Background and Aims Patients with severe alcohol‐associated hepatitis (AH) have high mortality. Corticosteroids improve survival only for 30 days. We targeted inflammation, cellular injury, and gut leakiness in a randomized clinical trial comparing combination therapy to corticosteroids on 180‐day survival. Approach and Results Subjects with a clinical diagnosis of severe AH (Model for End‐Stage Liver Disease [MELD] >20, Maddrey discriminant function [MDF] >32) were randomized to receive methylprednisolone (PRED; 28 days) or a combination of anakinra (14 days) plus pentoxifylline (28 days) plus zinc (COMB; 180 days). The primary endpoint was survival at 180 days. The study was designed in 2013, initiated in October 2014, and completed in March 2018. Five hundred patients were screened to randomize 104 subjects with a clinical diagnosis of AH with a MELD score >20. Fifty‐three patients were randomized into the COMB and 50 to the PRED treatment; 1 dropped out of the study before randomization. Mean age was 45.3 ± 10.4 years; 60.6% were males, 92.3% White, and mean MELD 25.7 ± 3.9. Kaplan‐Meier survival estimate at 180 days was 67.9% in COMB and 56% in PRED (HR = 0.69; p = 0.3001). Survival curves separated by 90 days (COMB, 69.8%; PRED, 58.0%; HR = 0.69; p = 0.28). Survival at 28 days was similar between the COMB (83.4%) and PRED groups (81.2%; HR = 0.91; p = 0.85). There were no unexpected serious adverse events, and incidence of infection was comparable between groups. MELD 20–25 and MELD >26 strata showed nonsignificant treatment effects in favor of COMB. Conclusions A combination of anakinra, pentoxifylline plus zinc provides similar survival benefits compared to corticosteroid therapy in severe AH.

Clinical investigators invoke a number of specific regulatory requirements if their study includes use of a pharmaceutical agent. Studies using a drug that has not been approved by the Food and Drug Administration (FDA) or for indications not in the approved labeling may require filing an Investigational New Drug (IND) application with the FDA. If a study meets specific regulatory exemption criteria, then an IND may not be needed. Individual investigators may meet the FDA definition of a sponsor-investigator, in which case the application process is generally less complicated than for commercial sponsors, and this review addresses only this circumstance. Filing an IND requires completion of 3 sets of forms: 1 detailing the study (FDA Form 1571), 1 providing information about the investigator and study site (FDA Form 1572), and 1 certifying that the study is registered in the national database of clinical trials (FDA Form 3674). If the IND is approved, the study may begin 30 days after the FDA acknowledges receipt and assigns an IND. If the FDA requires additional information or if the study is placed on a “clinical hold,” the study must not proceed. While the IND is active, the investigator must also continue to meet a set of regulations for monitoring the study and reporting to the FDA.

Introduction Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined.

PURPOSE The Food and Drug Administration Expanded Access (EA) program and “Right-to-Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. METHODS FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. RESULTS The FDA EA program includes Single Patient IND (SP-IND), Emergency SP-IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. “Right-to-Try” legislation bypasses some of these steps, but provides no regulatory or safety oversight. CONCLUSION The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP-IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements.

Background: During the COVID-19 public health emergency, the FDA and NIH altered clinical trial requirements to protect participants and manage study conduct. Given their detailed knowledge of research protocols and regular contact with patients, clinicians, and sponsors, clinical research professionals offer important perspectives on these changes. Methods: We developed and distributed an anonymous survey assessing COVID-19–related clinical trial adjustment experiences, perceptions, and recommendations to Clinical Research Office personnel at the Harold C. Simmons Comprehensive Cancer Center. Responses were compared using the Fisher exact test. Results: A total of 94 of 109 contacted research personnel (87%) responded. Among these individuals, 58% had >5 years’ professional experience in clinical research, and 56% had personal experience with a COVID-19–related change. Respondents perceived that these changes had a positive impact on patient safety; treatment efficacy; patient and staff experience; and communication with patients, investigators, and sponsors. More than 90% felt that positive changes should be continued after COVID-19. For remote consent, telehealth, therapy shipment, off-site diagnostics, and remote monitoring, individuals with personal experience with the specific change and individuals with >5 years’ professional experience were numerically more likely to recommend continuing the adjustment, and these differences were significant for telehealth (P=.04) and therapy shipment (P=.02). Conclusions: Clinical research professionals perceive that COVID-19–related clinical trial adjustments positively impact multiple aspects of study conduct. Those with greatest experience—both specific to COVID-19–related changes and more generally—are more likely to recommend that these adjustments continue in the future.