[News release] Posting of trials results to online public database lagging, say Duke researchers

“What’s published in medical journals doesn’t necessarily match what was reported in clinicaltrials.gov….In a significant proportion of cases, the results on cliniclaltrials.gov were reported more thoroughly than the results in corresponding journal articles,”

From the March 2015 Medicine News post from Duke University

Despite legal and ethical mandates for disclosure, results from most clinical trials of medical products are not reported promptly atclinicaltrials.gov, according to Duke Medicine researchers.

Among all clinical trials of medical products, those funded by industry were the most likely to be publicly disclosed in a timely fashion, but even then, compliance was poor.

Research funded by the National Institutes of Health and academic institutions lagged further, according to findings published by Monique Anderson, MD, assistant professor of medicine (Cardiology), and her DCRI colleagues in the March 12, 2015, issue of The New England Journal of Medicine.

• Read the findings: Compliance with Results Reporting at ClinicalTrials.gov.
  From the results section
  “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.”
• Read a blog post about the study at Rethinking Clinical Trials, the NIH Collaboratory’s Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical TrialsExcerpts
  ““We were really surprised at how untimely the reporting was—and that more than 66 percent hadn’t reported at all over the 5 years [of the study interval],””Another unexpected result was the finding that industry-sponsored studies were significantly more likely to have reported timely results than were trials sponsored by the National Institutes of Health (NIH) or by other academic or government funding sources. The authors noted that despite a seemingly widespread lack of compliance with both legal and ethical imperatives for reporting trial results, there has so far been no penalty for failing to meet reporting obligations,””reporting clinical trials results in order to contribute to scientific and medical knowledge is as much an ethical obligation for researchers as a legal one: “It’s something we really promise to every patient when they enroll on a trial.””
• Listen to a report, with quotes from Dr. Anderson and Mark Stacy, MD, vice dean for clinical research, on National Public Radio: Results Of Many Clinical Trials Not Being ReportedExcerpts
  “Even counting the late entries and allowable exceptions, only about 50 percent of taxpayer-funded research has been reported back to the taxpayers on clinicaltrials.gov, ”
  “The study doesn’t assess why universities are frequently failing to post their results.”
  “scientists are generally more likely to publish good news and ignore bad news, which skews the scientific record.”
  “What’s published in medical journals doesn’t necessarily match whatwas reported in clinicaltrials.gov.”In a significant proportion of cases, the results on cliniclaltrials.gov were reported more thoroughly than the results in corresponding journal articles,” he says.
• Visit clinicaltrials.gov

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HHS and NIH take steps to enhance transparency of clinical trial results

From the HHS Press Release,  Wednesday, November. 19, 2014

 The U.S. Department of Health and Human Services today issued a Notice of Proposed Rulemaking (NPRM), which proposes regulations to implement reporting requirements for clinical trials that are subject to Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA). The proposed rule clarifies requirements to clinical researchers for registering clinical trials and submitting summary trial results information to ClinicalTrials.gov, a publicly accessible database operated by the National Library of Medicine, part of the National Institutes of Health. A major proposed change from current requirements is the expansion of the scope of clinical trials required to submit summary results to include trials of unapproved, unlicensed, and uncleared products.

…

….

ClinicalTrials.gov currently contains registration information for more than 178,000 clinical trials and summary results for more than 15,000. These numbers include trials that are not subject to FDAAA. Among the primary benefits of registering and reporting results of clinical trials, including both positive and negative findings, is that it helps researchers prevent unnecessary duplication of trials, particularly when trial results indicate that a product under study may be unsafe or ineffective, and it establishes trust with clinical trial participants that the information from their participation is being put to maximum use to further knowledge about their condition.

Developed by NIH in close coordination with the FDA, the proposed rule details procedures for meeting the requirements established by FDAAA to improve public access to clinical trial information. FDAAA and the proposed rule apply to certain interventional studies of drugs, biological products, and devices that are regulated by the FDA, but, generally, not to phase 1 trials of drugs and biological products and small feasibility studies of devices. The proposed rule specifies how data collected and analyzed in a clinical trial would be required to be submitted to ClinicalTrials.gov. It would not affect requirements for the design or conduct of clinical trials or for the data that must be collected during clinical trials.

“This proposed rule would close an important gap, making additional information about clinical studies of investigational drugs, medical devices and biological products available to the public,” said FDA Commissioner Margaret A. Hamburg, M.D. “It would help eliminate unnecessary duplicative trials, advance biomedical innovation, and provide the public with a much richer understanding about the clinical trials for these products.”

Notable changes from current requirements and practice that are outlined in the proposed rule include:

A streamlined approach for determining which trials are subject to the proposed regulations and who is responsible for submitting required information.

Expansion of the set of trials subject to summary results reporting to include trials of unapproved products.

Additional data elements that must be provided at the time of registration (not later than 21 days after enrolling the first participant) and results submission (generally not later than 12 months after completion).

Clarified procedures for delaying results submission when studying an unapproved, unlicensed, or uncleared product or a new use of a previously approved, licensed, or cleared product and for requesting extensions to the results submission deadline for good cause.

More rapid updating of several data elements to help ensure that users of ClinicalTrials.gov have access to accurate, up-to-date information about important aspects of a clinical trial.

Procedures for timely corrections to any errors discovered by the responsible party or by the Agency as it processes submissions prior to posting.

 

 

Read a summary of the proposed changes: http://www.nih.gov/news/health/nov2014/od-19_summary.htm.

Read the entire text of the proposed regulations here. Options are available for comment submission electronically or in written form.

 

Unpublished trial data ‘violates an ethical obligation’ to study participants, say researchers

Flowchart of four phases (enrollment, intervention allocation, follow-up, and data analysis) of a parallel randomized trial of two groups, modified from the CONSORT 2010 Statement Schulz KF, Altman DG, Moher D; for the CONSORT Group (2010). “CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials”. BMJ 340 : c332. doi:10.1136/bmj.c332. PMC 2844940. PMID 20332509 . . (Photo credit: Wikipedia)

 

From the 29 October 2013 British Medical Journal press release

 

Study finds almost 1 in 3 large clinical trials still not published 5 years after completion

Almost one in three (29%) large clinical trials remain unpublished five years after completion. And of these, 78% have no results publicly available, finds a study published on bmj.com today.

This means that an estimated 250,000 people have been exposed to the risks of trial participation without the societal benefits that accompany the dissemination of their results, say the authors.

They argue that this “violates an ethical obligation that investigators have towards study participants” and call for additional safeguards “to ensure timely public dissemination of trial data.”

Randomized clinical trials are a critical means of advancing medical knowledge. They depend on the willingness of people to expose themselves to risks, but the ethical justification for these risks is that society will eventually benefit from the knowledge gained from the trial.

But when trial data remain unpublished, the societal benefit that may have motivated someone to enrol in a study remains unrealized.

US law requires that many trials involving human participants be registered – and their results posted – on the largest clinical trial website ClinicalTrials.gov. But evidence suggests that this legislation has been largely ignored.

So a team of US-based researchers set out to estimate the frequency of non-publication of trial results and, among unpublished studies, the frequency with which results are unavailable in theClinicalTrials.gov database.

They searched scientific literature databases and identified 585 trials with at least 500 participants that were registered with ClinicalTrials.gov and completed prior to January 2009. The average time between study completion and the final literature search (November 2012) was 60 months for unpublished trials.

Registry entries for unpublished trials were then reviewed to determine whether results for these studies were available in the ClinicalTrials.gov results database.

Of 585 registered trials, 171 (29%) remained unpublished. Of these, 133 (78%) had no results available in ClinicalTrials.gov. Non-publication was more common among trials that received industry funding (32%) than those that did not (18%).

“Our results add to existing work by showing that non-publication is an important problem even among large randomized trials,” say the authors. Furthermore, the sponsors and investigators of these unpublished trials infrequently utilize the ClinicalTrials.gov results database.

The lack of availability of results from these trials “contributes to publication bias and also constitutes a failure to honor the ethical contract that is the basis for exposing study participants to the risks inherent in trial participation,” they add. “Additional safeguards are needed to ensure timely public dissemination of trial data,” they conclude.

 

 

 

 

 

Related articles

• Non-publication of large randomized clinical trials: cross sectional analysis (medicalnewstoday.com)
• ‘Ethical failure’ leaves one-quarter of all clinical trials unpublished (blogs.nature.com)
• A third of clinical trials haven’t published results (alltrials.net)
• Scientists voice fears over ethics of drug trials remaining unpublished (theguardian.com)
• The State of Infectious Diseases Clinical Trials: A Systematic Review of ClinicalTrials.gov (plosone.org)
• Scientists alarmed over ethics of drug trials remaining unpublished up to five years after they’re finished (rawstory.com)

 

New Style and New Content for ClinicalTrials.gov

From the US National Library of Medicine August 2012 press release

ClinicalTrials.gov is the NLM-developed Web-based registry and results database of clinical research studies. The Web site provides patients, clinicians, researchers, and the public with access to information about interventional and observational studies. As of August 2012, ClinicalTrials.gov contained over 130,000 clinical research studies in all fifty states and in 179 countries.

On August 13, 2012, visitors to the ClinicalTrials.gov Web site and the accompanying Protocol Registration System (PRS) Information Web site (designed for data providers) saw a link to a beta site including a new integrated homepage and updated graphic design for the site (http://clinicaltrials.gov/beta/).

Visitors will also have access to new and reorganized written content about clinical research, background information about the site, searching for studies, and maintaining study records.

However, core functions of the site — including the basic and advanced search, search results options, and the study record data – will remain the same. The new site interface will run in parallel with the previous version for approximately four weeks after launch. After appropriate testing and additional minor changes it will permanently replace the previous interface.

The New Homepage

The homepage (see Figure 1) showcases the study search options and search help resources in one location, the “Search for Studies” area. Site visitors can begin a basic search here, go to the advanced search form, or begin browsing for studies by topic or on a world map. Site visitors can also get help with searching, finding studies with summary results posted on ClinicalTrials.gov, and reading study records.

A new menu bar provides direct access to each area of content on the site (See Navigating the Site). Custom views of this content have been created for different user groups. Patients and families, researchers, and study record managers are three significant groups that visit ClinicalTrials.gov. The homepage areas for these audiences provide an introduction to content for each user group, and the “Learn more” link in each area goes to an orientation page that highlights relevant resources on the site. For example, study record managers can find out which clinical trials should be registered with ClinicalTrials.gov and get help with setting up accounts, registering studies and updating records. Members of the press also have a new page with background information and statistics about the site (see the “Media/Press Resources” page under “About Us” in the menu bar).

Data about the site are highlighted in the right column of the homepage. Users can access “Trends, charts, and maps” content for more statistics. An enhanced Glossary provides descriptions of clinical research terms commonly used on ClinicalTrials.gov and “Using our RSS Feeds” explains how to get notification of new and updated study records.

Figure 1: New ClinicalTrials.gov homepage.

 

Please click here for more figures on how to

• How to search for clinical trials
• How to find information on study records (clinical trial sites and study organizers)
• How to find selected outreach and scholarly publications related to ClinicalTrials.gov and clinical research

Related articles

• New Look and Content for ClinicalTrials.gov (hslnews.wordpress.com)
• Clinical trials often fall short: US study (news.com.au)
• Global Clinical Trials: Preferred CRO Partnerships, 1-2 October 2012, Philadelphia, PA (medicalnewstoday.com)

Researchers lead search for better drug-addiction treatments

Researchers lead search for better drug-addiction treatments

From a February 2, 2011 Eureka news alert

DALLAS – Feb. 3, 2011 – UT Southwestern Medical Center psychiatry researchers(Division of Addictions)are leading the Texas arm of a national network that conducts clinical trials aimed at finding effective treatments for drug addiction.

More than 100 community treatment providers and academic medical centers throughout the country are funded in part through the National Institute on Drug Abuse’s Clinical Trials Network (CTN). The Texas component includes partnerships between academic and community treatment providers in Dallas, El Paso, Austin and Houston. It is led by Dr. Madhukar Trivedi, professor of psychiatry at UT Southwestern.

“The effects of drugs on the brain are very clear, but we still need long-term answers that cure people who abuse drugs and prevent them from relapse,” Dr. Trivedi said. “I applaud NIDA for funding the infrastructure at academic institutions to research therapies in real-world treatment centers that will lead to ready-to-launch cures. Drug abuse affects not just the person, but families and society as a whole.”

Each CTN study is conducted in multiple community treatment provider sites across the country, led by a CTN substance abuse researcher and supported by the researchers in the CTN academic institutions affiliated with each participating site.

“It is critical to find new treatments in the substance abuse field where current treatments result in only modest improvements. Finding effective interventions really requires larger, multicenter treatment trials like those occurring in the CTN,” Dr. Trivedi said.

One such national study within the CTN is the Stimulant Reduction Intervention Using Dose Exercise (STRIDE)**, led by Dr. Trivedi. It is a groundbreaking study that tests the short and longer term effectiveness of adding either exercise or health education to treatment as usual in adults who abuse stimulants such as cocaine or methamphetamine. Sites participating in this study in Texas include Nexus Recovery Center and Memorial Hermann Prevention and Recovery Center as well as multiple other sites across the country.

Other studies being conducted in the CTN in Texas include a trial that tests whether an interactive web-based therapy added to usual treatment improves abstinence from drug use, and a trial that examines whether medication, counseling, and incentives to quit smoking added to usual treatment improve abstinence from drug use.

Dr. Trivedi recently received a renewal of the National Institute on Drug Abuse‘s grant to continue contributions to improve the treatment of addiction for several additional years and said he expects to receive nearly $4 million over the next year.

A national CTN goal for the next few years is to engage other types of medical doctors and treatment settings who treat people addicted to drugs, in research, including primary care, internal medicine and emergency-room physicians. “We will be expanding our reach,” Dr. Trivedi said.

 

**ClinicalTrials.gov has information about federally and privately supported clinical trials, as quoted  news release item above.

Some clinical trials studies post their results at ClinicalTrials.gov.
Check the About page and Understanding Clinical Trials at Clinical Trials.gov for more information.

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