Cost-effective recruitment methods for a large randomised trial in people with diabetes: A Study of Cardiovascular Events iN Diabetes (ASCEND).

BACKGROUND: Clinical trials require cost-effective methods for identifying, randomising, and following large numbers of people in order to generate reliable evidence. ASCEND (A Study of Cardiovascular Events iN Diabetes) is a randomised '2 × 2 factorial design' study of aspirin and omega-3 fatty acid supplements for the primary prevention of cardiovascular events in people with diabetes; this study used central disease registers and a mail-based approach to identify, randomise, and follow 15,000 people. In collaboration with UK consultants and general practitioners (GPs), researchers identified potentially eligible people with diabetes from centrally held registers (e.g. for retinopathy screening) and GP-held disease registers. Permission was obtained under section 251 of the National Health Service Act 2006 (previously section 60 of the NHS act 2001) to allow invitation letters to be generated centrally in the name of the holder of the register. In addition, with the collaboration of the National Institutes for Health Research (NIHR) Diabetes and Primary Care Research Networks (DRN and PCRN), general practices sent pre-assembled invitation packs to people with a diagnosis of diabetes. Invitation packs included a cover letter, screening questionnaire (with consent form), information leaflet, and a Freepost envelope. Eligible patients entered a 2-month, pre-randomisation, run-in phase on placebo tablets and were only randomised if they completed a randomisation form and remained willing and eligible at the end of the run-in. Follow-up is ongoing, using mail-based approaches that are being supplemented by central registry data. RESULTS: Information on approximately 600,000 people listed on 58 centrally held diabetes registers was obtained, and 300,188 potentially eligible patients were invited to join the study. In addition, 785 GP practices mailed invitations to 120,875 patients. A further 2,340 potential study participants were identified via other routes. In total, 423,403 people with diabetes were invited to take part; 26,462 entered the 2-month, pre-randomisation, run-in phase; and 15,480 were randomised. CONCLUSION: If sufficient numbers of potentially eligible patients can be identified centrally and the trial treatments do not require participants to attend clinics, the recruitment and follow-up of patients by mail is feasible and cost-effective. Wider use of these methods could allow more, large, randomised trials to be undertaken successfully and cost-effectively. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN60635500 , registered on 14 July 2005.

Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development.

There is a pressing need to address the current major gaps in epilepsy treatment, in particular drug-resistant epilepsy, antiepileptogenic therapies, and comorbidities. A major concern in the development of new therapies is that current preclinical testing is not sufficiently predictive for clinical efficacy. Methodologic limitations of current preclinical paradigms may partly account for this discrepancy. Here we propose and discuss a strategy for implementing a "phase II" multicenter preclinical drug trial model based on clinical phase II/III studies designed to generate more rigorous preclinical data for efficacy. The goal is to improve the evidence resulting from preclinical studies for investigational new drugs that have shown strong promise in initial preclinical "phase I" studies. This should reduce the risk for expensive clinical studies in epilepsy and therefore increase the appeal for funders (industry and government) to invest in their clinical development.

The international translational regenerative medicine center.

The International Translational Regenerative Medicine Center, an organizing sponsor of the World Stem Cell Summit 2012, is a global initiative established in 2011 by founding partners Karolinska Institutet (Stockholm, Sweden) and Beckman Research Institute at City of Hope (CA, USA) with a mission to facilitate the acceleration of translational research and medicine on a global scale. Karolinska Institutet, home of the Nobel Prize in Medicine or Physiology, is one of the most prestigious medical research institutions in the world. The Beckman Research Institute/City of Hope is ranked among the leading NIH-designated comprehensive cancer research and treatment institutions in the USA, has the largest academic GMP facility and advanced drug discovery capability, and is a pioneer in diabetes research and treatment.

Research funding at colleges of osteopathic medicine in the United States.

CONTEXT: Research is a vital component of a college of osteopathic medicine (COM) portfolio. Previous studies have described research activity at COMs from 1989 through 2004 using data from surveys of COM administrators conducted by the American Association of Colleges of Osteopathic Medicine (AACOM). However, these studies had limitations. OBJECTIVES: To address the limitations of previous studies and to provide more depth of understanding regarding research activity at COMs by (1) documenting changes in research funding at COMs from 2004 to 2009 according to the funding agencies, principal investigators' degrees, and areas of study after considering inflation and (2) examining predictors of research funding at COMs. METHODS: Information about 2004 and 2009 active research grants and contracts, research expenditures, and COM characteristics was obtained from AACOM databases. Descriptive statistics are presented for 20 COMs that completed the survey in both years. The 2004 dollar values were adjusted for the rate of inflation (13.57%). Bivariate and multivariate analyses were used to explore associations between school characteristics (eg, number of faculty), research expenditures, and research funding outcomes (total amount and number of awards) for all COMs completing the survey in 2009 (n=26). RESULTS: From 2004 to 2009, the total amount of awards increased from 115.2 million to 216.6 million, and the number of awards increased from 450 to 665. Funding rose substantially from foundations (336%), to PhD-DO principal investigators (909%), and for osteopathic manipulative medicine (60%). Total award amounts were positively associated with both research expenditures (P<.001) and the number of faculty (P<.001). Larger research expenditures also were related to securing a greater number of awards (P<.001). CONCLUSION: Research activity at COMs continues to advance partly because of investments in research and faculty made by COMs.

Economic benefits of sponsored clinical trials on pharmaceutical expenditures at a medical center in Taiwan.

Concerns exist regarding the additional cost of patient care when patients are enrolled in clinical trials at hospitals. To assess the avoidance of drug costs by conducting sponsored clinical trials, a retrospective analysis evaluating drug cost avoidance in all sponsored clinical trials was conducted in 2008 at the most prominent medical center in Taiwan. The National Health Insurance (NHI) reimbursement prices of either the investigated drugs or the standardized drug therapy for each specific disease were used to calculate the cost avoidance. Drug cost avoidance from sponsored clinical trials per year, per trial, per patient, in different therapeutic areas, and in different phases was analyzed. Three quarters of the cost avoidance in drug expenditures from 194 sponsored clinical trials were estimated. All cost values are in US Dollars. Around $11.2 million was avoided at the center in 2008. The average value of cost avoidance was $58,000/trial-year or $3,900/participant-year. The early-phase trials and phase III trials accounted for 25% and 56% of all trials, respectively, while they constituted 32% and 49% of the total costs avoided, respectively. The most frequently conducted and highest cost-avoiding trials were those for antineoplastic agents, especially targeted therapy which accounted for 85% of the total cost avoidance of anti-cancer trials. This study demonstrates the profoundly positive economic impact on the healthcare system in Taiwan by sponsored clinical trials. To understand the trend of economic benefits of the trials on pharmaceutical expenditure, it would be important to analyze the cost avoidance of trials regularly in an institution.

Impact of supplemental site grants to increase African American accrual for the Selenium and Vitamin E Cancer Prevention Trial.

BACKGROUND: African American accrual to prevention trials at rates representative of the disease burden experienced by this population requires additional resources and focused efforts. PURPOSE: To describe the rationale, context, and criteria for selection of sites that received Minority Recruitment Enhancement Grants (MREGs) to increase African American recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). To determine if African American accrual was higher among the 15 MREG sites when compared with similar nonawarded sites. METHODS: Changes in African American accrual at sites that received MREGs are compared with changes in a group of 15, frequency-matched, nonawarded sites using a quasi-experimental, post hoc analysis. Successful and unsuccessful recruitment strategies reported by the MREG sites are described. RESULTS: The increased number of African American participants accrued per month at MREG sites post-funding was higher than the change at comparison sites by a factor of 3.38 (p = 0.004, 95% CI: 1.51-7.57). An estimated 602 additional African American participants were recruited at MREG sites due to MREG funding, contributing to the overall 14.9% African American recruitment. Successful recruitment strategies most reported by MREG sites included increasing staff, transportation resources, recruiting through the media, mailings, and prostate cancer screening clinics during off-hours. LIMITATIONS: Comparison sites were chosen retrospectively, not by randomization. Although comparison sites were selected to be similar to MREG sites with regard to potential confounding factors, it is possible that unknown factors could have biased results. Cost-effective analyses were not conducted. CONCLUSIONS: MREG sites increased African American accrual in the post-funding period more than comparison sites, indicating MREG funding enhanced the sites' abilities to accrue African American participants. Targeted grants early in the accrual period may be a useful multi-site intervention to increase African American accrual for a prevention study where adequate African American representation is essential.

A decade of NHMRC People Support expenditure in review: is support for Indigenous health research increasing?

OBJECTIVE: To investigate National Health and Medical Research Council (NHMRC) support over the decade to 2006 for researchers studying Indigenous health and researchers who self-identified as Indigenous. DESIGN AND SETTING: Review of data on all recipients of People Support awards and Capacity Building Grants in Population Health Research who were researching Indigenous health or who self-identified as Indigenous between 1996 and 2006. MAIN OUTCOME MEASURES: Annual People Support and Capacity Building grants and expenditure, by broad research area, state or territory, administering institution, and Indigenous status (as self-identified by award recipients in their applications). RESULTS: Between 1996 and 2006, 134 People Support awards were made to researchers studying Indigenous health; of these, 27 (20%) were to researchers who self-identified as Aboriginal or Torres Strait Islander. In 2006, about 2.9% of the annual expenditure on all People Support funding was for Indigenous health research, representing a doubling in the proportion of funds since 2001. There was no increase in the number of self-identified Indigenous researchers funded under People Support, but Capacity Building Grants increased the number of people from Indigenous backgrounds supported by the NHMRC, with funds allocated to 36 Indigenous researchers from 2002 to 2006, compared with 14 funded by People Support during the same period. CONCLUSIONS: Funding to support Indigenous health research through the People Support scheme has increased since the NHMRC adopted policy changes in 2002, but it has not reached the targeted expenditure of at least 5% of agency allocations. The Capacity Building Grants have been a more effective vehicle for funding researchers from Indigenous backgrounds.

Research funding at colleges of osteopathic medicine: 15 years of growth.

CONTEXT: Colleges of osteopathic medicine (COMs) trying to stimulate research and develop research infrastructures must overcome the challenge of obtaining adequate funding to support growing research interests. The authors examine changes in research funding at COMs during the past 15 years. OBJECTIVES: To track 1999-2004 data on COM research funding, COM faculty size, educational backgrounds of principal investigators receiving funding, and funding institutions. To compare these data with published results from 1989 to 1999. METHODS: Data on number of grants, funding amounts by extramural source, percent of total dollars by extramural source, percent of total dollars by COM, and total amount of extramural funding were obtained from the American Association of Colleges of Osteopathic Medicine databases. Data on the Osteopathic Research Center (ORC) were obtained from the ORC's databases. RESULTS: Research, both in terms of number of grants and funding amounts within the osteopathic medical profession, increased substantially from 1999 to 2004. The largest single source of funding remained the National Institutes of Health. The number of COMs whose research funding exceeded $1 million annually more than doubled, increasing from 5 in 1999 to 12 in 2004. The osteopathic medical profession's decision to direct research dollars into a national research center devoted to research specific to osteopathic manipulative medicine resulted in an almost eightfold return on initial investment in 4 years. CONCLUSIONS: The amount of research productivity at a COM may be aligned with the size of the COM's full-time faculty, suggesting that once "critical mass" for teaching, service, and administration are achieved, a productive research program can be realized. Expanding the evidence base for those aspects of medicine unique to the osteopathic medical profession is dependent on the future growth of research.

Research priorities for urological care following spinal cord injury: recommendations of an expert panel.

OBJECTIVE: A multidisciplinary panel of experts from Canada and the United States was convened by the Ontario Neurotrauma Foundation (ONF) to establish research priorities in the area of urological care following spinal cord injury (SCI). DESIGN: The panel reviewed a synthesis of published literature in five areas of urology, identified emerging opportunities in the private and public sector, and used a modified Delphi approach to reach consensus on priorities for funding. RESULTS: The panel recommendations included: clinical trials of the safety and efficacy of M3 receptor specific anti-muscarinic agents for bladder hyperactivity in SCI patients; development and testing of protocols for sacral nerve electrostimulation without sacral afferent neurectomy for management of micturition - including selective stimulation of sacral nerve fibers, high frequency blocking of the pudendal nerve to minimize the risk of urethral sphincter co-contraction and genital nerve stimulation for bladder inhibition and incontinence management; clinical trials of the efficacy and safety of intra-urethral valve catheters; trials of the efficacy of probiotics for bacterial interference i.e. to reduce colonization by uropathogens and manage the dual problems of infection and pathogen resistance to anti-microbials: innovations in the prevention or treatment of stone disease (ureteral, bladder and kidney). CONCLUSIONS: The recommendations form the strategic priorities of the ONF SCI grants program for Ontario-based investigators and their partnerships with out-of-province collaborators and organizations.