Health technology reassessment of non-drug technologies: current practices.

OBJECTIVES: Obsolescence is a natural phase of the lifecycle of health technologies. Given increasing cost of health expenditures worldwide, health organizations have little choice but to engage in health technology reassessment (HTR); a structured, evidence-based assessment of the medical, social, ethical, and economic effects of a technology, currently used within the healthcare system, to inform optimal use of that technology in comparison to its alternatives. This research was completed to identify and summarize international HTR initiatives for non-drug technologies. METHODS: A systematic review was performed using the terms disinvestment, obsolescence, obsolete technology, ineffective, reassessment, reinvestment, reallocation, program budgeting, and marginal analysis to search PubMED, MEDLINE, EMBASE, and CINAHL until November 2011. Websites of organizations listed as members of INAHTA and HTAi were hand-searched for gray literature. Documents were excluded if they were unavailable in English, if the title/abstract was irrelevant to HTR, and/or if the document made no mention of current practices. All citations were screened in duplicate with disagreements resolved by consensus. RESULTS: Sixty full-text documents were reviewed and forty were included. One model for reassessment was identified; however, it has never been put into practice. Eight countries have some evidence of past or current work related to reassessment; seven have shown evidence of continued work in HTR. There is negligible focus on monitoring and implementation. CONCLUSIONS: HTR is in its infancy. Although health technology reassessments are being conducted, there is no standardized approach. Future work should focus on developing and piloting a comprehensive methodology for completing HTR.

Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease.

BACKGROUND: The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease were conflicting and controversial. A meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease. OBJECTIVES: To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease. SEARCH STRATEGY: Studies were selected using the MEDLINE database (1966 to July 2009), abstracts from major gastrointestinal meetings and references from published articles and review. The Cochrane Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. This search strategy was updated using the MEDLINE, EMBASE and the International Pharmaceutical Abstracts databases as well as the Cochrane Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register. SELECTION CRITERIA: Randomized, double-blind, placebo-controlled trials of oral azathioprine or 6-mercaptopurine involving adult patients (> 18 years) with active Crohn's disease were selected for inclusion. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel. MAIN RESULTS: Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms. The odds ratio (OR) of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.43 (95% CI 1.62 to 3.64). This corresponded to a number needed to treat (NNT) of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the OR was 2.06 (95% CI 1.25 to 3.39). Treatment of > 17 weeks resulted in an OR of 2.61 (95% CI 1.69 to 4.03). A steroid sparing effect was seen with an OR of 3.69 (95% CI 2.12 - 6.42), corresponding to a NNTof about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased with active therapy with an odds ratio of 3.44 (95% CI 1.52 to 7.77). The NNT to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14. AUTHORS' CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. Adverse events were more common among patients on active therapy.

Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease.

BACKGROUND: The therapeutic role of 6-mercaptopurine and azathioprine remains controversial due to their perceived relatively slow-acting effect and adverse effects. A meta-analysis was performed to evaluate the efficacy of these agents for the maintenance of remission of quiescent Crohn's disease. OBJECTIVES: To assess the efficacy of azathioprine and 6-mercaptopurine for maintenance of remission in quiescent Crohn's disease. SEARCH STRATEGY: Pertinent studies were selected using the MEDLINE data base (1966-May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease register, as well as abstracts from major gastrointestinal research meetings and references from published articles and review. This search strategy was updated (1998-May 2008) using the MEDLINE, EMBASE and International Pharmaceutical Abstracts databases, the Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register. SELECTION CRITERIA: Randomized, double-blind, placebo-controlled trials of oral azathioprine or 6-mercaptopurine involving adult patients (> 18 years) with quiescent Crohn's disease. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers (EP, MC, LRS) based on the intention to treat principle. Peto odds ratios and 95% confidence intervals for maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined. MAIN RESULTS: Seven trials of azathioprine therapy and one of 6-mercaptopurine were included in the review. Azathioprine and 6-mercaptopurine had a positive effect on maintaining remission. The Peto odds ratio (OR) for maintenance of remission with azathioprine was 2.32 (95% CI 1.55 to 3.49) with a NNT of 6. The Peto OR for maintenance of remission with 6-mercaptopurine was 3.32 (95% CI 1.40 to 7.87) with a of 4. Higher doses of azathioprine improved response. A steroid sparing effect with azathioprine was noted, with a Peto OR of 5.22 (95% CI 1.06 to 25.68) and NNT of 3 for quiescent disease. Withdrawals due to adverse events were more common in patients treated with azathioprine (Peto OR 3.74; 95% CI 1.48 to 9.45, NNH = 20) than with placebo. AUTHORS' CONCLUSIONS: Azathioprine and 6-mercaptopurine are more effective than placebo for maintenance of remission in Crohn's disease. Higher response rates were obtained with azathioprine than 6-mercaptopurine. However, the one study evaluating 6-mercaptopurine used a relatively low dose of the drug. Future studies should look at the effect of higher doses of 6-mercaptopurine. There is weak evidence for a steroid sparing effect with azathioprine treatment.

Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease.

BACKGROUND: The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease were conflicting and controversial. A meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease. OBJECTIVES: To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease. SEARCH STRATEGY: Studies were selected using the MEDLINE database (1966 to July 2009), abstracts from major gastrointestinal meetings and references from published articles and review. The Cochrane Trials Register and the Inflammatory Bowel Disease Review Group Trials Register were also searched. This search strategy was updated using the MEDLINE, EMBASE and the International Pharmaceutical Abstracts databases as well as the Cochrane Register of Controlled Trials and the Cochrane IBD/FBD group Specialized Trials Register. SELECTION CRITERIA: Randomized, double-blind, placebo-controlled trials of oral azathioprine or 6-mercaptopurine involving adult patients (> 18 years) with active Crohn's disease were selected for inclusion. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel. MAIN RESULTS: Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms. The odds ratio (OR) of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.43 (95% CI 1.62 to 3.64). This corresponded to a number needed to treat (NNT) of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the OR was 2.06 (95% CI 1.25 to 3.39). Treatment > 17 weeks increased the OR to 2.61 (95% CI 1.69 to 4.03). A steroid sparing effect was seen with an OR of 3.69 (95% CI 2.12 - 6.42), corresponding to a NNTof about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased with active therapy with an odds ratio of 3.44 (95% CI 1.52 to 7.77). The NNT to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14. AUTHORS' CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The OR of response increases after > 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on active therapy.

Evaluation of educational programs in inflammatory bowel disease.

BACKGROUND: Little is known about the status of patient knowledge in inflammatory bowel disease (IBD) and potential benefit of educational programs. The authors conducted this study to assess 1) the knowledge of IBD of participants attending educational workshops offered to the public and 2) the effect of the workshop on participants' knowledge level. METHODS: Workshops on IBD were offered to the public at nine communities in the United States. Each workshop consisted of a combination of 3 hours of presentations and question-and-answer sessions. Participants, including patients with IBD and their parents, spouses, siblings, friends, and significant others, were asked to complete the Crohn's and Colitis Knowledge Score questionnaires just before (Q1) and immediately after (Q2) the workshop and approximately 3 months later (Q3). The authors scored one point for each correct answer to the 30 questions in the Crohn's and Colitis Knowledge Score. RESULTS: Of the 734 who completed the Q1, 33.7% gave correct answers for questions about IBD complications, 36.2% for treatment, 61.4% for general knowledge, and 64.8% for diet. After the workshop, the proportion for these four knowledge areas increased by 11.0% to 19%. For the participants who completed all of the three questionnaires and answered all the 30 questions (N=59), the mean score was 18 at Q1, 22 at Q2 (p<0.001, Q2 vs. Q1), and 21 at Q3 (p<0.001, Q3 vs. Q1). CONCLUSIONS: The public's general knowledge of IBD is low. Educational programs oriented toward IBD improve participant's knowledge, and the knowledge they acquired is retained for at least 3 months.

Irritable bowel syndrome: are incentives useful for improving survey response rates?

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders. There continues to be a need for community-based research into this condition. Unfortunately, response rates in community-based IBS surveys have typically been very low. In this study, we explore the use of incentives and multiple-response options as a means of increasing survey response rates. The study was conducted in three phases. In an initial phase, no incentive was offered; in the second phase, a 5.00 Canadian dollars incentive was offered; and in the third phase, a 20.00 Canadian dollars incentive was offered. Response rates were higher in the incentive groups: Individual response rates were 57.9%, 72.7%, and 84.7% in the three phases, respectively. A slightly higher estimate of IBS prevalence was obtained in the no incentive group. Selection bias is a possible explanation for this difference. A decision about whether to use incentives must be based on the specific goals of the study.

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province.

BACKGROUND: Surveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery. METHODS: In this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest. RESULTS: A colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70-79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001). CONCLUSIONS: The majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics.

Development and evaluation of a quality score for abstracts.

BACKGROUND: The evaluation of abstracts for scientific meetings has been shown to suffer from poor inter observer reliability. A measure was developed to assess the formal quality of abstract submissions in a standardized way. METHODS: Item selection was based on scoring systems for full reports, taking into account published guidelines for structured abstracts. Interrater agreement was examined using a random sample of submissions to the American Gastroenterological Association, stratified for research type (n = 100, 1992-1995). For construct validity, the association of formal quality with acceptance for presentation was examined. A questionnaire to expert reviewers evaluated sensibility items, such as ease of use and comprehensiveness. RESULTS: The index comprised 19 items. The summary quality scores showed good interrater agreement (intra class coefficient 0.60 - 0.81). Good abstract quality was associated with abstract acceptance for presentation at the meeting. The instrument was found to be acceptable by expert reviewers. CONCLUSION: A quality index was developed for the evaluation of scientific meeting abstracts which was shown to be reliable, valid and useful.

Publication bias in gastroenterological research - a retrospective cohort study based on abstracts submitted to a scientific meeting.

BACKGROUND: The aim of this study was to examine the determinants of publication and whether publication bias occurred in gastroenterological research. METHODS: A random sample of abstracts submitted to DDW, the major GI meeting (1992-1995) was evaluated. The publication status was determined by database searches, complemented by a mailed survey to abstract authors. Determinants of publication were examined by Cox proportional hazards model and multiple logistic regression. RESULTS: The sample included abstracts on 326 controlled clinical trials (CCT), 336 other clinical research reports (OCR), and 174 basic science studies (BSS). 392 abstracts (47%) were published as full papers. Acceptance for presentation at the meeting was a strong predictor of subsequent publication for all research types (overall, 54% vs. 34%, OR 2.3, 95% CI 1.7 to 3.1). In the multivariate analysis, multi-center status was found to predict publication (OR 2.8, 95% CI 1.6-4.9). There was no significant association between direction of study results and subsequent publication. Studies were less likely to be published in high impact journals if the results were not statistically significant (OR 0.5, 95 CI 95% 0.3-0.6). The author survey identified lack of time or interest as the main reason for failure to publish. CONCLUSIONS: Abstracts which were selected for presentation at the DDW are more likely to be followed by full publications. The statistical significance of the study results was not found to be a predictor of publication but influences the chances for high impact publication.

Sucrose Permeability: A Novel Means of Detecting Gastroduodenal Damage Noninvasively.

Asymptomatic damage to the upper gastrointestinal tract is a common problem that may present with life-threatening sequelae such as bleeding. This scenario is especially prevalent in the population that ingest nonsteroidal anti-inflammatory agents (NSAIDs). Currently, there exists no means to screen these patients for the presence or absence of gastroduodenal damage prior to clinical presentation. Endoscopy, which remains the "gold standard" for the detection of upper gastrointestinal damage, is a time consuming technique that requires special expertise and may not be generally available. As such, it is an inappropriate technique for the widespread screening of large populations. It is now recognized that intestinal damage can be detected by determining that intestinal permeability is increased in diseases in that affect the small intestine, such as celiac or Crohn's disease. These methods are relatively simple: The patient ingests nondigestible sugar probes that cross damage mucosa and can be detected in the urine in increased amounts. Over the last several years, we have adapted these concepts for the simple noninvasive detection of gastroduodenal damage and have demonstrated that sucrose is an interesting probe molecule that specifically reports damage from the extreme proximal end of the gastrointestinal tract. In this article we review the data that support this contention and demonstrate the clinical usefulness of this approach for the detection of gastric damage in man.

Irritable bowel syndrome and health-related quality of life: a population-based study in Calgary, Alberta.

BACKGROUND: Little is known about the health-related quality of life (HRQOL) of nonclinical samples of people with irritable bowel syndrome (IBS) in Canada. In a pilot survey, the impact of IBS on HRQOL using a population-based, urban sample was examined. METHODS: A random sample of Calgary residents (18 years of age or older), selected by random digit dialing (n=1521), completed a structured questionnaire including ROME II Criteria and Medical Outcomes Study Short-Form 12-Item Health Survey, version 2 (SF-12v2). The mean scale and summary scores of SF-12v2 for those who did and did not meet ROME II criteria and for those who met ROME II criteria with and without visiting a physician in past three months were determined and compared using multiple regression analyses. RESULTS: Of the 951 households successfully contacted, 590 (62%) were willing to participate, of which 437 (74%) individuals were recruited. One hundred ten IBS cases (81 of which were women) and 327 non-IBS controls (180 of which were women) were identified. All of the eight mean scale scores and the two mean summary scores were significantly lower in people with IBS than in those without, whether or not adjusting for demographics. Forty-four of the 110 IBS cases (40%) sought medical help. Significantly lower mean physical component score and three scale scores (general health, social functioning and role physical) were found in those who sought medical help than in those who did not. CONCLUSIONS: People with IBS experience significant impairment in HRQOL, including both physical and mental well-being. People with IBS who seek medical help report worse physical health than those who do not, but their mental health is no different.

Assessing disease activity and disease activity indices for inflammatory bowel disease.

A crucial step in the development of clinical trials to determine the efficacy of various therapies for inflammatory bowel disease (IBD) has been the creation of activity indices. This article reviews the major components and operating characteristics of clinical activity indices commonly used in randomized, controlled trials of IBD therapy. In addition, the paper provides a brief overview of the developmental requirements for any new index.

Population-based study of the epidemiology of and the risk factors for invasive Staphylococcus aureus infections.

A population-based active-surveillance study of the Calgary Health Region (population, 929,656) was conducted from May 1999 to April 2000, to define the epidemiology of invasive Staphylococcus aureus (ISA) infections. The annual incidence was 28.4 cases/100,000 population; 46% were classified as nosocomial. Infection was most common in people at the extremes of the age spectrum and in males. Several conditions were associated with acquisition of ISA infection, and the highest risk was observed in persons undergoing hemodialysis or peritoneal dialysis and in persons infected with human immunodeficiency virus. Forty-six patients (19%) died. Significant independent risk factors for mortality included positive blood-culture result, respiratory focus, empirical antibiotic therapy, and older age. A higher systolic blood pressure at presentation was associated with reduced case-fatality rate. ISA infections are common, with several definable groups of patients at increased risk for acquisition and death from these infections. This study provides important data on the burden of ISA disease and identifies risk groups that may potentially benefit from preventive efforts.