The Food and Drug Administration's Role in Dermatologic Drug Development.

The mission of the Food and Drug Administration (FDA) is to ensure the safety and effectiveness of dermatologic drugs, as authorized by the Federal Food, Drug, and Cosmetic Act (FD&CA). In this article, we discuss how the FDA's policies and practices have continued to evolve to incorporate scientific advances and to facilitate approval for dermatologic drugs in a timely manner for a broad spectrum of patients. We provide several examples to highlight areas where the Division of Dermatology and Dentistry found common ground with stakeholders to increase the therapeutic options for dermatologic patients, while still maintaining regulatory standards required for approval.

Measuring What Matters to Patients in Dermatology Drug Development: A Regulatory Perspective.

Incorporating the patient voice into drug development and regulatory review process allows for the science of drug development to be more patient-centered. Dermatology is one therapeutic area where patients have the potential to provide valuable perspectives on symptoms, functional impacts, and aesthetic outcomes. Patient-reported and observer-reported outcomes play an important role in capturing concerns related to the disease or condition and its treatment. Patient experience data from well-designed trials are critical for regulatory decision-making and ultimately enable prescribers and patients to make better informed treatment decisions at the point of care.

Food and Drug Administration perspective: Advancing product development for non-healing chronic wounds.

The US Food and Drug Administration (FDA) understands that innovative product development is essential to addressing the unmet medical need of non-healing chronic wounds. Barriers to product development for non-healing chronic wounds may involve but are not limited to a dearth of biological models, challenges in drug delivery, challenges in clinical trial execution, and limited commercial viability. This perspective article discusses FDA's renewed focus on non-healing chronic wounds and outlines efforts to address identified barriers to product development for non-healing chronic wounds. In collaboration with key wound healing stakeholders including academia, professional associations, patient groups, reimbursement organizations and industry, FDA intends to help advance product development for non-healing chronic wounds for the ultimate betterment of patients.

International Dermatology Outcome Measures (IDEOM): Report from the 2020 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) initiative is a non-profit organization that aims to develop evidence-based outcome measurements to evaluate the impact of treatments for patients with dermatological disease. IDEOM includes all key stakeholders in dermatology (patient, physician, industry, insurer, and government) during the process of developing such outcome measurements. SUMMARY: Here, we provide an update of IDEOM activities that were presented at the 2020 IDEOM Virtual Annual Meeting (October 23-24, 2020). During the meeting, multiple IDEOM workgroups (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) shared their progress to date, as well as future directions in developing and validating Patient-Reported Outcome Measures. Updates on demonstrating efficacy in clinicals trials by the US Food and Drug Administration are also summarized. KEY MESSAGES: In this report, we summarize the work presented by each IDEOM workgroup (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) at the 2020 IDEOM Virtual Annual Meeting.

Model-Informed Drug Development Approach Supporting Approval of Adalimumab (HUMIRA) in Adolescent Patients with Hidradenitis Suppurativa: a Regulatory Perspective.

On October 16, 2018, FDA expanded the adalimumab dosing regimen to adolescent hidradenitis suppurativa (HS) patients 12 years and older, weighing at least 30 kg without new clinical data. This approval was mainly supported by the model-informed drug development approach. Population pharmacokinetic simulations suggest body weight-tiered dosing regimens in adolescent patients will achieve similar exposure to adult patients across all weight range. Adalimumab has a well-established, 16-year long-term safety profile in various diseases in adult and pediatric populations. Current data of adalimumab in the pediatric population demonstrate no exposure-response relationship for adverse events. The effectiveness in adolescent patients was extrapolated from two adequate and well-controlled phase 3 studies in adult patients, assuming similar positive exposure-efficacy relationships in adults and adolescents. This article provides the insight of the application of MIDD on the adalimumab approval in adolescent HS patients and its implication on drug development and regulatory decision especially for pediatrics or rare diseases.

Does an increase in serum creatinine always reflect renal injury? The case of Stribild®

Single tablet, once-daily HIV treatment regimens offer patient convenience, the potential for increased adherence, and fewer patient-related dosing errors[1] . Stribild® (manufactured and marketed by Gilead Sciences; referred to as "applicant" in this report), a 4-drug fixed-dose combination (FDC) tablet, is approved for the treatment of HIV-1 infection in treatment-naïve adult patients. Stribild® contains elvitegravir (an integrase strand transfer inhibitor), cobicistat (an inhibitor of cytochrome P450 enzymes), and the nucleoside/nucleotide reverse transcriptase inhibitors emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF).

No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis.

BACKGROUND: Several studies have reported an association between abacavir (ABC) exposure and increased risk of myocardial infarction (MI) among HIV-infected individuals. Randomized controlled trials (RCTs) and a pooled analysis by GlaxoSmithKline, however, do not support this association. To better estimate the effect of ABC use on risk of MI, the US Food and Drug Administration (FDA) conducted a trial-level meta-analysis of RCTs in which ABC use was randomized as part of a combined antiretroviral regimen. METHODS: From a literature search conducted among 4 databases, 26 RCTs were selected that met the following criteria: conducted in adults, sample size more than 50 subjects, status completed, not a pharmacokinetic trial, and not conducted in Africa. The Mantel-Haenszel method, with risk difference and 95% confidence interval, was used for the primary analysis, along with additional alternative analyses, based on FDA-requested adverse event reports of MI provided by each investigator. RESULTS: The 26 RCTs were conducted from 1996 to 2010, and included 9868 subjects (5028 ABC and 4840 non-ABC). Mean follow-up was 1.43 person-years in the ABC group and 1.49 person-years in the non-ABC group. Forty-six (0.47%) MI events were reported [24 (0.48%) ABC and 22 (0.46%) non-ABC], with no significant difference noted between the 2 groups (risk difference of 0.008% with 95% confidence interval: -0.26% to 0.27%). CONCLUSIONS: To the best of our knowledge, our study represents the largest trial-level meta-analysis to date of clinical trials in which ABC use was randomized. Our analysis found no association between ABC use and MI risk.

Current advances in pharmacovigilance in the USA and Europe: meeting the challenges of safety monitoring in HIV.

PURPOSE OF REVIEW: The success of antiretroviral therapy in HIV disease comes currently with the realization that patients are committed to life-long treatment, which raises the possibility of long-term toxicity. Such long-term side effects may not be identified in initial clinical trials requiring, therefore, a different approach to monitoring patients over time - a pharmacovigilance approach. RECENT FINDINGS: Several key issues in long-term management of HIV infection have been addressed by a pharmacovigilance approach - including unusual and rare side effects and elucidation of emerging toxicities such as cardiovascular, bone and renal disease. Recent changes in legislation in the USA and Europe are aimed to strengthen pharmacovigilance in developed countries. SUMMARY: HIV infection and its treatment provide an important example of the role of pharmacovigilance. As clinical trials can rarely address the question of long-term tolerability, effective pharmacovigilance programs are and will remain essential.