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Crohn's disease is an ongoing condition that causes inflammation of the digestive tract, or the GI (gastrointestinal) tract (the gut).
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Recent policy changes emphasize the need for sponsoring organizations to be even more vigilant in establishing, updating and monitoring their systems for compliance with clinical research requirements, whether conducted domestically or in a foreign locale.Both the European Medicines Agency (EMEA) and the U.S. Food and Drug Administration (FDA) have taken recent actions, jointly and independently, that demonstrate an increasing focus on safety and enforcement issues with clinical research. The recent changes announced by the FDA and EMEA demonstrate a renewed concern and greater emphasis on regulatory controls and procedures, particularly with regard to adherence to Good Clinical Practice (GCP) requirements for clinical trials conducted outside of the European Union and United States. Nevertheless, both agencies are attempting to accomplish these changes with maximum cooperation and minimum disruption to industry.
Discussion
FDA Reforms
In May 2009, Deborah Autor, director of the FDA's Center for Drug Evaluation and Research (CDER) Compliance Office, was quoted as saying, "In today's rapidly changing environment, complacency is not an option . . . I do predict more action. Tell your clients and companies to get going." Recent actions by FDA have supported this prediction and could be interpreted as evidence of a new FDA policy focusing on increased safety and enforcement in clinical research.On August 10, 2009, the FDA announced that it would make changes to the manner in which the FDA disciplines medical researchers who violate federal regulatory requirements, announcing that it would modify procedures to permit the agency to process such actions faster. The FDA has designated an administrative law judge to serve as presiding officer for administrative hearings of researcher misconduct, assigned the Good Clinical Practice Program office to oversee disqualification proceedings and assigned dedicated staff to debarment proceedings. Several members of the U.S. House of Representatives Committee on Energy and Commerce, the committee with principal FDA oversight, have also requested that the U.S. Government Accountability Office (GAO) examine FDA's debarment and disqualification procedures, although GAO has yet to release this report.At a presentation to the Food and Drug Law Institute in Washington, D.C., on August 6, 2009, FDA Commissioner Margaret Hamburg cited enforcement of the law as "critical to the agency's public health mission," and announced six "initial steps to strengthen enforcement at the FDA." Each of these steps is directed at improving the ability to more effectively and quickly address potential violations of FDA laws and regulations. Specifically, Commissioner Hamburg announced the following steps:
As a carrot to encourage quicker remedial action by recipients of warning letters, FDA will establish a "close-out" process, whereby an organization that has received a warning letter that has been determined by FDA to have corrected the violations, usually through re-inspection, may be issued a "close-out" letter indicating that the issues in the warning letter have been successfully addressed.
EMEA Reforms
The EMEA has indicated within recent publications that it also intends to pay increased attention to enforcement issues relating to researcher misconduct, specifically relating to GCP compliance, in the coming years. EMEA has expressed a specific intent to target GCP compliance issues with regard to clinical trials conducted in non-EU countries where the data is used to support applications for marketing authorization in the European Union. Moreover, the EMEA has stated within its Work Plans that it intends to continue to focus on enforcement activities related to GCP compliance.The EMEA Strategy Paper titled "Acceptance of Clinical Trials Conducted in Third Countries, for Evaluation in Marketing Authorisation Applications," issued on December 5, 2008, announced the intention of the EMEA to address a "growing concern . . . about how well these [clinical] trials are conducted from an ethical and scientific/organizational standpoint (including GCP compliance) and about the available framework for the supervision of these trials." Within the Strategy Paper, it states that the "EMEA Work Programmes for 2008 and 2009 set out a number of actions relating to clinical trials conducted in third countries," including verification of GCP and ethical compliance at the time of evaluation of the data, greater transparency of the evaluation process and increased GCP inspection for clinical trials performed outside the European Union. The Strategy Paper sets forth a three-year plan of activities for December 2008 to December 2010 to address pre-authorization, concurrent review during application and post-authorization monitoring of compliance with clinical development processes.Moreover, the EMEA Work Plan for GCP Inspectors Working Group for 2009, issued January 2009, states that one of its three priorities is to "[d]evelop processes and capacity building in relation to GCP and inspections of clinical trials conducted in third countries." This provides further support for the EMEA's increased attention to GCP and other research noncompliance issues, particularly with regard to clinical trials data gathered in non-EU countries.
EMEA-FDA GCP Initiative
In addition to other activities the FDA and EMEA have undertaken independently to address research misconduct and GCP compliance, both agencies have recently undertaken a new cooperation initiative to conduct joint inspections and share information about clinical research data. On July 31, 2009, the EMEA and the FDA announced that they have jointly agreed to launch the EMEA-FDA GCP Initiative. The Initiative is a joint effort between the CDER and the EMEA to "ensure that clinical trials submitted in drug marketing applications in the United States and Europe are conducted uniformly, appropriately, and ethically."The Initiative will be governed by the confidentiality agreement between the EMEA and the FDA announced on September 12, 2003, which permits sharing of pre- and post-approval regulatory information about medicinal products subject to evaluation or authorized under the centralized procedure, including regulatory issues, scientific advise, orphan drug designation, inspection report, marketing approvals and post-authorization surveillance information. See Public Statement, "EU-FDA Bilateral Meeting."The Initiative will have three key objectives:
The Initiative is planned to begin with an 18-month pilot phase, beginning on September 1, 2009, that is limited in scope to consideration of those products regulated by CDER (over-the-counter and prescription drugs, including biological therapeutics and generic drugs) and/or the EMEA under EU centralized procedures (human medicines derived from biotechnology processes, such as genetic engineering; advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines; medicines intended for the treatment of HIV/AIDS, cancer, diabetes, neurodegenerative disorders, autoimmune diseases and other immune dysfunctions, or viral diseases; and officially designated "orphan medicines," or medicines used for rare diseases). Once the pilot phase is completed, the EMEA and FDA will jointly assess the results of the pilot and develop an amended process and scope for the fully implemented Initiative.The Initiative marks a significant step towards the continuing globalization of regulation of human medicines and the adoption of GCP as an international standard for conducting clinical trials. For example, on April 28, 2008, the FDA announced revised guidance on the standards under which the agency will accept data from foreign clinical trials in support of domestic applications and submissions. 73 Fed. Reg. 22800, 22812 (Apr. 28, 2008). The FDA's revised regulations now require foreign clinical trials used as support for an investigational new drug, a new drug approval or an abbreviated new drug approval application be conducted in compliance with GCP regulations.
Conclusion
The recent actions of the FDA and the EMEA with regard to increased attention to clinical research misconduct and compliance with GCP demonstrate an increased focus on enforcement activities relating to safety issues in clinical research. Both the FDA and EMEA have shown through recent policy changes and announcements that they both intend to pay closer attention to whether clinical research is being conducted in an ethical manner and in compliance with regulatory requirements and GCP principles. Nevertheless, both agencies have made it clear that they intend to accomplish their goals while attempting to cooperate with industry needs for prompt action and resolution of issues.These policy changes emphasize the need for sponsoring organizations to be even more vigilant in establishing, updating and monitoring their systems for compliance with clinical research requirements, whether conducted domestically or in a foreign locale. Sponsoring organizations must ensure, and be in a position to demonstrate, compliance with international standards of practice such as GCP, as well as compliance with additional requirements that relate to the location (e.g., the United States or the European Union) of the submission for marketing approval.
Source: http://www.mondaq.com/article.asp?articleid=85460
Hi,
Found an article on practical aspects of conducting clinical trials in inida.
Regards
Ramakrishna
What might become the first drug derived from human stem cells failed in two late-stage clinical trials, dealing a setback to the drug’s developer and to the stem cell field.
The developer, Osiris Therapeutics, said Tuesday that its drug, Prochymal, was no more effective, over all, than a placebo in treating a life-threatening complication of bone marrow transplantation, though certain patients seemed to be helped.
Shares of Osiris, which is based in Columbia, Md., fell 34 percent, to $8.03.
Prochymal is a preparation of mesenchymal stem cells, which are obtained from the bone marrow of healthy young adults.
Because the cells are derived from adults, they sidestep the ethical issues stemming from the destruction of human embryos needed to make embryonic stem cells. Unlike most other types of adult stem cells, mesenchymal cells grow well in culture, so thousands of doses can be produced from a single donation.
Stem cells, particularly in the form of bone marrow transplants, are already used in medicine. Osiris is hoping that Prochymal will become the first stem cell product approved by the Food and Drug Administration and sold as a mass-produced pharmaceutical product.
But the failure in the two trials could make it hard to reach that goal. Both trials tested Prochymal as a treatment for graft-versus-host disease, which occurs when immune cells in donated marrow attack the recipient’s organs as foreign tissue.
In one trial, in which Prochymal was used along with steroids, 45 percent of patients responded to Prochymal and steroids compared with 46 percent who had a response to steroid and a placebo.
In a second trial, in which Prochymal was tested in patients who were not benefiting from steroids, 35 percent of those getting the drug had a resolution of graft-versus-host disease for at least 28 days, compared with 30 percent getting the placebo. The difference was not statistically significant.
Osiris said, however, that in the second trial, the drug did provide a statistically meaningful benefit in patients having graft-versus-host disease that specifically affected their livers or their gastrointestinal tracts.
C. Randal Mills, the company’s chief executive, said he hoped the drug could be approved for those patients, given the seriousness of the disease. “Prochymal is having a clear effect in the liver, and that is the most underserved patient population,” he said in an interview.
But the F.D.A. is usually reluctant to approve a drug based on its working in only a subset of patients.
In March, Osiris stopped enrollment in a trial testing Prochymal as a treatment for Crohn’s disease, saying it was unlikely the drug would be better than a placebo, because of a high positive response to the placebo. Genzyme has the right to sell Prochymal outside the United States and Canada.
Dr. Darwin J. Prockop, an expert on mesenchymal stem cells who was not involved in the trials, said there were still a lot of unknowns about how the cells work. “Understanding it well enough to translate to the clinic — that’s the hurdle we’re at,” said Dr. Prockop, who is director of the Institute for Regenerative Medicine at Texas A&M Health Science Center.
Source: The New York Times
Hi, to allA document on feasibility for global clinical trial.
Lead author, Professor Berit Heitmann, based at Copenhagen University Hospital, says his research may help GPs identify patients who are at an increased risk of early death and developing heart disease.
While several studies have already demonstrated that being either very overweight or underweight are related to premature death and disease, this is the first to investigate the implications of thigh size on health.
Almost 3000 individuals took part in the study in Denmark - this included 1463 men and 1380 women. Participants were examined in 1987/88 for height, weight, thigh, hip and waist circumference and body composition. They were then followed up for 10 years for incidence of heart disease and 12.5 years for total number of deaths.
During the follow-up period 257 men and 155 women died, also 263 men and 140 women experienced cardiovascular disease and 103 men and 34 women suffered from heart disease. When assessing the results, the authors found that the survivors had higher fat-free thigh circumference levels.
The relationship between thigh size and early death and disease was found after taking body fat and other high risk factors (such as smoking and high cholesterol) into account. The authors therefore suggest that the risk from narrow thighs could be associated with too little muscle mass in the region. This is problematic because it may lead to low insulin sensitivity and type 2 diabetes and, in the long run, heart disease, they explain.
The authors conclude that the study "found that the risk of having small thighs was associated with development of cardiovascular morbidity and early mortality. This increased risk was found independent of abdominal and general obesity, lifestyle and cardiovascular risk factors such as blood pressure and lipids related to early cardio vascular morbidity and mortality".
The authors believe that doctors could use thigh size as an early marker for at risk patients and suggest that individuals increase lower body exercise in order to increase the size of the their thighs if necessary. Further research would be needed, however, to assess whether this approach was worthwhile.
regards
Can anybody update me on clinical trials conducted in India for Bosentas for Pulmonary Arterial Hypertension and the sites involved.
Regards,
Ocean coral 'offers pain therapy'
A compound harvested from soft coral off the coast of Taiwan could provide a new treatment for pain from intractable nerve damage, experts say.
Traditional painkillers like aspirin and even morphine often do little to take the edge off neuropathic pain.
But research in the British Journal of Pharmacology suggests Capnella imbricata, or Kenya Tree Coral, could provide relief.
The Taiwanese scientists report promising early trial results in rats.
Several important drugs have already been developed from chemicals found in coral reef organisms.
Among these is the antiviral AZT, a treatment for people with HIV, which is based on chemicals extracted from a Caribbean reef sponge.
Reefs have also yielded treatments for cardiovascular diseases, ulcers, leukaemia and skin cancer.
Deep treasures
Dr Zhi-Hong Wen and colleagues at the National Sun Yat-Sen University have been testing a chemical called capnellene, which is isolated from soft coral collected at Green Island, a small volcanic island in the Pacific Ocean about 33km off the eastern coast of Taiwan.
The reef there is said to be home to more than 200 different types of coral.
Capnellene appears to work on the supporting cells that surround nerve cells, which are thought to be responsible for neuropathic pain in some way.
Recent research suggests inflammation plays a role, and inflammation activates supporting cells like microglia to release compounds that can excite nerves carrying pain signals.
People with neuropathic pain experience severe pain from a stimulus or touch that would normally cause only slight discomfort or stimuli that would normally induce no pain at all.
Some even get unpleasant or painful feelings even when there is no stimulus.
It is estimated that about 1 in 100 people in the UK have persistent neuropathic pain - many are people with nerve damage caused by diabetes.
Dr Wen's team tested capnellene and a second very similar compound in isolated microglia cells and in experimental models of neuropathic pain in rats, with promising results.
They say more studies are now needed to see if this could offer a new way to treat the condition.
Dr Wen said: "Today there are few pharmacological agents that can help people suffering from neuropathic pain, but we believe that these marine-derived compounds could lead to the development of a new range of drugs of great potential."
Source: BBC News
Hi Jothivel Arul,
Thanks for the appropriate reply, but, were expecting the answer with some source hence, please find attached some documents on readability studies.
Sushma Naidu
Hi, Here I am attaching the article on how to create a case report form and what parameters reflects the case report form.please find it.
Thanks for the great content!
Dear All,
I would like to know what are " Readability studies"?
Can anyone help me out finding out some infromation on it !!!!!!
Thanks
Savitha
Dear Ms.Savitha,
Readability studies are nothing but the trial performed to analyse whether the patients are able to understand the information provided in the Infoemd Consent Form/Document, as well as in the Package Information Leaflets (PIL) of products for human use.
Hope, your doubt clear by now.
Jothivel Arul