Non-industry Sponsored Studies Research Articles

Translated consent documents (CDs) and use in non-industry sponsored studies (NISS).

6553 Background: Patients (pts) from historically underrepresented groups often have limited English proficiency (LEP). One challenge specific to obtaining consent from these pts to participate in clinical trials is the need for translated CDs. CD translation leads to enrollment delays and increases costs to study sponsors. We hypothesized that NISS, for which the principal investigator pays translation costs, would consent proportionately fewer pts with a primary language other than English and pts with LEP compared to industry sponsored studies (ISS). Methods: Pts’ primary language and English proficiency were assessed for all 12,082 consent events with appropriate available data at the Jonsson Comprehensive Cancer Center from 2013 to 2018. Pts with LEP were pts (or parent/guardian for pediatric pts) who had a primary language other than English, and the electronic health record indicated that the pt required a translator within 6 months of the consent date. CD language was documented per chart review when available, and when not, languages of available IRB-approved CDs were evaluated. The proportion of consent events for pts with a primary language other than English and with LEP were compared between NISS and ISS using generalized estimating equations, and the odds of signing CDs in the pts primary language were evaluated by multivariable analyses. Discrepant CD language data was evaluated by McNemar’s test. All analyses were performed using SAS 9 (SAS Institute, Cary, NC, USA). Results: Pts with a primary language other than English represented 8.1% of consent events in ISS vs 4.4% in NISS (p<0.001) and 5.5% vs 2.8% (p<0.001) for pts with LEP. Pts with a primary language other than English represented 4.5% vs 1.2% of consent events utilizing CDs in the pts’ primary language in ISS vs NISS (p<0.001) and 3.7% vs 0.9% (p<0.001) for pts with LEP. On multivariable analyses, the odds for pts with a primary language other than English of signing CDs to a NISS was 0.74 (CI, 0.63-0.94, p=0.005), and of signing CDs in their primary language was 0.38 (CI, 0.27-0.52, p<0.001) compared to pts whose primary language was English. The odds for pts with LEP of signing CD to a NISS was 0.74 (CI, 0.58-0.95, p=0.02), and signing CDs in their primary language was 0.35 (CI, 0.25-0.50, p<0.001) compared to pts whose primary language was English. Of 52 pts who signed CDs for both ≥1 NISS and ≥1 ISS, 18 signed in discrepant languages, with 16 of those 18 signing translated CDs for the ISS but not the NISS (p=0.002). Conclusions: Although the role of cost as an effect driver cannot be proven in a retrospective analysis, consistent with our hypothesis, the proportion of consent events utilizing appropriately translated CDs for pts with a primary language other than English and pts LEP was lower in NISS vs ISS, driven by lower odds of signing CDs and lower frequency of signing translated CDs. Approaches that reduce translation costs for investigators should be investigated.

Public reporting of black participation in anti-hypertensive drug clinical trials

Non-Hispanic Black people in the United States have the highest prevalence of essential hypertension. Unfortunately, clinical trials often underrepresent Black patients. We aim to understand whether trial sponsorship type is associated with representation of Black participants in anti-hypertensive drug clinical trials. Then, we contextualize our findings amongst current efforts to improve diversity in clinical research populations. We searched ClinicalTrials.gov in May 2022 for antihypertensive drug trials. Of n=408 trials in our initial search, n=97 (23.77%) met inclusion criteria and were stratified by sponsorship type (industry vs non-industry). Standardized tests of difference were employed to compare characteristics of these trials, and linear regression was used to model change over time. Of 97 trials reporting results from 2010 to 2020, there were minimal differences in the percent of Black patients enrolled in anti-hypertensive clinical trials by sponsorship type. Both industry and non-industry sponsored studies had high rates of non-reporting, with slightly more non-reporting for industry (73.2%) vs non-industry (66.67%) studies. Industry funded studies reported results to ClinicalTrials.gov within 23.3 ± 15.0 months from completing studies, while non-industry funded trials reported within 18.9 ± 10.8 months. Despite Black Americans carrying the highest burden of disease for essential hypertension, they are underrepresented in anti-hypertension clinical trials and their overall participation has decreased between 2010 and 2020. In addition, there is major underreporting of trial participant race. We implore researchers and funders to establish clear, meaningful targets for anti-hypertensive drug trial diversity, and improve transparency in reporting of study characteristics.

Facilitating bias in cost-effectiveness analysis: CHEERS 2022 and the creation of assumption-driven imaginary value claims in health technology assessment

The current standards for health technology cost-effectiveness assessment rest on the creation of lifetime assumption-driven modeled simulations for imaginary pricing and consequent patient access recommendations. A recent BMJ paper reports a detailed assessment of 8,192 cost-effectiveness analyses, concluding that industry-sponsored modeled claims were more likely to publish incremental cost-effectiveness ratios (ICERs) below a USD 50,000 threshold than non-industry sponsored studies, supporting the claim that the product was cost-effective. This is unsurprising; indeed, the opposite can occur with a modeled claim deliberately resulting in ICER is excess of USD 50,000. This methodology is well entrenched with the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 guidance for creating imaginary cost-effectiveness modeled claims ensuring the opportunity for deliberately manipulated cost-effectiveness claims. This overlooks limitations imposed by fundamental measurement, rendering assumption-driven simulations redundant analytical exercises. Manipulation of ICERs and claims for cost-effectiveness are mathematically impossible; including cost-utility thresholds, because the preference or utilities supporting creation of quality-of-life years (QALYs) are ordinal scores. Nevertheless, with the promotion of CHEERS 2022, the belief in imaginary modeled value claims is both facilitated and reinforced. With CHEERS 2022, there is a concerted effort, largely in self-interest, to perpetuate the current belief system. This is a self-defeating strategy. Rather than admitting to the deficiencies of assumption-driven simulated imaginary claims, leaders are maintaining that health system decision makers can ignore standards of normal science and fundamental measurement in value claims for pharmaceutical products. This disregard of standards that are commonplace in the sciences and mainstream social sciences perpetuates the opportunity for self-serving modeled claims; where models are a marketing vehicle leading to sponsored systematic bias in formulary submissions. This supports the need for a NEW START paradigm for health technology assessment, focusing on evaluable single-attribute value claims, meeting the required standards for normal science and fundamental measurement.

Facilitating bias in cost-effectiveness analysis: CHEERS 2022 and the creation of assumption-driven imaginary value claims in health technology assessment.

The current standards for health technology cost-effectiveness assessment rest on the creation of lifetime assumption-driven modeled simulations for imaginary pricing and consequent patient access recommendations. A recent BMJ paper reports a detailed assessment of 8,192 cost-effectiveness analyses, concluding that industry-sponsored modeled claims were more likely to publish incremental cost-effectiveness ratios (ICERs) below a USD 50,000 threshold than non-industry sponsored studies, supporting the claim that the product was cost-effective. This is unsurprising; indeed, the opposite can occur with a modeled claim deliberately resulting in ICER is excess of USD 50,000. This methodology is well entrenched with the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 guidance for creating imaginary cost-effectiveness modeled claims ensuring the opportunity for deliberately manipulated cost-effectiveness claims. This overlooks limitations imposed by fundamental measurement, rendering assumption-driven simulations redundant analytical exercises. Manipulation of ICERs and claims for cost-effectiveness are mathematically impossible; including cost-utility thresholds, because the preference or utilities supporting creation of quality-of-life years (QALYs) are ordinal scores. Nevertheless, with the promotion of CHEERS 2022, the belief in imaginary modeled value claims is both facilitated and reinforced. With CHEERS 2022, there is a concerted effort, largely in self-interest, to perpetuate the current belief system. This is a self-defeating strategy. Rather than admitting to the deficiencies of assumption-driven simulated imaginary claims, leaders are maintaining that health system decision makers can ignore standards of normal science and fundamental measurement in value claims for pharmaceutical products. This disregard of standards that are commonplace in the sciences and mainstream social sciences perpetuates the opportunity for self-serving modeled claims; where models are a marketing vehicle leading to sponsored systematic bias in formulary submissions. This supports the need for a NEW START paradigm for health technology assessment, focusing on evaluable single-attribute value claims, meeting the required standards for normal science and fundamental measurement.

Industry sponsorship bias in cost effectiveness analysis: registry based analysis

ObjectiveTo assess the association between industry sponsorship (drug, medical device, and biotechnology companies) and cost effectiveness results in cost effectiveness analysis (CEA).DesignRegistry based analysisData sourceThe Tufts Cost-Effectiveness Analysis Registry was...

Cost of consent document (CD) translation is a potential barrier to consenting limited English-proficient participants (LEPPs) in non-industry–sponsored studies (NISS).

6533 Background: Racial/ethnic minority patients (pts) are underrepresented in cancer clinical trials. Challenges specific to LEPPs include the need for translated CDs, which can cause research delays and add cost. While most enrollment barriers are similar between industry sponsored studies (ISS) and NISS, costs of CD translation are typically covered by the sponsor in ISS. NISS often have limited, or no funds allocated for CD translation. Although it is required that LEPPs sign translated CDs, we hypothesized that investigators on NISS would find ways to avoid incurring the cost of CD translation. Methods: All pts who consented to studies at the UCLA Jonsson Comprehensive Cancer Center from 2013-2018 were included. Electronic health record data was reviewed. Adult LEPPs had a primary language other than English and their chart either flagged them as needing an interpreter or the pt used an interpreter in their care 6 months before or after the consent date. For pediatric patients, regardless of the pt’s primary language, LEPPs had a guardian who needed an interpreter within 6 months of the consent date. CD language was documented when available by chart review, but when not, we evaluated all IRB-approved CDs for the corresponding study and assumed that the pt signed appropriately translated CDs if available at the time of consent or within the following month. Chi square tests were used to compare the proportion of LEPPs who consented to NISS vs ISS and the proportion of LEPPs who consented with CDs not in their primary language. All analyses were performed using JMP, Version 16. SAS Institute Inc., Cary, NC, 1989–2021. Results: Although we do not have access to data on to whom consents were offered, of the 12202 consenting events during the study period, the proportion of consenting events for LEPPs was 2.7% in NISS vs 5.4% for ISS (p < 0.01). This difference did not appear to be driven by study type, as results were similar when only consenting events for interventional studies (n = 9886) were considered, with LEPPs representing 2.4% in NISS vs 5.5% in ISS (p < 0.01). Among LEPPs, 67.2% of participants who consented to NISS consented with CDs in a language other than their primary language vs 32.2% in ISS (p < 0.01). LEPPs who consented with language appropriate CDs represented 0.9% of those consenting to NISS vs 3.7% for ISS (p < 0.01). Conclusions: LEPPs consented less frequently to NISS compared to ISS, and when they did consent to NISS, the CDs were usually not translated into the pt’s primary language. We posit that the cost of translating CD discourages investigators from consenting LEPPs to NISS. Approaches that reduce or eliminate translation costs should increase the availability of translated CDs, potentially increasing enrollment of LEPPs to NISS while ensuring that they are fully informed about the purpose, procedures, and risks involved in these trials.

Industry sponsorship and research outcome: systematic review with meta-analysis.

Clinical research is widely sponsored by drug and device companies. We investigated whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. This review is an update of a previous Cochrane review. In this update we searched MEDLINE and Embase (2010 to February 2015), Cochrane Methodology Register (2015, Issue 2) and Web of Science (June 2015). We included empirical studies that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. Two assessors included papers, extracted data and assessed risk of bias. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether conclusions agreed with results. We included 27 additional papers in this update (review now includes 75 papers). Industry sponsored studies more often had favorable efficacy results, RR: 1.27 (95% CI 1.17-1.37), no difference in harms results RR: 1.37 (95% CI 0.64-2.93) and more often favorable conclusions RR: 1.34 (95% CI 1.19-1.51) compared with non-industry sponsored studies. Nineteen papers reported on sponsorship and efficacy effect size, but could not be pooled due to differences in reporting of data and heterogeneity of results. Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.25 (95% CI 1.05-1.50), compared with non-industry sponsored studies. Drug and device studies sponsored by manufacturing companies have more favorable efficacy results and conclusions than studies sponsored by other sources.

Milk Options Observation (MOO): A Mixed-Methods Study of Chocolate Milk Removal on Beverage Consumption and Student/Staff Behaviors in a Rural Elementary School.

Providing flavored milk in school lunches is controversial, with conflicting evidence on its impact on nutritional intake versus added sugar consumption and excess weight gain. Nonindustry-sponsored studies using individual-level analyses are needed. Therefore, we conducted this mixed-methods study of flavored milk removal at a rural primary school between May and June 2012. We measured beverage selection/consumption pre- and post-chocolate milk removal and collected observation field notes. We used linear and logistic mixed models to assess beverage waste and identified themes in staff and student reactions. Our analysis of data from 315 unique students and 1,820 beverages choices indicated that average added sugar intake decreased by 2.8 g postremoval, while average reductions in calcium and protein consumption were negligible (12.2 mg and 0.3 g, respectively). Five thematic findings emerged, including concerns expressed by adult staff about student rebellion following removal, which did not come to fruition. Removing flavored milk from school-provided lunches may lower students' daily added sugar consumption without considerably decreasing calcium and protein intake and may promote healthy weight.

Industry sponsorship and research outcome.

Clinical research affecting how doctors practice medicine is increasingly sponsored by companies that make drugs and medical devices. Previous systematic reviews have found that pharmaceutical-industry sponsored studies are more often favorable to the sponsor's product compared with studies with other sources of sponsorship. A similar association between sponsorship and outcomes have been found for device studies, but the body of evidence is not as strong as for sponsorship of drug studies. This review is an update of a previous Cochrane review and includes empirical studies on the association between sponsorship and research outcome. To investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. In this update we searched MEDLINE (2010 to February 2015), Embase (2010 to February 2015), the Cochrane Methodology Register (2015, Issue 2) and Web of Science (June 2015). In addition, we searched reference lists of included papers, previous systematic reviews and author files. Cross-sectional studies, cohort studies, systematic reviews and meta-analyses that quantitatively compared primary research studies of drugs or medical devices sponsored by industry with studies with other sources of sponsorship. We had no language restrictions. Two assessors screened abstracts and identified and included relevant papers. Two assessors extracted data, and we contacted authors of included papers for additional unpublished data. Outcomes included favorable results, favorable conclusions, effect size, risk of bias and whether the conclusions agreed with the study results. Two assessors assessed risk of bias of included papers. We calculated pooled risk ratios (RR) for dichotomous data (with 95% confidence intervals (CIs)). Twenty-seven new papers were included in this update and in total the review contains 75 included papers. Industry sponsored studies more often had favorable efficacy results, RR: 1.27 (95% CI: 1.17 to 1.37) (25 papers) (moderate quality evidence), similar harms results RR: 1.37 (95% CI: 0.64 to 2.93) (four papers) (very low quality evidence) and more often favorable conclusions RR: 1.34 (95% CI: 1.19 to 1.51) (29 papers) (low quality evidence) compared with non-industry sponsored studies. Nineteen papers reported on sponsorship and efficacy effect size, but could not be pooled due to differences in their reporting of data and the results were heterogeneous. We did not find a difference between drug and device studies in the association between sponsorship and conclusions (test for interaction, P = 0.98) (four papers). Comparing industry and non-industry sponsored studies, we did not find a difference in risk of bias from sequence generation, allocation concealment, follow-up and selective outcome reporting. However, industry sponsored studies more often had low risk of bias from blinding, RR: 1.25 (95% CI: 1.05 to 1.50) (13 papers), compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.83 (95% CI: 0.70 to 0.98) (six papers). Sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.

The relationship between study sponsorship, risks of bias, and research outcomes in atrazine exposure studies conducted in non-human animals: Systematic review and meta-analysis

BackgroundA critical component of systematic review methodology is the assessment of the risks of bias of studies that are included in the review. There is controversy about whether funding source should be included in a risk of bias assessment of animal toxicology studies. ObjectiveTo determine whether industry research sponsorship is associated with methodological biases, the results, or conclusions of animal studies examining the effect of exposure to atrazine on reproductive or developmental outcomes. MethodsWe searched multiple electronic databases and the reference lists of relevant articles to identify original research studies examining the effect of any dose of atrazine exposure at any life stage on reproduction or development in non-human animals. We compared methodological risks of bias, the conclusions of the studies, the statistical significance of the findings, and the magnitude of effect estimates between industry sponsored and non-industry sponsored studies. ResultsFifty-one studies met the inclusion criteria. There were no differences in methodological risks of bias in industry versus non-industry sponsored studies. 39 studies tested environmentally relevant concentrations of atrazine (11 industry sponsored, 24 non-industry sponsored, 4 with no funding disclosures). Non-industry sponsored studies (12/24, 50.0%) were more likely to conclude that atrazine was harmful compared to industry sponsored studies (2/11, 18.1%) (p value=0.07). A higher proportion of non-industry sponsored studies reported statistically significant harmful effects (8/24, 33.3%) compared to industry-sponsored studies (1/11; 9.1%) (p value=0.13). The association of industry sponsorship with decreased effect sizes for harm outcomes was inconclusive. ConclusionOur findings support the inclusion of research sponsorship as a risk of bias criterion in tools used to assess risks of bias in animal studies for systematic reviews. The reporting of other empirically based risk of bias criteria for animal studies, such as blinded outcome assessment, randomization, and all animals included in analyses, needs to improve to facilitate the assessment of studies for systematic reviews.

Persistent Axial Neck Pain after Cervical Disc Arthroplasty

Introduction There are relatively few, non-industry sponsored studies examining the outcomes and complications of cervical disc arthroplasty (CDA). In addition, there is very little literature examining optimal radiographic parameters for placement of CDA. Therefore, we set out to perform a single-center evaluation of the radiographic outcomes and association with complications following CDA. Methods We performed a retrospective review from August 2008 to August 2012 of all patients from a single military tertiary medical center undergoing cervical disc arthroplasty. Preoperative, immediate postoperative, and final follow-up films were evaluated. The clinical outcomes and complications associated with the procedure were also examined. Results A total of 312 patients were included in the review, with an average radiographic follow-up of 14 months and a 15.1% rate of persistent axial neck pain. For patients with persistent neck pain, the rates of heterotopic ossification (HO) formation and osteolysis were 27.7% and 14.9%, respectively, while the rates were significantly lower for patients without neck pain (12.8% and 6.2%, respectively, p = 0.01). There were no differences in preoperative facet arthrosis, pre- or postoperative disc height, segmental range of motion, or placement of the device relative to the posterior edge of the vertebral body. However, patients with implants more centered between the uncovertebral joints were more likely to experience posterior neck pain ( p =0.03). Conclusions We found that posterior, axial neck pain is relatively frequent after cervical disc arthroplasty, and patients with persistent neck pain were significantly more likely to develop heterotopic ossification or implant-related osteolysis. We also found that patients with implants that were placed off-centered were less likely to also complain of neck pain, though the reasons for this finding are unclear.

Industry sponsorship and publication bias among animal studies evaluating the effects of statins on atherosclerosis and bone outcomes: a meta-analysis.

BackgroundThe effect that sponsorship has on publication rates or overall effect estimates in animal studies is unclear, though methodological biases are prevalent in animal studies of statins and there may be differences in efficacy estimates between industry and non-industry sponsored studies. In the present analysis, we evaluated the impact of funding source on publication bias in animal studies estimating the effect of statins on atherosclerosis and bone outcomes.MethodsWe conducted two independent systematic reviews and meta-analyses identifying animal studies evaluating the effect of statins on reducing the risk of atherosclerosis outcomes (n = 49) and increasing the likelihood of beneficial bone outcomes (n = 45). After stratifying the included studies within each systematic review by funding source, three separate analyses were employed to assess publication bias in these meta-analyses—funnel plots, Egger’s Linear Regression, and the Trim and Fill methods.ResultsWe found potential evidence of publication bias, primarily in non-industry sponsored studies. In all 3 assessments of publication bias, we found evidence of publication bias in non-industry sponsored studies, while in industry-sponsored studies publication bias was not evident in funnel plots and Egger’s regression tests. We also found that inadequate reporting of sponsorship in animal studies is still exceedingly common.ConclusionsIn meta-analyses assessing the effects of statins on atherosclerosis and bone outcomes in animal studies, we found evidence of publication bias, though small numbers of industry-sponsored studies limit the interpretation of the trim-and-fill results. This publication bias is more prominent in non-industry sponsored studies. Industry and non-industry funded researchers may have different incentives for publication. Industry may have a financial interest to publish all preclinical animal studies to maximize the success of subsequent trials in humans, whereas non-industry funded academics may prefer to publish high impact statistically significant results only. Differences in previously published effect estimates between industry- and non-industry sponsored animal studies may be partially explained by publication bias.Electronic supplementary materialThe online version of this article (doi:10.1186/s12874-015-0008-z) contains supplementary material, which is available to authorized users.

Spine device clinical trials: design and sponsorship

Background contextMulticenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. PurposeTo determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Study designAnalysis of data from a publicly available clinical trials database. MethodsClinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. ResultsOne thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term “spine.” Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1–16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8–21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. ConclusionsMost device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose.

Outcomes following cervical disc arthroplasty: A retrospective review

Cervical disc arthroplasty has emerged as a viable technique for the treatment of cervical radiculopathy and myelopathy, with the proposed benefit of maintenance of segmental range of motion. There are relatively few, non-industry sponsored studies examining the outcomes and complications of cervical disc arthroplasty. Therefore, we set out to perform a single center evaluation of the outcomes and complications of cervical disc arthroplasty. We performed a retrospective review of all patients from a single military tertiary medical center undergoing cervical disc arthroplasty from August 2008 to August 2012. The clinical outcomes and complications associated with the procedure were evaluated. A total of 219 consecutive patients were included in the review, with an average follow-up of 11.2 (±11.0)months. Relief of pre-operative symptoms was noted in 88.7% of patients, and 92.2% of patients were able to return to full pre-operative activity. There was a low rate of complications related to the anterior cervical approach (3.2% with recurrent laryngeal nerve injury, 8.9% with dysphagia), with no device/implant related complications. Symptomatic cervical radiculopathy is a common problem in both the civilian and active duty military populations and can cause significant disability leading to loss of work and decreased operational readiness. There exist several surgical treatment options for appropriately indicated patients. Based on our findings, cervical disc arthroplasty is a safe and effective treatment for symptomatic cervical radiculopathy and myelopathy, with a low incidence of complications and high rate of symptom relief.

Post market Research of Oral Anti-Diabetic Drugs: Metformin, Glipizide, and Pioglitazone

The aims of this study were to document the post market research of the pharmaceutical industry and the effects of labeling revisions on post market studies and outcomes of oral anti-diabetics. A literature search identified post market studies of metformin, glipizide, and pioglitazone. Labeling revisions in MedWatch® were collected as indicators of the FDA’s response to post market drug safety. Data were analyzed by comparing industry and non industry sponsored studies for the number of pre- and post-market studies, study sponsorship, drug labeling revisions, and outcomes after the drugs became generic. The number of industry versus non-industry sponsored studies was 149 (49%) and 155 (51%) for metformin; 33 (44%) and 42 (56%) for glipizide; and 85 (80.2%) versus 21 (19.8%) for pioglitazone. The differences in favorable results between industry and non-industry sponsored studies were similar for metformin and glipizide. The number of industry-sponsored studies with favorable results did not significantly increase after metformin or glipizide became generic. Studies sponsored by the manufacturer of glipizide reported significantly more favorable outcomes in comparison to studies sponsored by industry competitors (90% favorable, 10% neutral, 0% unfavorable, P < 0.05). For pioglitazone, significantly more favorable results were reported in industry-sponsored studies (88.2%) as compared to non-industry (66.7%) (p = 0.008) sponsored studies. A significant correlation exists between the number of pioglitazone’s labeling revisions and the number of post market studies (p = 0.008). Post market research is guided by the pharmaceutical industry and by individual researchers’ interests. Pharmaceutical industry-sponsored studies support the favorable use of the patented drug and show unfavorable results of the generic equivalent. A possible correlation exists between drug labeling revisions and the number of post market studies.

Conflict of interest in diabetes research

Conflict of interest in diabetes research

Trends in the application of dynamic allocation methods in multiarm cancer clinical trials

6550 Background: In multiarm oncology clinical trials there is always a risk that the treatment groups could be imbalanced for a prognostic factor, potentially biasing treatment comparisons and compromising the validity of the results. Stratified randomization (SR) is frequently used to reduce imbalances. Dynamic allocation (DA), also known as minimization, is a controversial and largely nonrandom method of treatment allocation that can incorporate more prognostic factors than traditional SR methods. Proponents argue that results from clinical trials implementing DA are potentially more credible, while opponents claim there is little added benefit, increased complexity, and the statistical properties are not fully understood. We reviewed multi-arm cancer trials published between 1995–2005 to describe trends in the application of DA methods. Methods: 476 clinical trials with at least 100 patients in each arm, published in 13 major journals were reviewed. Manuscripts were grouped by impact factor (IF) of the publishing journal into low (&lt;10), medium (10–20) and high (20+) categories. Trial-specific factors associated with publication were collected along with details of allocation method. Results: 112 (24%) trials described using DA for assigning patients to treatment. 79% of trials employing DA methods included 3 or more stratification factors, compared with only 36% of other trials (p &lt; 0.001). Reported use of DA was similar between industry and non-industry sponsored studies (p = 0.85) and by geographical region (p = 0.73). Of 364 trials which did not describe using DA, 103 (28%) reported using SR, but a statement describing stratification on at least one factor was included in 291 (80%) trials. A trend was observed that reported use of both DA (p = 0.072) and SR (p = 0.067) methods increased over time. DA was associated with publication in higher IF journals univariately (OR = 1.67, 95% CI 1.11–2.52, p=0.014) and after adjusting for identified prognostic factors (OR = 1.70, 95% CI 1.06–2.73, p = 0.028). No association between SR and higher IF journal publication was observed (p = 0.52 univariately and p = 0.44 adjusting for other factors). Conclusions: DA is frequently used in cancer clinical trials. Reported use of DA, but not SR, is associated with publication in high IF journals. No significant financial relationships to disclose.

Opinions on registering trial details: a survey of academic researchers

BackgroundThe World Health Organization (WHO) has established a set of items related to study design and administrative information that should build the minimum set of data in a study register. A more comprehensive data set for registration is currently developed by the Ottawa Group. Since nothing is known about the attitudes of academic researchers towards prospective study registration, we surveyed academic researchers about their opinion regarding the registration of study details proposed by the WHO and the Ottawa Group.MethodsThis was a web-based survey of academic researchers currently running an investigator-initiated clinical study which is registered with clinicaltrials.gov. In July 2006 we contacted 1299 principal investigators of clinical studies by e-mail explaining the purpose of the survey and a link to access a 52-item questionnaire based on the proposed minimum data set by the Ottawa Group. Two reminder e-mails were sent each two weeks apart. Association between willingness to disclose study details and study phase was assessed using the chi-squared test for trend. To explore the potential influence of non-response bias we used logistic regression to assess associations between factors associated with non-response and the willingness to register study details.ResultsOverall response was low as only 282/1299 (22%) principal investigators participated in the survey. Disclosing study documents, in particular the study protocol and financial agreements, was found to be most problematic with only 31% of respondents willing to disclose these publicly. Consequently, only 34/282 (12%) agreed to disclose all details proposed by the Ottawa Group. Logistic regression indicated no association between characteristics of non-responders and willingness to disclose details.ConclusionPrincipal investigators of non-industry sponsored studies are reluctant to disclose all data items proposed by the Ottawa Group. Disclosing the study protocol and financial agreements was found to be most problematic. Future discussions on trial registration should not only focus on industry but also on academic researchers.