NIH analysis shows Americans are in pain

Report examines the prevalence, severity, and duration of pain

A new analysis of data from the 2012 National Health Interview Survey (NHIS) has found that most American adults have experienced some level of pain, from brief to more lasting pain, and from relatively minor to more severe pain. The analysis helps to unravel the complexities of a Nation in pain. It found that an estimated 25.3 million adults (11.2 percent) had pain every day for the preceding 3 months. Nearly 40 million adults (17.6 percent) experience severe levels of pain. Those with severe pain are also likely to have worse health status. The analysis was funded by the National Institutes of Health’s National Center for Complementary and Integrative Health (NCCIH) and was published in The Journal of Pain.

Pain in the United States

“The number of people who suffer from severe and lasting pain is striking,” said Josephine P. Briggs, M.D., director of NCCIH. “This analysis adds valuable new scope to our understanding of pain and could inform the National Pain Strategy in the areas of population research and disparities. It may help shape future research, development, and targeting of effective pain interventions, including complementary health approaches.”

Pain is one of the leading reasons Americans turn to complementary health approaches such as yoga, massage, and meditation—which may help manage pain and other symptoms that are not consistently addressed by prescription drugs and other conventional treatments. For this reason, NCCIH research priorities include the study of complementary approaches to determine their effectiveness for treating symptoms such as pain.

The CDC’s NHIS is an annual study in which tens of thousands of Americans are interviewed about their health- and illness-related experiences. The 2012 NHIS asked participants about the frequency and intensity of pain experienced in the prior 3 months. The survey results are based on combined data from 8,781 American adults from a subsection of the larger NHIS.

Researchers assigned pain severity using an approach developed by CDC investigators working with the Washington Group on Disability Statistics, which provides four categories of pain.* Among the findings of the analysis:

• An estimated 23.4 million adults (10.3 percent) experience a lot of pain.
• An estimated 126 million adults (55.7 percent) reported some type of pain in the 3 months prior to the survey.
• Adults in the two most severe pain groups were likely to have worse health status, use more health care, and suffer from more disability than those with less severe pain. However, approximately half of individuals with the most severe pain still rated their overall health as good or better.
• There were associations between pain severity and race, ethnicity, language preference, gender, and age. Women, older individuals, and non-Hispanics were more likely to report any pain, while Asians were less likely.
• Minorities who did not choose to be interviewed in English are markedly less likely to report pain.
• The impact of gender on pain varies by race and ethnicity.

“This report begins to answer calls for better national data on the nature and extent of the pain problem,” said Richard L. Nahin, Ph.D., M.P.H., lead epidemiologist for NCCIH and author of the analysis. “The experience of pain is subjective. It’s not surprising then that the data show varied responses to pain even in those with similar levels of pain. Continuing analyses of these data may help identify subpopulations that would benefit from additional pain treatment options.”

Read more about the report: https://nccih.nih.gov/research/statistics/NHIS/2012/pain/severity.

*This approach was developed by Kristen Miller and Mitch Loeb of the CDC’s National Center for Health Statistics while working with of the Washington Group on Disability Statistics.

NIH produces product with fungal contamination

NIH suspends operations in its Clinical Center Pharmaceutical Development Section

June 7, 2015

Correction: On June 4, NIH stated that operations at the Pharmaceutical Development Section (PDS) at the NIH Clinical Center had been suspended. All production of sterile materials in the PDS has indeed been suspended. However, production of other materials, which were not the focus of concern and do not require sterile manufacturing practices, will continue.

The National Institutes of Health (NIH) Clinical Center has suspended operations of its Pharmaceutical Development Section (PDS) due to the discovery of serious manufacturing problems and lack of compliance with standard operating procedures. Upon receipt of a complaint, Food and Drug Administration (FDA) representatives inspected the PDS between May 19 and May 29, and found a series of deficiencies that will require the NIH Clinical Center to take a number of corrective actions.

The facility makes products for certain clinical research studies conducted in the hospital and collaborating facilities. In April, two vials of albumin, used for the administration of the drug interleukin in experimental studies, were found to have fungal contamination. Vials made from the same batch were administered to six patients, although it is unknown whether those or other vials were contaminated. The six patients have been notified and are being followed closely for any signs of infection. At this time, none has developed signs of infection or illness.

“This is a distressing and unacceptable situation,” said NIH Director Francis S. Collins, M.D., Ph.D. “The fact that patients may have been put in harm’s way because of a failure to follow standard operating procedures in the NIH Clinical Center’s Pharmaceutical Development Section is deeply troubling. I will personally oversee the steps to protect the safety of patients and remedy the situation as swiftly as possible.”

Among the problems the FDA identified in their inspection were deficiencies in the physical facility, including flaws in the air handling system, and operational failures including inadequate quality control, insufficient employee training, and lack of compliance with standard operating procedures. Deficiencies of lesser significance were identified in the Clinical Center Pharmacy. The FDA inspection reports are available here: http://www.cc.nih.gov/phar/pdfs/483.pdf (PDF - 1.31KB).

The following steps are being taken immediately to protect patients:

1. Operations of The Pharmaceutical Development Section have been suspended and no products will be made or distributed until all problems are fully understood and corrected. Materials produced by the Section are being systematically tested for contamination.
2. Of the participants in the 46 studies that are potentially affected, approximately 250 are currently scheduled to receive products manufactured by the PDS. NIH has notified the individual principal scientists responsible for each of those protocols, and is in the process of notifying the participants in these protocols. The vast majority of these patients are not immediately due for treatment and NIH is working to secure alternative sources for the products.
3. An external group of experts in microbiology and sterile manufacturing practices will be appointed to conduct a thorough review, including an assessment of all standard operating procedures, policies, staffing, and training, and make recommendations to the NIH director on the corrective actions required.
4. In addition to the immediate steps NIH is taking, it will provide an interim corrective action plan to the FDA by Friday, June 19, 2015.

“Our first responsibility is the safety and care of our patients,” said Dr. Collins. “NIH leadership is determined to identify and correct all of the deficiencies that have led to this situation.”

Over-The-Counter Allergy Drug Treats Hepatitis C in Mice

Hepatitis C is an infectious disease caused by a virus that attacks the liver. Approximately 75% to 85% of people who become infected with hepatitis C virus (HCV) develop chronic infection, as their body is unable to get rid of the virus. Worldwide, about 185 million people are estimated to have chronic hepatitis C. Left untreated, it can cause severe liver disease or liver cancer. In some cases, a liver transplant may be needed.

More than 3 million people in the United States are estimated to have chronic hepatitis C virus infection. Most people don’t know they are infected because they don’t look or feel sick. Image credit: xrender/Thinkstock.

Currently, there is no vaccine to prevent hepatitis C infection. Several treatments are available that can cure the disease. However, the drugs have side effects and can cost tens of thousands of dollars.

A team led by Dr. T. Jake Liang set out to find treatment options that are effective, safe, and affordable. Their strategy was to search for drugs already approved for other uses by the U.S. Food and Drug Administration that might have anti-HCV activity. Finding alternative uses for approved compounds significantly reduces the time, money, and effort needed to develop a new drug.

The group screened a comprehensive library of approved drugs developed by NIH’s National Center for Advancing Translational Sciences (NCATS) for the ability to block the hepatitis C virus from infecting cells and replicating. The research was conducted at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) on the NIH campus in Bethesda, Maryland. The findings were published online on April 8, 2015, in Science Translational Medicine.

The researchers identified multiple allergy-relieving antihistamines that also have antiviral activity. Among them was an over-the-counter drug called CCZ, approved in the 1940s to treat allergy symptoms.

The researchers found that the drug inhibited HCV infection of human liver cells. The drug also inhibited HCV infection in mice implanted with human liver cells.  Mice treated for 4 to 6 weeks had reduced levels of the virus, with no evidence of drug resistance.

“Although hepatitis C is curable, there is an unmet need for effective and affordable medication. CCZ is a promising candidate for part of a treatment regimen for this potentially life-threatening disease,” Liang says. However, he cautions, “People should not take CCZ to treat their hepatitis C until it has been demonstrated that CCZ can be used safely and effectively for that purpose.”

The researchers will now study how CCZ affects humans. People with hepatitis C who are interested in participating in clinical research on CCZ may call 1-866-444-2214 (TTY 1-866-411-1010) or visitwww.clinicaltrials.gov (Clinical Trial # NCT02118012) for information.

NIH study finds genetic link for rare intestinal cancer

Heredity accounts for up to 35 percent of small intestinal carcinoid, a rare digestive cancer, according to findings from a team at the National Institutes of Health. The researchers examined families with a history of the disease. Because the disease has long been considered randomly occurring rather than inherited, people with a family history are not typically screened. Results were published recently in Gastroenterology

“Small intestinal carcinoid tumors usually grow slowly without symptoms. It is often too late to reverse the condition once people seek medical attention,” said lead author Stephen Wank, M.D., senior investigator at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which supported the trial. “Our findings suggest that people with a family history of the disease should be screened for it. We hope this research empowers thousands of at-risk people with a way to prevent these tumors from becoming a devastating disease.”

Conducted at the NIH Clinical Center, the study screened 181 people from 33 families, each with at least two cases of small intestinal carcinoid. The researchers discovered the disease in 23 people who had not yet developed symptoms, and successfully removed all tumors in 21 of those people.

Genetic linkage analysis revealed a target DNA region shared by all affected members of a particularly large family. Genome sequencing narrowed that finding to a gene defect passed from one generation to the next, suggesting that the gene is an inherited risk factor for the disease. “Studying entire families gave us a unique insight into the genetic factors that can increase risk of small intestinal carcinoid,” said Wank.

“This innovative study embodies NIH’s unmatched leadership in rare disease research,” said NIDDK Director Griffin P. Rodgers, M.D. “Our new understanding of small intestinal carcinoid tumors gives scientists and health care providers a stronger platform to continue to develop proactive approaches in treatment, diagnosis and prevention.”

About 30,000 Americans have small intestinal carcinoid tumors. Like most cancers, early treatment greatly increases survival rates and quality of life. People with a family history of small intestinal carcinoid interested in joining NIH genetic studies may call 1-866-444-2214 or visit http://www.clinicaltrials.gov (Clinical Trial # NCT00646022 for information.

NIH begins early human clinical trial of Ebola vaccine

Human testing of a second investigational Ebola vaccine candidate is under way at the National Institutes of Health’s Clinical Center in Bethesda, Maryland.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) are conducting the early phase trial to evaluate the vaccine, called VSV-ZEBOV, for safety and its ability to generate an immune system response in healthy adults who are given two intramuscular doses, called a prime-boost strategy. The Walter Reed Army Institute of Research (WRAIR) is simultaneously testing the vaccine candidate as a single dose at its Clinical Trials Center in Silver Spring, Maryland.

“The need for a vaccine to protect against Ebola infection is urgent,” said NIAID Director Anthony S. Fauci, M.D. “NIH welcomes the opportunity to collaborate with the U.S. Department of Defense to conduct human clinical tests of another promising — and hopefully, successful — Ebola vaccine candidate.”

NIAID researchers include principal investigator Richard T. Davey, M.D., and co-investigator John Beigel, M.D., of NIAID’s Division of Intramural Research, Early human testing of another investigational Ebola vaccine co-developed by NIAID and GlaxoSmithKline (GSK) began in early September. Initial data on safety and immunogenicity (the capacity to generate an immune response) from clinical trials of the NIAID/GSK Ebola vaccine are expected by the end of 2014.

The VSV-ZEBOV vaccine candidate was developed by researchers at the Public Health Agency of Canada’s National Microbiology Laboratory. It has been licensed to NewLink Genetics Corp through its wholly owned subsidiary BioProtection Systems, both based in Ames, Iowa.

“Canada has long been a world leader in Ebola research and innovation. Scientists at Canada's National Microbiology Lab developed this Ebola vaccine, following years of hard work. We hope the clinical trial at the National Institutes of Health proves to be safe and effective, so that the Canadian Ebola vaccine can be used as a global resource to help save lives and end this complex outbreak in West Africa," said Canada’s Minister of Health Rona Ambrose.

VSV-Zebov is based in part on a genetically engineered version of vesicular stomatitis virus (VSV), which primarily affects rodents, cattle, swine and horses. Human VSV infections are rare and generally produce three to four days of mild illness. In the VSV-ZEBOV investigational vaccine, the gene for the outer protein of the vesicular stomatitis virus has been replaced with a segment of the gene for the outer protein of the Zaire Ebola virus species. The investigational VSV-ZEBOV vaccine cannot cause a vaccinated individual to become infected with Ebola.

The NIH Phase 1 clinical trial of the VSV-ZEBOV vaccine candidate will enroll 39 healthy adults aged 18 to 65 years. Participants will be randomly assigned to one of three groups with 13 participants each. In each group, 10 participants will receive the investigational VSV-ZEBOV vaccine; three will receive a placebo. Each of the three groups will receive a different, escalating dose of the investigational vaccine, with the first group enrolled receiving the lowest dose and the third group enrolled receiving the highest dose. Study participants will receive an injection of the VSV-ZEBOV vaccine or placebo at their first scheduled visit and again, at the same dosage level, 28 days later.

Enrollment at each dosing level is staggered, so interim safety assessments of vaccinated individuals can be conducted before moving to the next dosing level. All study participants will be seen and evaluated by clinical staff 11 times over one year.

While NIAID tests the VSV-ZEBOV vaccine candidate as a prime-boost strategy,  WRAIR is evaluating the investigational vaccine as a single injection. This is being done to evaluate in real time the safety profile of the investigational vaccine when provided at different dosages and compare the immune responses induced by one injection versus two injections. Initial safety and immune response data on the VSV-ZEBOV vaccine are expected by the end of 2014.

More information about the NIAID clinical trial of the investigational VSV-ZEBOV Ebola vaccine is available on the NIH Clinical Center website using the protocol number 15-I-0001.

Patient with exposure to Ebola has arrived safely at NIH Clinical Center in America

A patient with exposure to the Ebola virus in Sierra Leone has been transferred from an overseas location and admitted to the NIH Clinical Center for observation and to enroll in a clinical protocol. The patient arrived at the NIH Clinical Center on Sunday, September 28, at approximately 4 p.m. ET.

The patient is an American physician who was volunteering services in an Ebola treatment unit in Sierra Leone.

Out of an abundance of caution, the patient has been admitted to the NIH Clinical Center’s special clinical studies unit that is specifically designed to provide high-level isolation capabilities and is staffed by infectious diseases and critical care specialists. The unit staff is trained in strict infection control practices optimized to prevent spread of potentially transmissible agents such as Ebola.

No additional details about the patient are available at this time.

NIH is taking every precaution to ensure the safety of our patients, NIH staff, and the public. This situation presents minimal risk to any of them.

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, visit www.nih.gov.

NIH to Launch Human Safety Study of Ebola Vaccine

Trial is First in Series of Accelerated Safety Studies of Ebola Vaccines

Initial human testing of an investigational vaccine to prevent Ebola virus disease will begin next week by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The early-stage trial will begin initial human testing of a vaccine co-developed by NIAID and GlaxoSmithKline (GSK) and will evaluate the experimental vaccine’s safety and ability to generate an immune system response in healthy adults. Testing will take place at the NIH Clinical Center in Bethesda, Maryland.

The study is the first of several Phase 1 clinical trials that will examine the investigational NIAID/GSK Ebola vaccine and an experimental Ebola vaccine developed by the Public Health Agency of Canada and licensed to NewLink Genetics Corp. The others are to launch in the fall. These trials are conducted in healthy adults who are not infected with Ebola virus to determine if the vaccine is safe and induces an adequate immune response.

In parallel, NIH has partnered with a British-based international consortium that includes the Wellcome Trust and Britain’s Medical Research Council and Department for International Development to test the NIAID/GSK vaccine candidate among healthy volunteers in the United Kingdom and in the West African countries of Gambia (after approval from the relevant authorities) and Mali.

Additionally, the U.S. Centers for Disease Control and Prevention has initiated discussions with Ministry of Health officials in Nigeria about the prospects for conducting a Phase 1 safety study of the vaccine among healthy adults in that country.

The pace of human safety testing for experimental Ebola vaccines has been expedited in response to the ongoing Ebola virus outbreak in West Africa. According to the World Health Organization (WHO), more than 1,400 suspected and confirmed deaths from Ebola infection have been reported in Guinea, Liberia, Nigeria, and Sierra Leone since the outbreak was first reported in March 2014.

“There is an urgent need for a protective Ebola vaccine, and it is important to establish that a vaccine is safe and spurs the immune system to react in a way necessary to protect against infection,” said NIAID Director Anthony S. Fauci, M.D. “The NIH is playing a key role in accelerating the development and testing of investigational Ebola vaccines.”

“Today we know the best way to prevent the spread of Ebola infection is through public health measures, including good infection control practices, isolation, contact tracing, quarantine, and provision of personal protective equipment,” added Dr. Fauci. “However, a vaccine will ultimately be an important tool in the prevention effort. The launch of Phase 1 Ebola vaccine studies is the first step in a long process.”

“Tried and true public health interventions, strong supportive medical care and the rapid testing of Ebola vaccines and antiviral treatments can help to reduce suffering now and in the future,” said CDC Director Thomas R. Frieden, M.D., M.P.H.

The investigational vaccine now entering Phase 1 trials was designed by Nancy J. Sullivan, Ph.D., chief of the Biodefense Research Section in NIAID’s Vaccine Research Center (VRC). She worked in collaboration with researchers at the VRC, the U.S. Army Medical Research Institute of Infectious Diseases, and Okairos, a Swiss-Italian biotechnology company acquired by GSK in 2013.

Phase 1 clinical trials are the first step in what is typically a multi-stage clinical trials process). During Phase 1 studies, researchers test an investigational vaccine in a small group of people to evaluate its safety and the immune response it provokes. Phase 2 clinical trials of investigational vaccines are designed to further assess safety and immune response in larger numbers of volunteers. Under certain circumstances, the vaccine’s ability to prevent infection or disease (called efficacy) can be determined in a Phase 2 trial. Phase 3 clinical trials are directed predominantly at determining efficacy.

The NIAID/GSK Ebola vaccine candidate is based on a type of chimpanzee cold virus, called chimp adenovirus type 3 (ChAd3). The adenovirus is used as a carrier, or vector, to deliver segments of genetic material derived from two Ebola virus species: Zaire Ebola and Sudan Ebola. Hence, this vaccine is referred to as a bivalent vaccine. The Zaire species of the virus is responsible for the current Ebola outbreak in West Africa.

The vaccine candidate delivers one part of Ebola’s genetic material to human cells, but the adenovirus vector does not replicate. Rather, the Ebola gene that it carries allows the cells of the vaccine recipient to express a single Ebola protein, and that protein prompts an immune response in the individual. It is important to know that the Ebola genetic material contained in the investigational vaccine cannot cause a vaccinated individual to become infected with Ebola.

“The experimental NIAID/GSK vaccine performed extremely well in protecting nonhuman primates from Ebola infection,” Dr. Fauci noted.

The candidate vaccine builds upon three earlier NIAID-developed investigational Ebola vaccines that began Phase 1 clinical trial testing in 2003.

“The knowledge gained from each of those trials has contributed to the development of the candidate vaccine we are now studying, as well as our improved understanding of human immune responses to investigational Ebola vaccines,” said John R. Mascola, M.D., director of NIAID’s Vaccine Research Center.

The Phase 1 clinical trial, called VRC 207, will be led by principal investigator Julie E. Ledgerwood, D.O., chief of the VRC’s clinical trials program, and will be conducted among 20 healthy adults ages 18 to 50 years. Participants will be divided into two groups of 10 participants each. One group will receive an intramuscular injection of the NIAID/GSK experimental vaccine. The second group will receive a single injection of the same vaccine but at a higher dose.

A number of safety features are built into the study’s design, including daily and weekly reviews of patient data by clinical staff and the study protocol team. Additionally, the trial features a staged enrollment plan that requires interim safety reviews after three participants have been vaccinated and have undergone three days of follow up before enrolling additional study participants into the group. Participants in both groups will be seen and evaluated by clinical staff nine times over a 48-week period.

Additional Phase 1 Tests of the NIAID/GSK Vaccine

As part of the VRC 207 trial, NIAID will also test a version of the NIAID/GSK vaccine that contains genetic material from only the Zaire Ebola species. Hence, this vaccine is referred to as a monovalent vaccine. This portion of the Phase 1 safety study, which will also involve 20 healthy adults, is expected to begin in October at the NIH Clinical Center and potentially another U.S. location. Dr. Ledgerwood will also lead that effort. The VRC 207 clinical trial is being conducted based on expedited review and approval by the U.S. Food and Drug Administration.

In parallel, NIH has partnered with an international consortium that includes the British-based Wellcome Trust, as well as Britain’s Medical Research Council and Department for International Development to test the same NIAID/GSK monovalent vaccine candidate. The vaccine candidate will be tested among 60 healthy volunteers at the University of Oxford in England and among 40 healthy volunteers in Mali by the University of Maryland School of Medicine Center for Vaccine Development and its Center for Vaccine Development in Mali (a joint enterprise of the University of Maryland School of Medicine and the Ministry of Health of Mali). Additionally, the vaccine candidate is expected to be tested among 40 healthy volunteers in Gambia after approval from the relevant authorities.

The Oxford trial is expected to launch in mid-September pending ethical and regulatory approval.

“Today’s announcement shows how private and public partners can pull together to quickly respond to this critical public health emergency. Developing a new vaccine is complex with no guarantees of success, and we are still in the early days for our Ebola vaccine candidate. But we are encouraged by progress so far and will do the best we can, along with WHO and our partners, to speed up development and explore ways in which the vaccine could contribute to this or future Ebola outbreaks,” said Dr. Moncef Slaoui, chairman of Global R&D and Vaccines at GSK.

Initial safety and immunogenicity data from the Phase 1 trials of the NIAID/GSK investigational Ebola vaccine are expected in late 2014.

Vesicular Stomatitis Virus (VSV) Ebola Vaccine Testing

The NIH will also collaborate with the U.S. Department of Defense in support of efforts by NewLink Genetics Corp., a biopharmaceutical company in Ames, Iowa, to conduct Phase 1 safety studies of the investigational recombinant vesicular stomatitis virus Ebola vaccine (called VSV-EBOV) developed by and licensed from the Public Health Agency of Canada. Those clinical trials are expected to begin in the fall at the Clinical Trials Center of Walter Reed Army Institute of Research in Silver Spring, Maryland.

For more information about these early-stage Ebola vaccine clinical trials, see Questions and Answers: Phase 1 Clinical Trials of NIAID/GSK Investigational Ebola Vaccine.