of treatment from the transitional area of hair thinning between normal hair and vertex balding in men, and in an area of frontal/parietal thinning in women. Horizontal sections of recticular and papillary dermis were read by one observer, blinded to patient, treatment, and time. All terminal harir bulbs, terminal anagen and telogen hairs, and vellus and vellus-like miniaturized haris were counted. Twenty-six men aged 18–41y, comprising 14 on finasteride 1 mg daily and 12 on placebo, and 94 postmenopausal women, aged 41–60y, comprising 44 on finasteride 1 mg daily and 50 on placebo, were evaluated. In the male study, the terminal hairs increased from a mean baseline count of 15.5–20.9 after 12mo of finasteride, versus 17.3–18.3 in the placebo patients. The miniaturized hairs decreased from 26.7 to 23.6 with finasteride versus 21.3–20.3 with placebo. The terminal-to-vellus ratio increased more in the finasteride than in the placebo patients, suggesting some reversal of the miniaturization process with finasteride. In the female study, no significant differences in follicular counts in horizontal sections provide an informative adjunct to noninvative measures used in hair growth studies. Finasteride apears to be capable of reversing hair miniaturization in androgenetic alopecia in young to middle-aged men, but not in postmenopausal women.Journal of Investigative Dermatology Symposium Proceedings (2004) 4, 282–284; doi:10.1038/sj.jidsp.5640230