A free source of evidence-based information for health care professionals and for researchers studying liver injury associated with prescription and over-the-counter drugs, herbals, and dietary supplements is now available from the National Institutes of Health. Researchers and health care professionals can use the LiverTox database to identify basic and clinical research questions to be answered and to chart optimal ways to diagnose and control drug-induced liver injury.
Drug-induced liver injury is the leading cause of acute liver failure in the United States, accounting for at least half of cases. It occurs at all ages, in men and women, and in all races and ethnic groups. Drug-induced liver disease is more likely to occur among older adults because they tend to take more medications than younger people. Some drugs directly damage the liver, while others cause damage indirectly or by an allergic reaction. The most important element to managing drug-induced liver injury is to identify the drug that’s causing the problem and appropriate steps to eliminate or reduce damage to the liver.
“Because drug-induced liver disease is not a single, common disease, it is very difficult to diagnose, with each drug causing a somewhat different pattern of liver damage,” said Jay H. Hoofnagle, M.D., the major creator of LiverTox and director of the Liver Disease Research Branch at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “Doctors have to rule out all other causes of liver disease before saying that a patient has drug-induced injury liver.”
LiverTox has a searchable database of about 700 medications available in the United States by prescription or over the counter. Over the next few years, another 300 drugs will be added. The database offers these features:
- An overview of drug-induced liver injury, including diagnostic criteria, the role of liver biopsy, descriptions of different clinical patterns and standard definitions.
- A detailed report of each drug, including background, case study, product package insert, chemical makeup and structure, dose recommendations and references with links.
- An interactive section, allowing users to report cases of drug-induced liver injury to the LiverTox website. Reports will be automatically forwarded to the Food and Drug Administration’s (FDA) MedWatch program. MedWatch allows the public and health care professionals to report adverse events, product defects, or product use errors. The FDA uses the information to monitor product safety.
“LiverTox is the result of a significant scientific collaboration between the national and international clinical and research communities, the NIDDK and the National Library of Medicine (NLM),” said Steven Phillips, M.D., co-sponsor of LiverTox and director of NLM’s Division of Specialized Information Services. “LiverTox demonstrates the importance of using informatics to provide easy access to evidenced-based information to clinicians and researchers that will improve the health and well-being of all and help prevent unnecessary morbidity and mortality, worldwide. I hope the dynamic LiverTox model can be used to create a new suite of databases that can identify drug-induced injury to other organs such as the heart, kidney, and lung. The National Library of Medicine is honored to be part of this significant scientific endeavor.”
- NIH launches LiverTox a free database of drugs linked to liver injury (hslnews.wordpress.com)
- NIH launches free database of drugs associated with liver injury (medicalxpress.com)
- Drug Induced Liver Dysfunction Lab Values (jessicamhpower.wordpress.com)
Many NIH-funded clinical trials go unpublished over two years after completion (with ClinicalTrials.gov link for many trial study results)
[Flahiff's note: It is possible that many of these unpublished clinical trial results would have made a positive difference in many people's lives. These unpublished results have the potential of aiding many researchers. They can prevent unnecessary duplicate trials, point to areas needing more research, and potentially provide groundwork for collaboration.
On another note, it is good to see that published research papers are now more accessible to all. As of 2008, research papers based on NIH grants must be submitted to PubMed Central (PMC) when those papers are accepted for publication in a peer-reviewed journal. PMC will then make the papers freely available to the public within 12 months of publication.
I look forward to the day when all research papers are freely available to the public. There are a myriad of issues, as who pays for the publishing, the peer review process, and where the research papers should be "housed". However, I believe the more scientific research results are disseminated in easily accessible format, the more we can advance in technology applications and filling in knowledge gaps.]
In a study that investigates the challenges of disseminating clinical research findings in peer-reviewed biomedical journals, Yale School of Medicine researchers have found that fewer than half of a sample of trials primarily or partially funded by the National Institutes of Health (NIH) were published within 30 months of completing the clinical trial.
These findings appear in the January issue of the British Medical Journal, which focuses on the topic of unpublished evidence.
“When research findings are not disseminated, the scientific process is disrupted and leads to redundant efforts and misconceptions about clinical evidence,” said Dr. Joseph Ross, first author of the study and a Yale assistant professor of medicine. “Such inaction undermines both the trial in question and the evidence available in peer-reviewed medical literature. This has far-reaching implications for policy decisions, and even institutional review board assessments of risks and benefits associated with future research studies.”…
Ross said that there may be many reasons for lack of publication, such as not getting accepted by a journal or not prioritizing the dissemination of research findings. Still, he said, there are alternative methods for providing timely public access to study results, including the results database at ClinicalTrials.gov** that was created in response to Federal law.
[From the About Page at Clinical Trials.gov
US Public Law 110-85 (Food and Drug Administration Amendments Act of 2007 or FDAAA), Title VIII, Section 801 mandates that a "responsible party" (i.e., the study sponsor or designated principal investigator) register and report results of certain "applicable clinical trials" that were initiated or ongoing as of September 27, 2007...]
ClinicalTrials.gov offers up-to-date information for locating federally and privately supported clinical trials for a wide range of diseases and conditions.
ClinicalTrials.gov currently contains 118,682 trials sponsored by the National Institutes of Health, other federal agencies, and private industry.
**Here is how one can check for study results
(remember, researchers are not mandated to submit study results to ClinicalTrials.gov, they are voluntary)
ClinicalTrials.gov records with published results listed via the PubMed medical literature search service.
- Use the Advanced Search with the search phrase clinicaltrials.gov[si]
Use the Builder limit results by topics (as a disease, medical device), year(s), name of researcher/invesitator)
- Need help searching? PubMed has tutorials , including a YouTube at the Advanced Search Page
Ask for assistance from a reference librarian at your local public, academic, hospital, or medical library.
Many academic, hospital, and medical libraries offer at least basic search help to all. Call ahead and ask
about their services. You may be pleasantly surprised.
- Many NIH-funded clinical trials go unpublished over 2 years after completion (eurekalert.org)
- The White House Calls for Information on Public Access to Publications and Data (The Scholarly Kitchen)
- How to obtain free/low cost medical and scientific articles(jflahiff.wordpress.com)
- Patients want to understand the medical literature (with links to resources for patients) (jflahiff.wordpress.com)
- Missing trial data threatens the integrity of medicine (eurekalert.org)
- Poor patient recruitment cited in call for trial disclosures (fiercebiotechit.com)
- A Present for NIH: President Signs Law Creating New Translational Center (news.sciencemag.org)
- NIH and Non-profits Sign Research and Development Agreement (kauffman.org)
- NIH establishes National Center for Advancing Translational Sciences (jflahiff.wordpress.com)
In a move to re-engineer the process of translating scientific discoveries into new drugs, diagnostics, and devices, the National Institutes of Health has established the National Center for Advancing Translational Sciences (NCATS). The action was made possible by Congress’ approval of a fiscal year 2012 spending bill and the president’s signing of the bill, which includes the establishment of NCATS with a budget of $575 million.
NCATS will serve as the nation’s hub for catalyzing innovations in translational science. Working closely with partners in the regulatory, academic, nonprofit, and private sectors, NCATS will strive to identify and overcome hurdles that slow the development of effective treatments and cures.
“Congressional support for the National Center for Advancing Translational Sciences marks a major milestone in mobilizing the community effort required to revolutionize the science of translation,” said NIH Director Dr. Francis S. Collins, M.D., Ph.D. “Patients suffering from debilitating and life threatening diseases do not have the luxury to wait the 13 years it currently takes to translate new scientific discoveries into treatments that could save or improve the quality of their lives. The entire community must work together to forge a new paradigm, and NCATS aims to catalyze this effort.”
A prime example of the type of innovative projects that will be led by NCATS is the new initiative between NIH, the Defense Advanced Research Projects Agency, and the U.S. Food and Drug Administration to develop cutting-edge chip technology. This new technology will allow researchers to screen for safe and effective drugs far more swiftly and efficiently than current methods. A great deal of time and money can be saved testing drug safety and effectiveness much earlier in the process.
To meet the goals of NCATS, NIH is reorganizing a wide range of preclinical and clinical translational science capabilities within NIH into an integrated scientific enterprise with new leadership and a bold new agenda. While the effort to recruit an NCATS director continues, organizational changes and realignment of resources will move forward under the leadership of Acting Director Thomas R. Insel, M.D., and Acting Deputy Director Kathy Hudson, Ph.D. Dr. Insel is the director of the National Institutes of Mental Health and Dr. Hudson is the deputy director for science, outreach, and policy at the National Institutes of Health.
The following programs will comprise NCATS:
- Bridging Interventional Development Gaps, which makes available critical resources needed for the development of new therapeutic agents
- Clinical and Translational Science Awards, which fund a national consortium of medical research institutions working together to improve the way clinical and translational research is conducted nationwide
- Cures Acceleration Network, which enables NCATS to fund research in new and innovative ways
- FDA-NIH Regulatory Science, which is an interagency partnership that aims to accelerate the development and use of better tools, standards and approaches for developing and evaluating diagnostic and therapeutic products
- Office of Rare Diseases Research, which coordinates and supports rare diseases research
- Components of the Molecular Libraries, which is an initiative that provides researchers with access to the large-scale screening capacity necessary to identify compounds that can be used as chemical probes to validate new therapeutic targets
- Therapeutics for Rare and Neglected Diseases, which is a program to encourage and speed the development of new drugs for rare and neglected diseases
The budget for NCATS is primarily a reallocation of funds from programs previously located in the NIH Office of the Director, National Human Genome Research Institute, and National Center for Research Resources. NIH is committed to both basic and applied research and has maintained a relatively stable ratio of funding across these two areas of focus. The funding ratio will not be disturbed by the establishment of this new center.
The formation of NCATS has been a methodical process highlighted by the recommendation of the NIH Scientific Management Review Board in December 2010 to create a new center dedicated to advancing translational science. This recommendation was followed by a year of intensive feedback and expert insight from all sectors of translational science through advisory meetings and extensive public consultation.
“I am deeply grateful for the expertise and insight provided by the many researchers, industry executives, patients, voluntary organizations, and NIH staff that helped NIH evaluate NCATS’ purpose and crystallize its vision,” said Dr. Collins.
To learn more about the impetus and development of NCATS, go to:
- NCATS web page: http://www.nih.gov/about/director/ncats/index.htm.
- NCATS on the Feedback NIH website: http://feedback.nih.gov/index.php/category/ncats/
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visitwww.nih.gov.
- NIH Director Jumps the Gun With Memo Announcing New Center (news.sciencemag.org)
- NIH Chided on Translational Center, Warned of More Budget Cuts (news.sciencemag.org)
- NIH centre faces spell in limbo (nature.com)
- White House Boosts Translational Medicine, Drug Chip Project (news.sciencemag.org)
- US biomedical and energy budgets inch toward resolution (blogs.nature.com)
- Senate Panel Trims NIH Budget By $190 Million (news.sciencemag.org)
- New drug-discovery center lost in translation (fiercebiotechresearch.com)
- NIH launches $140M drug tox project, hunts for translational R&D chief (fiercebiotechresearch.com)
- Departing Director Reflects on NCRR Breakup (news.sciencemag.org)
- IEA Places 18 Employees within the National Institutes of Health (NIH) (prnewswire.com)
[On a somewhat related note...
About three years ago I created an Online Library Guide entitled Animal Research Alternatives to aid researchers at the university where I worked as a reference librarian. Specifically it aimed to "To support research scientists in searching the literature in order to comply with the Animal Welfare Act (7USC 2131-2156)"
The process of creating the guide was challenging, but very enjoyable.]
From the 18 December 2011 article at AllGov by Noel Brinkerhoff
A panel of experts commissioned by the National Institutes of Health (NIH) has concluded that most of the research involving chimpanzees is not necessary. According to the most recent count, there are 937 chimpanzees being used for research in the United States, including 612 for projects funded by the U.S. government. They are most commonly used for hepatitis-related research.On December 15, the NIH suspended new grants for research that uses chimps.The NIH asked researchers to examine the many ways chimps are utilized in medical and social experiments to determine the value of this work. The panel decided that “while the chimpanzee has been a valuable animal model in past research, most current use of chimpanzees for biomedical research is unnecessary.”However, the study stopped short of recommending that chimps never be used by scientists.They said there is rationale for using the primates in research on: monoclonal antibody therapies; comparative genomics; and non-invasive studies of social and behavioral factors that affect the development, prevention, or treatment of disease.Guidelines also were offered for justifying the use of chimps, these being:· That the knowledge gained must be necessary to advance the public’s health;· There must be no other research model by which the knowledge could be obtained, and the research cannot be ethically performed on human subjects; andThe animals used in the proposed research must be maintained either in ethologically appropriate physical and social environments (i.e., as would occur in their natural environment) or in natural habitats.In April, Sen. Maria Cantwell (D-Washington) introduced the Great Ape Protection and Cost Savings Act of 2011, which would prohibit invasive research on chimpanzees.
- Most Biomedical Research Chimps Can Retire, Panel Finds (organicauthority.com)
- Fewer animal experiments thanks to nanosensors (Eureka alert)
- NIH to Limit Use of Chimps in Research (artofthestem.com)
- Experiments With Chimps (andrewsullivan.thedailybeast.com)
- U.S. report recommends stringent limits on use of chimpanzees in biomedical, behavioural research (thehindu.com)
- Chimpanzee Research on Way Out (bigthink.com)
- Research Chimpanzees Offered Hope (theage.com.au)
- First Guidelines for Lab Chimps Drawn Up (livescience.com)
- NIH Curtails Chimpanzee Research in Wake of IOM Report (news.sciencemag.org)
- Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity (bespacific.com)
A new research program funded by the National Institutes of Health will explore the role that a changing climate has on human health. Led by NIH’s National Institute of Environmental Health Sciences (NIEHS), the program will research the risk factors that make people more vulnerable to heat exposure; changing weather patterns; changes in environmental exposures, such as air pollution and toxic chemicals; and the negative effects of climate change adaptation and mitigation efforts.
In addition to better understanding the direct and indirect human health risks in the United States and globally, one of the program’s goals is to determine which populations will be more susceptible and vulnerable to diseases exacerbated by climate change. Children, pregnant women, the elderly, people from low socioeconomic backgrounds, and those living in urban or coastal areas and storm centers may be at elevated risk. This program will also help to develop data, methods, and models to support health impact predictions.
“Governments and policy makers need to know what the health effects from climate change are and who is most at risk,” said John Balbus, M.D., NIEHS senior advisor for public health and lead for NIEHS’ efforts on climate change. “The research from this program will help guide public health interventions, to ultimately prevent harm to the most vulnerable people.”
The funding program is an outgrowth of two previous efforts led by NIH. A December 2009 workshop, sponsored by a trans-NIH working group, brought leaders in the field together to begin identifying priorities for NIH climate change research. NIH then led the ad hoc Interagency Working Group on Climate Change and Health in developing an outline of research needs, which are described in a report available atwww.niehs.nih.gov/climatereport.
Summaries of supported public health initiatives may be found at Public Health Impacts.
“Discoveries by NIEHS-funded scientists have led to the development of prevention strategies, health and safety guidelines, and potential treatments for asthma, cardiovascular disease, cancer, and other environmentally-related diseases..”
This research has yielded numerous studies on indoor pollution and respiratory health, and led to the development of air sampling techniques used in research settings worldwide.
- Children’s Environmental Health
Research on the annual costs of environmentally-related diseases in American children will be useful in developing new strategies and guidelines for the detection and prevention of childhood illnesses.
- Pesticides & Neurodevelopment
The discovery of an enzyme that provides protection against the toxicity of pesticide compounds has led to the development of new treatments for nerve agent exposures.
NCI announces plans to reinvigorate clinical trials
Consolidation of cooperative group program is designed to bring enhanced efficiencies to oncological sciences
The National Cancer Institute (NCI) has announced major changes to be made in the long-established Clinical Trials Cooperative Group Program that conducts many of the nationwide trials of new cancer therapies. In a major transformation, NCI intends to consolidate the nine groups that currently conduct trials in adult cancer patients into four state-of-the-art entities that will design and perform improved trials of cancer therapies. These changes are designed to provide greater benefits for cancer patients and more information for researchers. These moves come in response to an NCI-requested April 2010 report from the Institute of Medicine (IOM)**, which called for a series of changes to the cooperative groups program, including restructuring….
….The April IOM report noted that the current trials system is inefficient, cumbersome, underfunded, and overly complex. The report recommended consolidating existing adult cooperative groups into a smaller number of groups that could function in a more closely integrated manner….
…For the past several decades, clinical cancer trials have used one or a combination of drugs or other treatment modalities, such as surgery or radiation, in comparison to the prevailing standard of care to see if the new treatment was superior. Recently, some trials have begun to depend on the genetic profiling of tumors. For example, one ongoing NCI-sponsored breast cancer study, called TAILORx, is examining whether genes that are frequently associated with risk of recurrence for women with early-stage breast cancer can be used to assign patients to more appropriate and effective treatments.
These types of studies necessitate the screening of large numbers of patients in order to find subsets of patients with tumors that demonstrate changes in specific genetic pathways. These trials therefore require acquisition and distribution of many tumor specimens, DNA sequencing, and the matching of genetic information with treatment options. The increased complexity of these trials provides a rationale for modernization and simplification of the current cooperative group structure…..
..On Jan. 1, 2011, NCI will impose new deadlines, formulated by its Operational Efficiency Working Group, which will reduce by half the time to initiate new clinical studies and will terminate studies not begun within two years of concept approval….
**The IOM Web site has over 50 results with the search phrase clinical trials, including the most viewed Biomedical/Health Research report (as of Dec 27, 2010) - Transforming Clinical Research in the US: Workshop Summary
General Information about Clinical Trials (select Web sites)
- Clinical Trials (MedlinePlus) has overviews, related issues (as informed consent and ethics), directories, and more
- Understanding Clinical Trials (ClinicalTrials.gov) answers many basic questions relating to participation, safety, ethics, and types of clinical trials
- ClinicalTrials.gov is a registry and finding aid for clinical trials. It currently has 100,613 trials with locations in 174 countries. One can search by topic (as a particular drug or disease) or use the advanced search to use limiters as location, conditions, age groups, and sponsors. Results give contact information for individual clinical trials.The page How can I find the results of a clinical trial? provides places where they might be found, including the ClinicalTrials.gov Web site.
Herbs at a glance: a quick guide to herbal supplements is a 100 page indexed PDF document which gives the basics on the most common herbs in dietary supplements – historical uses, what they are used for now, scientific evidence on effectiveness, and potential side effects.
It is published by the US National Center for Complementary and Alternative Medicine (NCAAM).
The NCAAM Web site includes links to information under titles as
- Health Topics A-Z with Evidence-based information on treatments and conditions
- Information for Consumers with numerous fact sheets to help you decide if complementary/alternative medicine is right for you. (Don’t forget to consult with your health care providers! These fact sheets can be great discussion starters)
- A good introductory page on What is Complementary and Alternative Medicine?
- News and Events
- Ways to get updates bv email, newsfeed (RSS), Twitter, Facebook, and Youtube
A few related Web sites
- Complementary and Alternative Medicine (MedlinePlus)has links to overviews, specific conditions, tutorials, videos, research, and more
- Herbal Medicine (MedlinePlus) has links to overviews, specific conditions, research, and more
- Complementary Medicine (NetWellness) has links to general information,treatment, and Ask-An-Expert answered questions. One can ask a question at this site, and receive a reply within a few days.
- Alternative Medicine (NIH) contains links to information at US government sites
- Drug Information Portal (NIH) provides a wealth of information for consumers and professionals.
- US Office of Dietary Supplements contains fact sheets, news items, decision making guidance, consumer protection information, nutrient recommendations, and more
and a related news item…
From the December 16, 2010 Health Day news item U.S. Spending Millions to See if Herbs Truly Work
THURSDAY, Dec. 16 (HealthDay News) — People have been using herbal supplements for centuries to cure all manner of ills and improve their health. But for all the folk wisdom promoting the use of such plants as St. John’s wort and black cohosh, much about their effect on human health remains unknown.
But the federal government is spending millions of dollars to support research dedicated to separating the wheat from the chaff when it comes to herbal supplements.
“A lot of these products are widely used by the consumer, and we don’t have evidence one way or the other whether they are safe and effective,” said Marguerite Klein, director of the Botanical Research Centers Program at the U.S. National Institutes of Health. “We have a long way to go. It’s a big job.”
In August, the U.S. National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements awarded about $37 million in grants to five interdisciplinary and collaborative dietary supplement centers across the nation. The grants were part of a decade-long initiative that so far has awarded more than $250 million toward research to look into the safety and efficacy of health products made from the stems, seeds, leaves, bark and flowers of plants.
Reliance on botanical supplements faded in the mid-20th century as doctors began to rely more and more on scientifically tested pharmaceutical drugs to treat their patients, said William Obermeyer, vice president of research for ConsumerLab.com, which tests supplement brands for quality.
But today, herbal remedies and supplements are coming back in a big way. People in the United States spent more than $5 billion on herbal and botanical dietary supplements in 2009, up 22 percent from a decade before, according to the American Botanical Council, a nonprofit research and education organization.
The increase has prompted some concern from doctors and health researchers. There are worries regarding the purity and consistency of supplements, which are not regulated as strictly as pharmaceutical drugs.
“One out of four of the dietary supplements we’ve quality-tested over the last 11 years failed,” Obermeyer said. The failure rate increases to 55 percent, he said, when considering botanical products alone.
Some products contain less than the promoted amount of the supplement in question — such as a 400-milligram capsule of echinacea containing just 250 milligrams of the herb. Other products are tainted by pesticides or heavy metals.
The U.S. Food and Drug Administration warned supplement makers on Dec. 15 that any company marketing tainted products could face criminal prosecution. The agency was specifically targeting products to promote weight loss, enhance sexual prowess or aid in body building, which it said were “masquerading as dietary supplements” and in some cases were laced with the same active ingredients as approved drugs or were close copies of those drugs or contained synthetic synthetic steroids that don’t qualify as dietary ingredients.
But even when someone takes a valid herbal supplement, it may not be as effective when taken as a pill or capsule rather than used in the manner of a folk remedy. For example, an herb normally ground into paste as part of a ceremony might lose its effectiveness if prepared using modern manufacturing methods, Obermeyer said.
“You move away from the traditional use out of convenience, and you may not have the same effect,” he said.
Researchers also are concerned that there just isn’t a lot of evidence to support the health benefits said to be gained from herbal supplements. People may be misusing them, which can lead to poor health and potential interactions with prescription drugs.
“Consumers often are taking them without telling their doctor, or taking them in lieu of going to the doctor,” Klein said……