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Objectives: This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future., Methods: A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry R&D productivity and drug development cost estimates., Results: While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines., Conclusions: The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

Objective: The safety and efficacy of NaP tablets have not been compared with 2L PEG lavage solution. A multicenter, investigator-blinded study was conducted to compare the colon-cleansing efficacy of a new NaP tablet formulation with that of 2L PEG solution plus bisacodyl tablets in adults undergoing colonoscopy., Methods: A total of 481 patients were randomized to receive either 32 tablets (48 g) of NaP or 2L PEG solution plus 4 (20 mg) bisacodyl tablets. Quality of colon cleansing was assessed using a 4-point scale (1 = excellent, 2 = good, 3 = fair, and 4 = inadequate), and the primary efficacy end point was mean overall colon-cleansing score. Safety assessments included recording of adverse events and changes in biochemical tests and vital signs., Results: A total of 411 patients were included in the efficacy analysis. The mean overall and ascending colon-cleansing scores for NaP tablets were significantly better than PEG plus bisacodyl (overall 1.5 vs 1.8, ascending 1.4 vs 1.8, P < 0.0001 for both). Patients treated with NaP tablets experienced significantly fewer adverse events (66%vs 82%, P= 0.0003) and gastrointestinal symptoms (64%vs 79%, P= 0.0001) compared with patients receiving PEG plus bisacodyl. Patients receiving NaP tablets were significantly less likely to experience abdominal distention, abdominal pain, and vomiting than patients receiving PEG plus bisacodyl (P < 0.0012). Transient fluctuations in laboratory parameters were observed in both treatment groups; however, the fluctuations were more common and of greater magnitude in the NaP group particularly in phosphorous, sodium, and potassium., Conclusion: The colon-cleansing efficacy of the new 32-tablet NaP dosing regimen in this study was found to be significantly better than the 2L PEG solution plus bisacodyl tablets regimen. The 32-tablet NaP dosing regimen was associated with fewer adverse events. As expected electrolyte shifts were more common and of greater magnitude in the NaP group compared with the PEG plus bisacodyl group; however, both treatment groups demonstrated significant changes in electrolytes and creatinine.

Objectives: The introduction of new sedative agents as well as a desire for improved patient satisfaction and greater efficiency has changed the practice of endoscopic sedation. This survey was designed to provide national and regional data on endoscopic sedation and monitoring practices within the United States., Methods: A 22-item survey regarding current practices of endoscopy and sedation was mailed to 5,000 American College of Gastroenterology physician members nationwide., Results: A total of 1,353 questionnaires (27.1%) were returned. Respondents performed an average of 12.3 esophagogastroduodenoscopies (EGDs) and 22.3 colonoscopies per wk. Endoscopic procedures were performed within a hospital setting (55.2) more often than at an ambulatory center (35.8%) or private office (8.8%). The vast majority of EGDs and colonoscopies (>98%) were performed with endoscopic sedation. Almost three quarters (74.3%) of the respondents used a narcotic and benzodiazepine for sedation, while propofol was preferred by 25.7%. Sedation practices varied considerably within different geographic regions of the United States. Respondents routinely monitored vital signs and pulse oximetry (99.2% and 98.6%, respectively), and supplemental oxygen was administered to all patients during EGD by 72.7% of endoscopists. Endoscopist satisfaction with sedation was greater among those using propofol than conventional sedation (10 vs 8, p < 0.0001)., Conclusions: During the past 15 yr, the volume of procedures performed by endoscopists in the United States has increased two- to fourfold. Propofol is currently being used for sedation in approximately one quarter of all endoscopies in the United States. The findings from this survey may help in the formulation of updated policies and practice guidelines pertaining to endoscopic sedation.

Objectives: This study aimed to assess the efficacy and safety of endoscopically implanting a nonresorbable biocompatible polymer (Enteryx) in the distal esophagus and proximal gastric cardia for the treatment of gastroesophageal reflux disease (GERD)., Methods: In a prospective, multicenter, international trial, 85 well-controlled GERD patients who were receiving chronic proton pump inhibitor (PPI) therapy underwent Enteryx implantation under fluoroscopic visualization, without general anesthesia. After the procedure, patients were discharged within approximately 2-4 h. Patients were judged to be treatment responders if after implantation they reduced PPI dosage by >/=50%. Follow-up evaluations were conducted at 1, 3, 6, and 12 months and included medication usage, symptoms, quality of life, endoscopy, pH monitoring, manometry, and documentation of adverse events., Results: At 12 months, 80.3% (95% CI = 69.9%-88.3%) of 81 evaluable patients were treatment responders. Of the responders, 87.7% completely discontinued PPIs, and 12.3% reduced PPI dosage by >/=50%. Treatment response was more likely in patients with residual implant volume of >/=5 mL (p = 0.027). Other patient and treatment variables were not predictive. Both GERD heartburn and regurgitation symptom scores significantly improved at 12 months compared with baseline (p < 0.001). There were significant reductions in median supine, upright, and total percent time of esophageal exposure to pH <4. Endoscopically assessed esophagitis grades were unchanged. No serious adverse events were encountered. Transient retrosternal chest pain was experienced by 91.8% of patients. This pain was seldom severe and was typically successfully managed with prescription pain medication., Conclusions: Enteryx implantation allows most patients to discontinue PPI therapy, improves their symptoms, and reduces esophageal acid exposure. The effects of implantation are long-lasting, and morbidity is transient and minimal. The procedure requires basic endoscopic skills and seems to provide a useful option in the effective clinical management of GERD.

Objectives: This prospective, multicenter, single-arm study evaluated the safety and efficacy of the endoscopic implantation of Enteryx, a biocompatible, non-biodegradable liquid polymer for the treatment of GERD., Methods: Eighty-five patients with heartburn symptoms responsive to proton pump inhibitor (PPI) use were enrolled. Inclusion requirements were HRQL score < or = 11 on PPI and > or = 20 off PPI, and 24-hour PH probe with > or = 5% total time at PH < or = 4. Patients with a hiatus hernia > 3 cm, grade 3 or 4 esophagitis, or esophageal motility disorder were excluded. Using a 4-mm needle tipped catheter during standard endoscopy, implants were made in 3-4 quadrants deep into the wall of the cardia. Use of PPI medications, pH-metry, manometry, GERD symptoms, and patient quality of life were assessed over a 6-month follow-up period., Results: At 6 months, PPI use was eliminated in 74% and reduced by > 50% in 10% of patients. The median HRQL score improved from 24.0 pre-implant (baseline off PPIs) to 4.0 at 6 months (p < 0.001). Mean total esophageal acid exposure time was 9.5% pretherapy and 6.7% at 6 months (p < 0.001). Mean LES length increased from 2.0 cm at baseline to 3.0 cm posttherapy (p = 0.003). There were no clinically serious adverse events. Transient mild-to-moderate chest pain commonly occurred after implantation., Conclusions: The endoscopic implantation of Enteryx is a safe and effective therapy for eliminating or decreasing the need for PPI medications, improving GERD symptoms and patient quality of life, and decreasing esophageal acid exposure among patients suffering from GERD.

Although metastases from primary carcinoma of the lung to the small intestine appear to be more common than previously suspected, they rarely produce symptoms. Such metastases may present as bowel perforations. Overt gastrointestinal bleeding has been described only as a prelude to perforation. We describe the case of a 55-yr-old man with carcinoma of the lung that had metastasized to the brain and to the third part of the duodenum. The duodenal metastasis presented with massive upper gastrointestinal hemorrhage. The metastasis was seen to be actively bleeding at endoscopy, and a direct fistula from a branch of the superior mesenteric artery to the third part of the duodenum was shown angiographically. Arterial invasion and destruction by tumor was confirmed at postmortem examination. This complication of metastatic carcinoma of the lung has not been previously described in the English literature.

Villous adenomas occur only rarely in the small intestine and are often associated with malignant changes. Multiple villous adenomas of the small intestine are usually seen only in patients with familial polyposis coli. This is a report of a patient with multiple villous adenomas of the ileum associated with a carcinoma of the cecum which originated from a villous adenoma near the ileocecal valve. There was no evidence of other colonic polyps and no history of familial polyposis coli. It appears that polyposis of the small intestine is a rare clinical entity which cannot often be diagnosed due to difficulty in visualizing this area.

A patient with primary choriocarcinoma of the stomach is reported. Abdominal pain, weight loss, a palpable epigastric mass, and gastrointestinal bleeding are the most common clinical features of this germ cell tumor, making it difficult to distinguish choriocarcinoma from primary adenocarcinoma of the stomach. The unique aspect of this case is the mixed histology of this rare neoplasm, containing both adenomatous and embryonal carcinoma, in addition to the choriocarcinoma. We believe that this unusual tumor probably results from dedifferentiation of primary adenocarcinoma of the stomach. On the average, patients with this disease live less than 2 months from the time of diagnosis, and treatment with combination chemotherapy has not improved the survival.