Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021.

BACKGROUND & AIMS: Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. METHODS: We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH). RESULTS: Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020. CONCLUSIONS: Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Cost-effectiveness analysis of branded and authorized generic celecoxib for patients with chronic pain in Japan.

OBJECTIVES: The aim of this study was to examine the cost-effectiveness of branded and authorized generic (AG) celecoxib for chronic pain patients with osteoarthritis (OA), rheumatoid arthritis (RA), and low back pain (LBP), using real-world cost information for loxoprofen and pharmacotherapy for gastrointestinal bleeding. METHODS: This cost-effectiveness analysis was performed as a long-term simulation using the Markov model from the Japanese public healthcare payer's perspective. The analysis was conducted using loxoprofen with real-world weighted price by branded/generic distribution (hereinafter, loxoprofen with weighted price) as a comparator. In the model, we simulated the prognosis of patients with chronic pain by OA, RA, and LBP treated with loxoprofen or celecoxib, over a lifetime period. RESULTS: A cost-increase of 129,688 JPY (1,245.00 USD) for branded celecoxib and a cost-reduction of 6,268 JPY (60.17 USD) for AG celecoxib were recognized per patient in lifetime horizon, compared to loxoprofen with weighted price. No case was recognized to reverse the results of cost-saving by AG celecoxib in one-way sensitivity analysis. The incremental cost-effectiveness ratio of branded celecoxib attained 5,403,667 JPY/QALY (51,875.20 USD/QALY), compared to loxoprofen with the weighted price. CONCLUSION: The current cost-effectiveness analysis for AG celecoxib revealed its good value for costs, considering the patients' future risk of gastrointestinal injury; also, the impact on costs due to AG celecoxib against loxoprofen will be small. It implies that the disadvantage of AG celecoxib being slightly more expensive than generic loxoprofen could be offset by the good cost-effectiveness during the prognosis.

[Functional Exams in the gastroenterology - new developments and tips for the common practice]. / Gastroenterologische Funktionsdiagnostik ­ neue Entwicklungen und Tipps für die Praxis.

The functional gastrointestinal disorders (FGIDs) have a high prevalence and are associated with high healthcare costs. The diagnosis of these diseases could be difficult and require func-tional tests such as high-resolution manometry (HRM) of the esophagus, anorectal manometry and H2-Breathtests. Due to the COVID-19 Pandemic and the fear of infections there was a marked reduction in the number of performed exams in the last months - nevertheless some exams are necessary, in order to exclude or to diagnose important and dangerous diseases like Achalasia. Goal of this article is to present some new and relevant developments in the field. The HRM of the esophagus is the diagnostic standard for Achalasia, a rare clinical condi-tion associated to dysphagia - new European guidelines suggests a safe strategy in perform-ing the pneumatic dilatation.The intestinal methanogen overgrowth (IMO) is a clinical condition caused by a high production of methane in the small intestine due to overgrowth of Methanobrevibacter smithii, this condition could be in some patients associated with irritable bowel syndrome.

Cost-effectiveness of rapid on-site evaluation of endoscopic ultrasound fine needle aspiration in gastrointestinal lesions.

BACKGROUND AND AIM: Rapid on-site evaluation (ROSE) can improve adequacy rates of fine needle aspiration (FNA) and thus save operational costs. Our aim was to assess the cost-efficacy of ROSE performed during endoscopic ultrasound (EUS)-FNA of gastrointestinal lesions. METHOD: This was a retrospective cohort study of 156 patients who underwent EUS-FNA for pancreatic, submucosal upper gastrointestinal, and adjacent lesions at Galilee Medical Center between 2012 and 2017. The patient cohort was divided into group A (62 patients, 39.7%) who underwent EUS-FNA with ROSE, and group B (94 patients, 60.3%) without ROSE. Cost analysis was based on the additional expenditure of repeated EUS-FNA sessions needed to reach accurate and final diagnosis in the two groups. RESULTS: The overall cost was significantly higher in group B ($121 422) as compared to group A ($72 861), including the ROSE cost. Additional EUS-FNA sessions were needed in 11.3% and 23.4% in groups A and B, respectively. The additional cost to achieve final pathological diagnosis was $7203 and $24 696 in groups A and B, respectively (P = .02), yielding a savings of $252 per EUS-FNA case by adding ROSE. Notably, adding ROSE to the EUS-FNA exam for gastrointestinal non-pancreatic lesions resulted in even higher savings per case ($682.40). Moreover, adding ROSE improved specimen adequacy to achieve final pathological diagnosis (odds ratio = 7.13, P = .0005). CONCLUSIONS: EUS-FNA with ROSE was cost-effective. Incorporating ROSE into the clinical practice of EUS-FNA saves costs and improves specimen adequacy.

Perceived Barriers to Treatment in Persons Treated for Functional Gastrointestinal Disease with Constipation.

INTRODUCTION: Despite expanding treatment options, patients with functional gastrointestinal disorders (FGID) frequently express concerns about problems with access to care. We hypothesized that health insurance coverage contributes to the perceived problems with care delivery. METHODS: Using the Medical Expenditure Panel Survey, we examined a cohort of participants defined by the diagnosis code for FGID plus the recorded prescription for laxative therapy. Demographic data, healthcare utilization and cost, insurance coverage, comorbid conditions, and information about provider characteristics were extracted for the years 2005-2015. Age- and sex-matched controls were identified for each year included. Barriers to care were based on responses to questions about inability to receive timely care or medication. Logistic regression was used to identify independent predictors of perceived barriers. RESULTS: The cohort was female predominant (67.8%; mean age: 58.8 ± 0.33 years) with 15.4% reporting problems with access to care. Limited insurance coverage was most commonly cited by respondents. Consistent with this result, uninsured persons were significantly more likely to report barriers to care, while the type of insurance for those covered did not independently predict access problems. In addition, comorbidity burden and provider-specific factors, such as available contact options or insufficient explanations, correlated with perceived barriers to care delivery. CONCLUSION: While the study design cannot establish causal links, persons with FGID commonly report access problems, which correlate with lack of health insurance and comorbidities. Providers can influence this perception by offering more flexible office hours and incorporating patient expectations related to treatment explanations and shared decision-making.

Theranostic Gastrointestinal Endoscopy: Bringing Healing Light to the Lumen.

Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a "smart" multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies: "Theranostic gastrointestinal endoscopy." Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.

Utilization of Acid Suppression Medication in an Underserved Population.

OBJECTIVES: Acid suppression therapy (AST), composed of proton pump inhibitors (PPIs), histamine-2 receptor blockers, and antacids, is one of the most common medication groups used in the United States. Long-term AST is concerning, however, because it is linked with an increased risk of community-acquired pneumonia, Clostridium difficile infections, bone fractures, and nutritional deficiencies. The potentially harmful biological and economic consequences associated with the improper use of acid suppression medications presents a great deal of risk to those in underserved communities. We sought to determine the prevalence of AST in an underserved population and the common diagnoses and symptoms associated with therapy. In addition, we studied the frequency of suboptimal usage of PPIs in an indigent care population and the potential factors related to high-risk behaviors. METHODS: The study was a cross-sectional study using a survey that was distributed to participants during their regularly scheduled visits to a public sector provider of health care for low-income patients. RESULTS: Of the 176 participants surveyed, 70 (40%) were using AST. Esophagitis and gastroesophageal reflux disease were the most prevalent in our sample population. PPIs were the most common acid suppression medication used in our population. Of those using PPIs, 85% were never instructed to cease use. Of the 27 patients with PPI prescriptions, 26 used it in a suboptimal manner, and of those without prescriptions, 7 used it in a suboptimal manner. CONCLUSIONS: ASTs are prevalent in low-income populations, and patients are not being managed appropriately to minimize their risk for complications of AST.

Evidence of gut enteropathy and factors associated with undernutrition among slum-dwelling adults in Bangladesh.

BACKGROUND: Adult undernutrition (BMI <18.5 kg/m2) is responsible for immune deficits, increased risk of disease burden, and higher rates of mortality. The prevalence of adult undernutrition in Bangladesh is substantial, but there have been few studies on the etiology of this condition for the inhabitants of urban slums. OBJECTIVE: The aim of this study was to identify the factors associated with undernutrition among slum-dwelling adults in Bangladesh. METHODS: A case-control study was conducted in the Bauniabadh area of Dhaka, Bangladesh. 270 adult participants (135 cases with a BMI <18.5 and 135 controls with a BMI between 18.5 and 24.9) aged 18-45 y were enrolled between October 2018 and January 2019. Sociodemographic variables, dietary diversity, micronutrient deficiencies, psychological symptoms, infection, and biomarkers of gut health were assessed to identify the factors associated with undernutrition using multivariable logistic regression analysis. RESULTS: A higher number of siblings [adjusted odds ratio (aOR): 1.39; 95% CI: 1.11, 1.77], increased self-reporting questionnaire-20 score (an instrument to screen mental health disorders and detect psychological symptoms) (aOR: 1.12; 95% CI: 1.04, 1.23), elevated fecal concentration of α-1 antitrypsin (aOR: 4.82; 95% CI: 1.01, 25.29), and anemia (aOR: 3.63; 95% CI: 1.62, 8.58) were positively associated with undernutrition in adults. Age (aOR: 0.90; 95% CI: 0.84, 0.96), dietary diversity score (aOR: 0.75; 95% CI: 0.56, 0.99), C-reactive protein (aOR: 0.82; 95% CI: 0.73, 0.92), Helicobacter pylori infection (aOR: 0.11; 95% CI: 0.05, 0.23), and always washing hands before eating or preparing foods (aOR: 0.33; 95% CI: 0.12, 0.87) were associated with reduced odds of undernutrition among the study population. CONCLUSIONS: Our results indicate that undernutrition in slum-dwelling adults in Bangladesh is associated with numerous physiological and sociodemographic factors, including evidence of gastrointestinal inflammation and altered intestinal permeability.

Identification of a Short DNA Bar Code in the 18S rDNA for Improved Differentiation of Common Eimeria Species Infecting Chickens.

The coccidian species Eimeria is a parasitic protozoan that causes the gastrointestinal disease coccidiosis in numerous vertebrate species. Incidence of the disease in commercial chickens produces drastic economic losses. Traditionally, detection of Eimeria has been performed using classical methods such as observation of oocyst morphology. However, molecular methods to detect and speciate Eimeria are becoming more prevalent. The 18S ribosomal gene, in particular, has been a widely used DNA amplification target for detection of Eimeria. Although the full-length gene is typically used for this purpose, newer research targeting shorter regions of the gene is being performed. This study investigated the suitability of a 120-base pair (bp) DNA bar code within the 18S gene for species differentiation. When comparing sequence variation from the Eimeria species infecting chickens, shortening the 18S gene to the 120-bp highly variable region provided increased species differentiation, while also reducing intraspecies variation. This DNA bar code is useful for distinction of the Eimeria species infecting chickens and should be considered for future molecular detection assays and metagenomic sequencing.

Functional gastrointestinal disorders in children and adolescents: Knowledge, practice and attitudes of Australian paediatricians.

AIM: To investigate paediatricians' understanding of, and approaches to, the diagnosis and treatment of functional abdominal pain (FAP) and irritable bowel syndrome (IBS) in children. METHODS: This study used an electronic survey of doctors subscribing to a popular Australian-based paediatrics email forum. Responses about investigation and management in two clinical vignettes were correlated with respondent demographic data, practice setting, attitudes and knowledge. RESULTS: The 327 respondents were mostly female (60.3%), aged <45 years (54.5%), general paediatricians (53.5%), working in public outpatient clinics (50.5%). Awareness of Rome III diagnostic criteria was low (37.2%) but associated with confidence in diagnosing FAP/IBS in the vignettes. Respondents who lacked confidence in diagnosing FAP/IBS requested more investigations (P < 0.05), although most acknowledged they would not be helpful. Most (70.5%) believed that families are unlikely to accept an FAP diagnosis without investigations requested. Fewer than 1 of 3 were aware of clear evidence for the effective therapy of FAP or IBS, although awareness did not influence management options selected. Two-thirds of respondents believe that FAP is a psychological rather than a medical problem, while few (8.8%) believe the same about IBS (P < 0.001). Parental pressure to find an immediate cure was cited as the most frequent challenge to successful management in both FAP (86.6%) and IBS (75.9%). CONCLUSIONS: Awareness of the Rome criteria was associated with greater confidence in diagnosing FAP and IBS. Attitudes to FAP and IBS being diagnoses of exclusion are prevalent among paediatricians and associated with more investigations requested. There is a lack of awareness of evidence-based therapies for FAP and IBS.

GI Surgical Emergencies: Scope and Burden of Disease.

Nearly 3 million patients are hospitalized every year for emergent gastrointestinal (GI) surgical problems and nearly one third of those will require surgery. This article reviews the scope of GI surgical emergencies within the context of emergency general surgery (EGS), costs of care, overview of several common GI surgical problems, and traditional and emerging treatment modalities. This article also argues for ongoing work in the area of risk assessment for EGS, and describes quality metrics as well as outcomes of care for these patients.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018.

BACKGROUND & AIMS: Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States. METHODS: We estimated health care use and spending based on the most currently available administrative claims from commercial and Medicare Supplemental plans, data from the GI Quality Improvement Consortium Registry, and national databases. RESULTS: In 2015, annual health care expenditures for gastrointestinal diseases totaled $135.9 billion. Hepatitis ($23.3 billion), esophageal disorders ($18.1 billion), biliary tract disease ($10.3 billion), abdominal pain ($10.2 billion), and inflammatory bowel disease ($7.2 billion) were the most expensive. Yearly, there were more than 54.4 million ambulatory visits with a primary diagnosis for a GI disease, 3.0 million hospital admissions, and 540,500 all-cause 30-day readmissions. There were 266,600 new cases of GI cancers diagnosed and 144,300 cancer deaths. Each year, there were 97,700 deaths from non-malignant GI diseases. An estimated 11.0 million colonoscopies, 6.1 million upper endoscopies, 313,000 flexible sigmoidoscopies, 178,400 upper endoscopic ultrasound examinations, and 169,500 endoscopic retrograde cholangiopancreatography procedures were performed annually. Among average-risk persons aged 50-75 years who underwent colonoscopy, 34.6% had 1 or more adenomatous polyps, 4.7% had 1 or more advanced adenomatous polyps, and 5.7% had 1 or more serrated polyps removed. CONCLUSIONS: GI diseases contribute substantially to health care use in the United States. Total expenditures for GI diseases are $135.9 billion annually-greater than for other common diseases. Expenditures are likely to continue increasing.

Approach to gastroenterological diseases in primary care.

Gastroenterological diseases are a source of morbidity, mortality and costs, and have a high frequency in general practice; for this reason, we have evaluated the current literature regarding the knowledge and management of these disorders by general practitioners, finding little knowledge and adherence to guidelines, highlighting the need for continuous updating in this regard, and greater collaboration between specialists and general practitioners.

Interdisciplinary aerodigestive care model improves risk, cost, and efficiency.

OBJECTIVE: This study sought to evaluate the impact of an interdisciplinary care model for pediatric aerodigestive patients in terms of efficiency, risk exposure, and cost. METHODS: Patients meeting a standard clinical inclusion definition were studied before and after implementation of the aerodigestive program. RESULTS: Aerodigestive patients seen in the interdisciplinary clinic structure achieved a reduction in time to diagnosis (6 vs 150 days) with fewer required specialist consultations (5 vs 11) as compared to those seen in the same institution prior. Post-implementation patients also experienced a significant reduction in risk, with fewer radiation exposures (2 vs 4) and fewer anesthetic episodes (1 vs 2). Total cost associated with the diagnostic evaluation was significantly reduced from a median of $10,374 to $6055. CONCLUSION: This is the first study to utilize a pre-post cohort to evaluate the reduction in diagnostic time, risk exposure, and cost attributable to the reorganization of existing resources into an interdisciplinary care model. This suggests that such a model yields improvements in care quality and value for aerodigestive patients, and likely for other pediatric patients with chronic complex conditions.

Evolution of incidence, mortality and cost of nontraumatic abdominal emergencies treated in Brasil in a period of nine years.

OBJECTIVE: To evaluate the incidence, mortality and cost of non-traumatic abdominal emergencies treated in Brazilian emergency departments. METHODS: This paper used DataSus information from 2008 to 2016 (http://www.tabnet.datasus.gov.br). The number of hospitalizations, costs - AIH length of stay and mortality rates were described in acute appendicitis, acute cholecystitis, acute pancreatitis, acute diverticulitis, gastric and duodenal ulcer, and inflammatory intestinal disease. RESULTS: The disease that had the highest growth in hospitalization was diverticular bowel disease with an increase of 68.2%. For the period of nine years, there were no significant changes in the average length of hospital stay, with the highest increase in gastric and duodenal ulcer with a growth of 15.9%. The mortality rate of gastric and duodenal ulcer disease increased by 95.63%, which is significantly high when compared to the other diseases. All had their costs increased but the one that proportionally had the highest increase in the last nine years was the duodenal and gastric ulcer, with an increase of 85.4%. CONCLUSION: Non-traumatic abdominal emergencies are extremely prevalent. Hence, the importance of having updated and comparative data on the mortality rate, number of hospitalization and cost generated by these diseases to provide better healthcare services in public hospitals.

Economic burden associated with adverse events of special interest in patients with relapsed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia in the United States.

BACKGROUND: Infections, cytopenia, and gastrointestinal (GI) toxicity are adverse events of special interest (AESI) affecting most relapsed Philadelphia chromosome-negative (Ph-) B-cell acute lymphocytic leukemia (ALL) patients. This study quantified real-world rates and economic burden of these events among relapsed Ph- B-cell ALL patients in the United States. METHODS: Adults with relapsed Ph- B-cell ALL during 1 April 2009-31 October 2016 were selected from MarketScan® healthcare claims databases. Outcomes included proportions of patients with AESIs and AESI-related costs during 100 days after relapsed hospitalization. RESULTS: Of 400 relapsed Ph- B-cell ALL patients, 92.5% experienced ≥1 AESI during the median 100-day follow-up, of which 64.6% had infections, 94.6% cytopenia, and 46.2% GI toxicities. Mean (SD; median) AESI-related total cost per patient during follow-up was $197,213 ($308,551; $105,731), with a mean of 2 AESI-related hospitalizations comprising 32.2 inpatient days. Mean (SD; median) healthcare costs were highest for infections ($164,461 [$347,083; $64,528]), followed by cytopenia ($125,210 [$165,141; $67,475]) and GI events ($11,652 [$40,231; $1349]). CONCLUSION: The economic burden of AESIs is substantial, with infections the most expensive, followed by cytopenia and GI toxicity. New therapies that can improve outcomes in relapsed Ph- B-cell ALL while offering a favorable safety profile are needed.

The Cost of Complications Following Major Resection of Malignant Neoplasia.

BACKGROUND: Rising healthcare costs have led to increased focus on the need to achieve a higher "value of care." As value-maximization efforts expand to include more complex surgical patients, evidence to support meaningful implementation of complication-based initiatives is lacking. The objective of this study was to compare incremental costs of complications following major gastrointestinal (GI) resections for organ-specific malignant neoplasia using nationally representative data. METHODS: National (Nationwide) Inpatient Sample data, 2001-2014, were queried for adult (≥ 18 years) patients undergoing major resections for malignant neoplasia. Based on system-based complications considered relevant to the long-term treatment of GI disease, stratified differences in risk-adjusted incremental hospital costs and complication probabilities were compared. Differences in surgical outcomes and costs over time were also assessed. RESULTS: A total of 293,967 patients were included, weighted to represent 1,408,117 patients nationwide. One fourth (26.1%; 95% CI, 25.7-26.4%) experienced ≥ 1 pre-discharge complication (range, 45.3% esophagectomy to 24.0% rectal resection). Resultant annual risk-adjusted incremental hospital costs totaled $540 million nationwide (19.5% of the overall cost of care and an average of $20,900 per patient). Costs varied substantially with both cancer/resection type and complication group, ranging from $76.7 million for colectomies with infectious complications to $0.2 million for rectal resections with urinary complications. For each resection type, infectious ($154.7 million), GI ($85.5 million), and pulmonary ($77.9 million) complications were among the most significant drivers of increased hospital cost. CONCLUSIONS: Quantifying and comparing the impact of complications on an indication-specific level in more complex patients offers an important step toward allowing providers/payers to meaningfully prioritize the design of novel and adaptation of existing value-maximization approaches.

The hidden costs: Identification of indirect costs associated with acute gastrointestinal illness in an Inuit community.

BACKGROUND: Acute gastrointestinal illness (AGI) incidence and per-capita healthcare expenditures are higher in some Inuit communities as compared to elsewhere in Canada. Consequently, there is a demand for strategies that will reduce the individual-level costs of AGI; this will require a comprehensive understanding of the economic costs of AGI. However, given Inuit communities' unique cultural, economic, and geographic contexts, there is a knowledge gap regarding the context-specific indirect costs of AGI borne by Inuit community members. This study aimed to identify the major indirect costs of AGI, and explore factors associated with these indirect costs, in the Inuit community of Rigolet, Canada, in order to develop a case-based context-specific study framework that can be used to evaluate these costs. METHODS: A mixed methods study design and community-based methods were used. Qualitative in-depth, group, and case interviews were analyzed using thematic analysis to identify and describe indirect costs of AGI specific to Rigolet. Data from two quantitative cross-sectional retrospective surveys were analyzed using univariable regression models to examine potential associations between predictor variables and the indirect costs. RESULTS/SIGNIFICANCE: The most notable indirect costs of AGI that should be incorporated into cost-of-illness evaluations were the tangible costs related to missing paid employment and subsistence activities, as well as the intangible costs associated with missing community and cultural events. Seasonal cost variations should also be considered. This study was intended to inform cost-of-illness studies conducted in Rigolet and other similar research settings. These results contribute to a better understanding of the economic impacts of AGI on Rigolet residents, which could be used to help identify priority areas and resource allocation for public health policies and programs.

Preclinical efficacy studies in investigator brochures: Do they enable risk-benefit assessment?

Human protection policies require favorable risk-benefit judgments prior to launch of clinical trials. For phase I and II trials, evidence for such judgment often stems from preclinical efficacy studies (PCESs). We undertook a systematic investigation of application materials (investigator brochures [IBs]) presented for ethics review for phase I and II trials to assess the content and properties of PCESs contained in them. Using a sample of 109 IBs most recently approved at 3 institutional review boards based at German Medical Faculties between the years 2010-2016, we identified 708 unique PCESs. We then rated all identified PCESs for their reporting on study elements that help to address validity threats, whether they referenced published reports, and the direction of their results. Altogether, the 109 IBs reported on 708 PCESs. Less than 5% of all PCESs described elements essential for reducing validity threats such as randomization, sample size calculation, and blinded outcome assessment. For most PCESs (89%), no reference to a published report was provided. Only 6% of all PCESs reported an outcome demonstrating no effect. For the majority of IBs (82%), all PCESs were described as reporting positive findings. Our results show that most IBs for phase I/II studies did not allow evaluators to systematically appraise the strength of the supporting preclinical findings. The very rare reporting of PCESs that demonstrated no effect raises concerns about potential design or reporting biases. Poor PCES design and reporting thwart risk-benefit evaluation during ethical review of phase I/II studies.