Final Draft 11 Free Trial

[Browning Winters]

Inhigh-income countries, 6% of all women will have sustained a fracture of the wrist (distal radius) by the age of 80 years and 9% by the age of 90 years. Advances in orthopaedic surgery have improved the outcome for patients: many such fractures can be treated in a plaster cast alone, but others require surgical fixation to hold the bone in place while they heal. The existing evidence suggests that modern locking-plate fixation provides improved functional outcomes, but costs more than traditional wire fixation.

In this multicentre trial, we randomly assigned 461 adult patients having surgery for an acute dorsally displaced fracture of the distal radius to either percutaneous Kirschner-wire fixation or locking-plate fixation. The primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE) questionnaire at 12 months after the fracture. In this surgical trial, neither the patients nor the surgeons could be blind to the intervention. We also collected information on complications and combined costs and quality-adjusted life-years (QALYs) to assess cost-effectiveness.

Contrary to the existing literature, and against the increasing use of locking-plate fixation, this trial shows that there is no difference between Kirschner wires and volar locking plates for patients with dorsally displaced fractures of the distal radius. A Kirschner-wire fixation is less expensive and quicker to perform.

This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 17. See the NIHR Journals Library website for further project information.

Amar Rangan reports grants and personal fees from DePuy Ltd and grants from JRI Ltd; both are outside the submitted work. In addition, Professor Rangan has UK and European patent applications pending. Sarah Lamb is chairperson of the Health Technology Assessment Clinical Trials and Evaluation Board.

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The purposes of eligibility criteria for cancer clinical trials are to select the intended patient population and reduce potential risks to trial participants. However, eligibility criteria are sometimes more restrictive than necessary, and expanding eligibility criteria to be more inclusive is one trial design consideration that may improve the diversity of clinical trial populations. This guidance is one in a series of guidances that provide recommendations regarding eligibility criteria for clinical trials of investigational drugs regulated by CDER and CBER for the treatment of cancer. Specifically, this guidance includes recommendations for selecting appropriate laboratory values as trial eligibility criteria to avoid unjustified exclusions of diverse trial participants. This guidance intends to assist interested parties, including sponsors and/or institutional review boards, who are responsible for the development and oversight of clinical trials.

The National Institutes of Health (NIH) is seeking public comments on a draft policy to promote broad and responsible dissemination of information on clinical trials funded by the NIH through registration and submission of summary results information to ClinicalTrials.gov.

The NIH is dedicated to improving the health of Americans by conducting and funding biomedical and behavioral research, including clinical trials.1 A fundamental premise of all NIH-funded research is that the results of such work must be disseminated in order to contribute to the general body of scientific knowledge and, ultimately, to the public health. NIH awardees are expected to make the results and accomplishments of their activities available to the research community and to the public at large.

The results of NIH-funded research can be disclosed in a number of ways, including through publications, presentations at scientific meetings, sharing research tools, and depositing information into databases and materials into repositories. NIH has a number of policies that promote the dissemination of research results and guide funding recipients in disseminating their results. The NIH Data Sharing Policy, the NIH Public Access Policy, the NIH Research Tools Policy, and the NIH Genomic Data Sharing Policy are important examples of policies to ensure that research data and materials generated using NIH funds are used productively to further scientific progress and to promote public health.2 Increasing public access to information from NIH research supports the public access and data sharing directives of the Executive Office of the President (EOP Directives).3

Traditionally, scientists fulfill their obligation to contribute to the general body of knowledge through peer reviewed journal publications. However, journal publication is not always possible, and many clinical trials are not being published or published in a timely manner. A recent study found that the results of less than half of NIH-funded clinical trials had been published in a peer-reviewed biomedical journal within 30 months of trial completion.4 Selective publication of the results of some trials and not others or publication of incomplete or partial findings from a particular trial can lead to inappropriate conclusions about the usefulness of particular therapies.5

Some NIH-funded clinical trials are subject to mandatory registration and reporting of results under federal law, i.e., Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA). FDAAA applies, in general, to controlled, interventional studies of Food and Drug Administration (FDA)-regulated drugs, biological products, and devices, excluding phase 1 studies of drugs and biological products and small feasibility studies of devices. Under FDAAA, a minimal set of summary information about such clinical trials must be submitted in a structured, tabular format to ClinicalTrials.gov, a freely accessible and searchable registry and results data bank operated by the National Library of Medicine (NLM), NIH.

NIH is proposing to issue a policy to ensure that all NIH-funded clinical trials are registered and have summary results, including adverse event information, submitted to ClinicalTrials.gov. Compliance with this policy will be a term and condition in the Notice of Grant Award and a contract requirement in the Contract Award. This proposed policy supports the NIH mission to advance the translation of research results into knowledge, products, and procedures that improve human health.

NIH encourages the public to provide comments on any aspect of the draft policy, described below, by February 19, 2015. Comments should be submitted electronically to the Office of Clinical Research and Bioethics Policy, Office of Science Policy, NIH, via email at clinicaltrials.di...@mail.nih.gov, mail at 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892, or by fax at 301-496-9839.

The purpose of this Policy is to promote broad and responsible dissemination of information from NIH-funded clinical trials through ClinicalTrials.gov, the clinical trial registry and results databank operated by the National Library of Medicine (NLM). Disseminating this information supports the NIH mission to advance the translation of research results into knowledge, products, and procedures that improve human health. This Policy is intended to complement the statutory mandate under Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) that requires registration and submission of summary results for certain clinical trials, whether funded by NIH or by other entities, to ClincalTrials.gov.6

This Policy applies to all NIH-funded awardees and investigators conducting clinical trials, funded in whole or in part by NIH, regardless of study phase, type of intervention, or whether they are subject to the FDAAA registration and results submission requirements set forth in Section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)). For purposes of this Policy, a clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes7.

As set forth in the terms and conditions of grant and contract awards, all NIH-funded awardees and investigators conducting clinical trials, funded in whole or in part by NIH, who have committed to NIH that they will comply with NIH policies, are expected to ensure that their NIH-funded clinical trials are registered and summary results, including adverse event information, are submitted to ClinicalTrials.gov in accord with the timelines that will be set forth at ClinicalTrials.gov. Generally, this means registration of the clinical trial not later than 21 days after enrollment of the first participant and submission of summary results information not later than one year after the completion date. Completion date is defined to be the date that the final subject was examined or received an intervention for the purpose of final collection of data for the primary outcome, whether the clinical trial concluded according to the pre-specified protocol or was terminated. It will be possible to delay results submission for up to two years beyond the initial deadline with a certification that regulatory approval of the product is being sought. Clinical trials covered by the policy will be expected to submit the same type of registration and results data and in the same timeframes as the trials subject to FDAAA. The specific registration and results information to be submitted will be made available at the ClinicalTrials.gov site.

Institutions and investigators should submit information directly to ClinicalTrials.gov. If the trial is subject to FDAAA, i.e., section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)), submissions must be made by the Responsible Party, as defined at 42 U.S.C. 282(j)(1)(A)(ix). If an NIH-funded clinical trial is also subject to FDAAA, it needs to have only one entry in ClinicalTrials.gov that contains its registration and results information. Investigators and funding recipients are expected to cooperate with NLM to address any data curation or quality control issues to facilitate timely posting.

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