Browsing by Subject "Research Support as Topic"
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Item Open Access A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design.(Trials, 2014-01) Goswami, Neela D; Tsalik, Ephraim L; Naggie, Susanna; Miller, William C; Horton, John R; Pfeiffer, Christopher D; Hicks, Charles BBackground
The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves.Methods
We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition.Results
The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials.Conclusions
No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology.Item Open Access Challenges facing translational research organizations in China: a qualitative multiple case study.(Journal of translational medicine, 2013-10) Zhou, Laixin; Li, Ying; Bosworth, Hayden B; Ehiri, John; Luo, ChangkunBackground
Translational medicine is attracting much attention worldwide and many translational research organizations (TROs) have been established. In China, translational medicine has developed rapidly, but faces many challenges. This study was aimed at exploring these challenges faced by emerging TROs in China.Method
A qualitative, multiple case study approach was used to assess the challenges faced by TROs in China. Data were collected between May and August 2012.Results
Eight cases were identified. Overall, four themes that characterized TROs in China emerged from analyses: 1. objectives, organizer, and funding resources, 2. participating partners and research teams, 3. management, and 4. achievements. All TROs had objectives related to translating basic discovery to clinic treatment and cultivating translational researchers. In terms of organizer and funding resources, 7 out of 8 TROs were launched only by universities and/or hospitals, and funded mostly through research grants. As for participating partners and multidisciplinary research teams, all but one of the TROs only involved biomedical research institutions who were interested in translational research, and characterized as clinical research centers; 7 out of 8 TROs involved only researchers from biomedicine and clinical disciplines and none involved disciplines related to education, ethnicity, and sociology, or engaged the community. Current management of the TROs were generally nested within the traditional research management paradigms, and failed to adapt to the tenets of translational research. Half of the TROs were at developmental stages defined as infrastructure construction and recruitment of translational researchers.Conclusions
TROs in China face the challenge of attracting sustainable funding sources, widening multidisciplinary cooperation, cultivating multi-disciplinary translational researchers and adapting current research management to translational research. Greater emphasis should be placed on increasing multidisciplinary cooperation, and innovating in education programs to cultivate of translational researchers. Efforts should be made to reform research management in TROs, and establish sustainable funding resources.Item Open Access Compliance with results reporting at ClinicalTrials.gov.(N Engl J Med, 2015-03-12) Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert MBACKGROUND: The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. METHODS: Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. RESULTS: From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. CONCLUSIONS: Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.).Item Open Access Consistency of financial interest disclosures in the biomedical literature: the case of coronary stents.(PLoS One, 2008-05-07) Weinfurt, Kevin P; Seils, Damon M; Tzeng, Janice P; Lin, Li; Schulman, Kevin A; Califf, Robert MBACKGROUND: Disclosure of authors' financial interests has been proposed as a strategy for protecting the integrity of the biomedical literature. We examined whether authors' financial interests were disclosed consistently in articles on coronary stents published in 2006. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed for English-language articles published in 2006 that provided evidence or guidance regarding the use of coronary artery stents. We recorded article characteristics, including information about authors' financial disclosures. The main outcome measures were the prevalence, nature, and consistency of financial disclosures. There were 746 articles, 2985 authors, and 135 journals in the database. Eighty-three percent of the articles did not contain disclosure statements for any author (including declarations of no interests). Only 6% of authors had an article with a disclosure statement. In comparisons between articles by the same author, the types of disagreement were as follows: no disclosure statements vs declarations of no interests (64%); specific disclosures vs no disclosure statements (34%); and specific disclosures vs declarations of no interests (2%). Among the 75 authors who disclosed at least 1 relationship with an organization, there were 2 cases (3%) in which the organization was disclosed in every article the author wrote. CONCLUSIONS/SIGNIFICANCE: In the rare instances when financial interests were disclosed, they were not disclosed consistently, suggesting that there are problems with transparency in an area of the literature that has important implications for patient care. Our findings suggest that the inconsistencies we observed are due to both the policies of journals and the behavior of some authors.Item Open Access Impact of Funding Source on Clinical Trial Results Including Cardiovascular Outcome Trials.(Am J Cardiol, 2015-12-15) Riaz, Haris; Raza, Sajjad; Khan, Muhammad Shahzeb; Riaz, Irbaz Bin; Krasuski, Richard APrevious authors have suggested a higher likelihood for industry-sponsored (IS) studies to have positive outcomes than non-IS studies, though the influence of publication bias was believed to be a likely confounder. We attempted to control for the latter using a prepublication database to compare the primary outcome of recent trials based on sponsorship. We used the "advanced search" feature in the clinicaltrials.gov website to identify recently completed phase III studies involving the implementation of a pharmaceutical agent or device for which primary data were available. Studies were categorized as either National Institutes of Health (NIH) sponsored or IS. Results were labeled "favorable" if the results favored the intervention under investigation or "unfavorable" if the intervention fared worse than standard medical treatment. We also performed an independent literature search to identify the cardiovascular trials as a case example and again categorized them into IS versus NIH sponsored. A total of 226 studies sponsored by NIH were found. When these were compared with the latest 226 IS studies, it was found that IS studies were almost 4 times more likely to report a positive outcome (odds ratio [OR] 3.90, 95% confidence interval [CI] 2.6087 to 5.9680, p <0.0001). As a case example of a specialty, we also identified 25 NIH-sponsored and 215 IS cardiovascular trials, with most focusing on hypertension therapy (31.6%) and anticoagulation (17.9%). IS studies were 7 times more likely to report favorable outcomes (OR 7.54, 95% CI 2.19 to 25.94, p = 0.0014). They were also considerably less likely to report unfavorable outcomes (OR 0.11, 95% CI 0.04 to 0.26, p <0.0001). In conclusion, the outcomes of large clinical studies especially cardiovascular differ considerably on the basis of their funding source, and publication bias appears to have limited influence on these findings.Item Open Access Issues in regulatory guidelines for data monitoring committees.(Clin Trials, 2004) DeMets, David; Califf, Robert; Dixon, Dennis; Ellenberg, Susan; Fleming, Thomas; Held, Peter; Julian, Desmond; Kaplan, Richard; Levine, Robert; Neaton, James; Packer, Milton; Pocock, Stuart; Rockhold, Frank; Seto, Belinda; Siegel, Jay; Snapinn, Steve; Stump, David; Temple, Robert; Whitley, RichardAs clinical trials have emerged as the major research method for evaluating new interventions, the process for monitoring intervention safety and benefit has also evolved. The Data Monitoring Committee (DMC) has become the standard approach to implement this responsibility for many Phase III trials. Recent draft guidelines on the operation of DMCs by the Food and Drug Administration (FDA) have raised issues that need further clarification or discussion, especially for industry sponsored trials. These include, the time when DMCs are needed, the role of the independent statistician to support the DMC, and sponsor participation at DMC meetings. This paper provides an overview of these issues, based on the discussions at the January, 2003 workshop sponsored by Duke Clinical Research Institute.Item Open Access Race disparity in grants: check the citations.(Science (New York, N.Y.), 2011-11) Erickson, Harold PItem Open Access Returns to R&D on new drug introductions in the 1980s.(J Health Econ, 1994-12) Grabowski, HG; Vernon, JMThis study finds that the mean IRR for 1980-84 U.S. new drug introductions is 11.1%, and the mean NPV is 22 million (1990 dollars). The distribution of returns is highly skewed. The results are robust to plausible changes in the baseline assumptions. Our work is also compared with a 1993 study by the OTA. Despite some important differences in assumptions, both studies imply that returns for the average NCE are within one percentage point of the industry's cost of capital. This is much less than what is typically observed in analyses based on accounting data.Item Open Access The distribution of sales revenues from pharmaceutical innovation.(Pharmacoeconomics, 2000) Grabowski, HG; Vernon, JOBJECTIVE: This report updates our earlier work on the returns to pharmaceutical research and development (R&D) in the US (1980 to 1984), which showed that the returns distributions are highly skewed. It evaluates a more recent cohort of new drug introductions in the US (1988 to 1992) and examines how the returns distribution is emerging for drugs with life cycles concentrated in the 1990s versus the 1980s. DESIGN AND SETTING: Methods were described in detail in our earlier reports. The current sample included 110 new drug entities (including 28 orphan drugs), and sales data were obtained for the period 1988 to 1998, which represented between 7 and 11 years of sales for the drugs included. 20 years was chosen as the expected market life for this cohort, and a 2-step procedure was used to project future sales for the drugs--during the period until patent expiry and then beyond patent expiry until the 20-year time-horizon was completed. Thus, the values in the first half of the life cycle are essentially based on realised sales, while those in the second half are projected using information on patent expiry and other inputs. MAIN OUTCOME MEASURES AND RESULTS: Peak annual sales for the top decile of drugs introduced between 1988 and 1992 in the US amounted to almost $US1.1 billion compared with peak sales of less than $US175 million (1992 values) for the mean compound. In particular, the top decile accounted for 56% of overall sales revenue. Although the sales distributions were skewed in both our earlier and current analysis, the top decile in the later time-period exhibited more rapid rates of growth after launch, a peak that was more than 50% greater in real terms than for the 1980 to 1984 cohort, and a faster rate of expected decline in sales after patent expiry. One factor contributing to the distribution of sales revenues becoming more skewed over time is the orphan drug phenomenon (i.e. most of the orphan drugs are concentrated at the bottom of the distribution). CONCLUSION: The distribution of sales revenues for new drug compounds is highly skewed in nature. In this regard, the top decile of new drugs accounts for more than half of the total sales generated by the 1988 to 1992 cohort analysed. Furthermore, the distribution of sales revenues for this cohort is more skewed than that of the 1980 to 1984 cohort we analysed in previous research.Item Open Access The price of innovation: new estimates of drug development costs.(J Health Econ, 2003-03) DiMasi, Joseph A; Hansen, Ronald W; Grabowski, Henry GThe research and development costs of 68 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per new drug is 403 million US dollars (2000 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 11% yields a total pre-approval cost estimate of 802 million US dollars (2000 dollars). When compared to the results of an earlier study with a similar methodology, total capitalized costs were shown to have increased at an annual rate of 7.4% above general price inflation.Item Open Access Trust in Community-Engaged Research Partnerships: A Methodological Overview of Designing a Multisite Clinical and Translational Science Awards (CTSA) Initiative.(Evaluation & the health professions, 2020-09) Kim, Mimi M; Cheney, Ann; Black, Anita; Thorpe, Roland J; Cene, Crystal Wiley; Dave, Guarav J; Schaal, Jennifer; Vassar, Stefanie; Ruktanonchai, Corrine; Frerichs, Leah; Young, Tiffany; Jones, Jennifer; Burke, Jessica; Varma, Deepthi; Striley, Catherine; Cottler, Linda; Brown, Arleen; Sullivan, Greer; Corbie-Smith, GiselleCommunity-engaged research (CEnR) builds on the strengths of the Clinical and Translational Science Awards (CTSA) framework to address health in underserved and minority communities. There is a paucity of studies that identify the process from which trust develops in CEnR partnerships. This study responds to the need for empirical investigation of building and maintaining trust from a multistakeholder perspective. We conducted a multi-institutional pilot study using concept mapping with to better understand how trust, a critical outcome of CEnR partnerships, can act as "social capital." Concept mapping was used to collect data from the three stakeholder groups: community, health-care, and academic research partners across three CTSAs. Concept mapping is a mixed-methods approach that allows participants to brainstorm and identify factors that contribute to a concept and describe ways in which those factors relate to each other. This study offers important insights on developing an initial set of trust measures that can be used across CTSAs to understand differences and similarities in conceptualization of trust among key stakeholder groups, track changes in public trust in research, identify both positive and negative aspects of trust, identify characteristics that maintain trust, and inform the direction for future research.