@article{f8fdb8bc5763442781afe3c55e06f271,
title = "Challenges in Patient Enrollment and Retention in Clinical Studies for Alcoholic Hepatitis: Experience of the TREAT Consortium",
abstract = "The TREAT Consortium has carried out clinical studies on alcoholic hepatitis (AH) for over 4 years. We encountered problems with participant recruitment, retention, and eligibility for specific protocols. To improve our ability to carry out such trials, we reviewed recruitment screening logs, end of study logs, and surveyed study coordinators to learn the reasons for missing patients, why patients declined enrollment, and the number of patients eligible for treatment trials. Associations of the recruited subjects{\textquoteright} demographics with their adherence to follow-up appointments were examined. Three hundred eight-seven patients (AH and heavy drinking controls) were enrolled in the observational study, and 55 AH patients were recruited into treatment trials. About half of patients identified with AH could not be recruited; no specific reason could be determined for about two-thirds of these. Among the patients who gave a reason for not participating, the most common reasons were feeling too sick to participate, desire to concentrate on abstinence, and lack of interest in research. Approximately a quarter of the AH patients met eligibility criteria for treatment trials for moderate or severe AH and we were able to recruit half to two-thirds of those eligible. Approximately 35% of participants in the observational study returned for both 6- and 12-month follow-up visits. We did not identify biopsychosocial or demographic correlates of retention in the study. This analysis revealed that attempts at recruitment into trials for AH miss some subjects because of structural issues surrounding their hospital admission, and encounter a high rate of patient refusal to participate. Nonetheless, more than half of the patients who met the eligibility criteria for moderate or severe AH were entered into clinical trials. Retention rates for the observational study are relatively low. These findings need to be accounted for in clinical trial design and power analysis.",
keywords = "Alcoholic Hepatitis, Clinical Trial, Model for End-Stage Liver Disease Score, Recruitment, Retention",
author = "Megan Comerford and Spencer Lourens and Suthat Liangpunsakul and Chalasani, {Naga P.} and Sanyal, {Arun J.} and Shah, {Vijay H.} and Kamath, {Patrick S.} and Puneet Puri and Katz, {Barry P.} and Svetlana Radaeva and Crabb, {David W.}",
note = "Funding Information: This study is supported by NIH/NIAAA 5U01AA021840, AA021883, AA21891, and AA021788 to the Translational Research and Evolving Alcoholic hepatitis Treatment (TREAT) Consortium. Alcoholic hepatitis (AH) is a serious public health problem with a high mortality rate. When severe, as judged by the model for end-stage liver disease (MELD) over 19 or Maddrey discriminant function over 32, mortality approaches 50% within the first 30 to 90 days; those surviving the acute phase still carry a high risk of dying in the ensuing year (Mathurin and Bataller,). Analysis of hospital and insurance administrative data suggests that the incidence of AH is rising (Jinjuvadia and Liangpunsakul,). The only widely used therapy, corticosteroids, is at best modestly effective and has significant contraindications and side effects. No new therapies are near introduction into clinical practice. Animal models for AH do not fully recapitulate the human disease; thus, clinical research is vital to this field for the development of new treatment modalities and noninvasive diagnostic techniques. In response to the dearth of treatment options for these patients, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has funded 4 consortia to accelerate AH research. The Translational Research and Evolving Alcoholic Hepatitis Treatment (TREAT) Consortium launched an observational study (TREAT001) in 2012 for patients with AH, defined as recent onset of jaundice (bilirubin >2 mg/dl), aspartate transaminase (AST) >50U/l, and a history of heavy alcohol consumption (>40 g per day on average in women and 60 g per day in men) for a minimum of 6 months and within the 6 weeks prior to study enrollment. The patients underwent clinical evaluation and appropriate laboratory testing to exclude confounding issues (negative markers for autoimmune liver disease and metabolic liver disease; absence of sepsis, shock, cocaine use, or recent drug use with drug-induced liver injury potential within 30 days). Coexisting HCV or HBV infection did not mandate a liver biopsy if other features were consistent with AH. With confounding factors, or atypical laboratory tests (AST <50 or >400IU/ml, AST/alanine aminotransferase (ALT) ratio <1.5, antinuclear antibody >1:160 or smooth muscle antibody >1:80), a liver biopsy (if clinically feasible and the subject has no contraindications) was required. TREAT001 also includes heavily drinking controls who are individuals with no history of alcoholic liver disease, AST and ALT ≤50 U/l, and normal total bilirubin. This study required completion of several survey instruments, a physical examination with anthropomorphic measurements, and collection of biosamples (blood, urine, stool) for archiving. Participants are scheduled to return for follow-up visits at 6 and 12 months. Study participants receive a payment of up to $255 dollars for completing all study visits and vouchers to cover parking expenses when applicable. TREAT also conducts phase 1 and 2 clinical trials for patients with moderate (MELD < 20) and severe AH (MELD >19 but <29). Clinical trial participants are randomized to placebo or active drug and require more frequent follow-up visits during the treatment phase. All treatment trial participants are concurrently enrolled in the observational study. Recruitment and retention of subjects in clinical trials related to alcohol abuse are difficult. These challenges have been discussed with regard to 2 very large randomized, controlled trials carried out with NIAAA support over the last several decades, Project MATCH (Zweben et al.,) and the COMBINE Study (Zweben et al.,). These studies examined various alcohol abuse treatments and required frequent contact as part of their patients{\textquoteright} therapy. To extend these analyses and explore possible additional issues related to recruitment and retention of patients with liver disease in addition to alcohol use disorders, we reviewed 4 years of experience in TREAT. We examined reasons patients gave for not participating in the studies, and factors correlating with failure to complete 6- and 12-month follow-up visits. To improve patient recruitment for future clinical trials, we analyzed the TREAT001 patients to see what proportion would be eligible for the current trials and our success in recruiting them. Strategies to improve enrollment and retention are suggested, based on the experiences of the study coordinators and investigators. Funding Information: This study is supported by NIH/NIAAA 5U01AA021840, AA021883, AA21891, and AA021788 to the Translational Research and Evolving Alcoholic hepatitis Treatment (TREAT) Consortium. Publisher Copyright: Copyright {\textcopyright} 2017 by the Research Society on Alcoholism",
year = "2017",
month = dec,
doi = "10.1111/acer.13515",
language = "English (US)",
volume = "41",
pages = "2000--2006",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "12",
}