New model proposed for clinical trials – E2E trials

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Experts across academia, industry and government propose a new method for health care providers to get the right treatments to the right patients at the right time. This new approach, A Proposal for Integrated Efficacy-to-Effectiveness (E2E) Clinical Trials, published in Nature Clinical Pharmacology & Therapeutics, recommends a seamless transition from controlled experiments to real-world comparative effectiveness trials. This continuum will improve the accuracy of treatment selection and better determine how those treatments work on different groups of people.

Efficacy trials are conducted in optimal conditions with patients who have similar characteristics. These trials are typically used to secure regulatory approval for a drug.

Effectiveness trials are conducted in more typical clinical settings, with patients who have varying characteristics. These trials are designed to determine whether treatment effects identified in efficacy trials carry over to more typical uses of drugs in practice.

Currently, efficacy and effectiveness trials are conducted separately, and effectiveness trials may occur years later or not at all. In the E2E model, an effectiveness trial starts immediately after the efficacy trial is completed (or as soon as possible, depending upon a predetermined approval process). Data derived from the efficacy trial can be used to formulate questions to investigate during the effectiveness trial; data derived from the effectiveness trial can then be used to assist patients and providers in making individual treatment decisions.

Development of the E2E approach was led by Harry P. Selker, MD, MSPH of Tufts Clinical and Translational Science Institute (CTSI) and Tufts Medical Center’s Institute for Clinical Research and Health Policy Studies (ICRHPS), with assistance from Aaron Kirby, MSc, Tufts CTSI’s Manager of Project Administration. The research team includes:

“The E2E approach represents a fundamental shift in a drug development model that has remained basically unchanged for over fifty years,” suggests Kenneth I. Kaitin, PhD, director of the Tufts Center for the Study of Drug Development and research professor at Tufts University School of Medicine. “Although adoption of the approach is not without its challenges, there are likely to be many winners: industry, who will gain better understanding of a drug’s utility, enabling differentiation from competitors; regulators, who will have greater understanding of the drug’s safe and effective use in heterogeneous populations; payers, who will be able to make more informed reimbursement and coverage decisions; and of course physicians and patients, who will benefit from real-world data on the benefits and risks of new medicines.”

“There is growing realization that the difference between efficacy and effectiveness is not just a challenge for drug regulation, but also an underutilised learning opportunity,” says Hans-Georg Eichler, MD, MSc, of European Medicines Agency, “the heterogeneity of real-life treatment populations may help identify non-responders or non-tolerators, and such insights may not be gained from the rather homogenous clinical trial populations. Realizing this learning opportunity will require pre-planned and cost-effective studies: the E2E trial may be exactly what’s needed.”

The authors hope practitioners will consider the E2E model for future trials.



Duchenne muscular dystrophy may be treated with erectile dysfunction drug

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Approximately 1 in every 3,600 male infants worldwide is affected by Duchenne muscular dystrophy – an inherited condition that causes severe muscle weakness. At present, there is no specific treatment for the disease. But new research published in the journal Neurology suggests that certain drugs usually prescribed for erectile dysfunction may be effective.

Duchenne muscular dystrophy (DMD) is caused by a defective gene for dystrophin – a protein that helps maintain healthy muscles. Low levels or absence of dystrophin means the muscles lack nitric oxide – a chemical that signals blood vessels to dilate during exercise so blood flow can increase.

As a result of the way the gene is inherited, the condition primarily affects boys and young men. Onset of the disease usually occurs before the age of 6 years. As well as muscle degeneration, the condition can cause intellectual disability, congestive heart failure or irregular heart rhythm, back and chest deformities and respiratory disorders.

Many individuals with DMD are treated with corticosteroids. This medication can help to slow muscle degeneration and reduce negative effects on the heart and lung.

But the researchers of this study, including Dr. Ronald G. Victor of the Cedars-Sinai Heart Institute in Los Angeles, CA, note that corticosteroids cause an array of side effects and more than 75% of patients are unable to endure them.

With this in mind, the team set out to determine whether the drugs sildenafil (Viagra) or tadalafil (Cialis) could help treat DMD. Both drugs are commonly used to treat erectile dysfunction and pulmonary arterial hypertension. They work by relaxing blood vessels, therefore increasing blood flow.

Drugs improved blood flow in boys with DMD

For their study, the team assessed 10 boys aged between 8 and 13 years who had DMD. All boys were taking corticosteroids and were able to walk, although some often used a wheelchair or scooter to help with mobility.

The blood flow in the muscles of these participants was measured as they carried out a handgrip exercise and when they were resting.

Their blood flow was compared with 10 similarly aged healthy boys, which confirmed that those with DMD had abnormal blood flow, even when taking corticosteroids.

The boys with DMD were then required to take each drug – sildenafil or tadalafil – 2 weeks apart. Their blood flow was measured again as they rested and carried out a handgrip exercise, and this was compared with the blood flow of the 10 healthy boys.

The researchers found that after taking each drug, the boys with DMD had the same blood flow response as the healthy boys during exercise. The team notes that this result was instantaneous and was more pronounced when the drug was given in higher doses.

Dr. Victor notes that although a lot more research is to be done before either drug can be recommended for individuals with DMD, the team’s findings are encouraging. “This is not a cure, but it is the first stop toward identifying potential treatments,” he adds.

However, the researchers say their study has limitations. For example, they note that it is unknown whether long-term use of either drug can maintain improved blood flow.


Health ministry to amend D and C Rules to assign NIB as apex national lab for more products

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The Union health ministry is amending the Drugs and Cosmetics Rules to make the National Institute of Biologicals (NIB), based in Noida here, as the apex national laboratory for several products like blood products and diagnostic kits with a view to ensure high level quality for these products in the market.

The Ministry has prepared a draft notification to amend the rule, in accordance with the recommendations by the Drugs Technical Advisory Board (DTAB). The rule, published for the comments from the stakeholders, will come into effect with the final notification after the mandatory period of 45 days.

“These rules may be called the Drugs and Cosmetics (Sixth Amendment) Rules, 2014. In the Drugs and Cosmetics Rules, 1945, in rule 3A, for sub-rule (8), the following sub-rule shall be substituted, namely:- “(8) The functions of the Laboratory in respect of the following kits or class of drugs shall be carried out at the National Institute of Biologicals and the functions of the Director in respect of the said drugs or class of drugs shall be exercised by the Director of the said institute,” said the notification.

The products named under the rule are blood grouping reagents, diagnostic kits for human immunodeficiency virus, hepatitis B surface antigen and hepatitis C, among others. The blood products include human albumin,  human normal immunoglobulin (intramuscular & intravenous),  human coagulation factor VIII, human coagulation factor IX, plasma protein fractionation, fibrin sealant kit, and anti Inhibitor coagulation complex.

The rules also listed recombinant products like recombinant insulin and insulin analogues, r- erythropoietin (EPO) and  r-Granulocyte colony stimulating factor (G-CSF). Besides, biochemical kits like glucose test strips and fully automated analyser based glucose reagents are also included.

NIB, an autonomous institution under the Ministry of Health & Family Welfare,  is a premier scientific organisation and a centre of excellence to ensure quality of biologicals and vaccines in the country. The institute reviews the quality of biological products available through domestic manufacturers or imports with the help of a state-of-the-art facility.

Source: PharmaBiz

BayerHealthCare to share clinical trial data through internet portal

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Bayer HealthCare announced that it will start sharing data from its clinical studies through the internet portal From now on, qualified researchers can request anonymised patient-level data from Bayer HealthCare sponsored clinical studies listed on the website.

By joining the portal, Bayer HealthCare is supporting efforts of the European Medicines Agency (EMA) to increase the transparency of data from clinical studies. As a member company of the pharmaceutical trade associations EFPIA and PhRMA, Bayer is following their declared principles on responsible clinical trial data sharing.

“Our commitment to clinical trial transparency reflects our will to foster scientific research and hence public health,” said Dr Joerg Moeller, member of the Bayer HealthCare Executive Committee and Head of Global Development. “Joining the electronic platform and providing access to anonymized patient-level data, protocols and clinical study reports is a further step towards increased transparency while maintaining patient privacy.”

Secured data access will be granted after approval of the research proposal by an independent scientific review panel. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 1, 2014. Bayer HealthCare is not involved in the decisions made by the independent scientific review panel. Bayer HealthCare will take all necessary measures to ensure that patient privacy is safeguarded, in accordance with applicable laws and regulations.

In addition to the data provided via, Bayer HealthCare provides through its ‘Bayer Trial Finder’ available at information about Bayer HealthCare sponsored trials dating back to 2005. This public information first becomes available at the beginning of a clinical study and is updated throughout the conduct of the study. Generally, summaries of trials will be published within a year of study completion.

The joint EFPIA-PhRMA Principles for Responsible Clinical Trial Data Sharing are available at:

Source: PharmaBiz

USFDA Alerts: Changes to the Edurant (rilpivirine) label

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On May 1, 2014, FDA  approved changes to the Edurant (rilpivirine) label to include drug-drug interaction with rilpivirine and metformin and rilpivirine and rifabutin.
Under section 2 Dosage and Administration:
Rifabutin Co-administration:
For patients concomitantly receiving rifabutin, the EDURANT dose should be increased to 50 mg (two tablets of 25 mg each) once daily, taken with a meal.  When rifabutin co‑administration is stopped, the EDURANT dose should be decreased to 25 mg once daily, taken with a meal.
Rilpivirine did not have a clinically significant effect on the pharmacokinetics of metformin.
The complete revised label is available at Drugs@FDA.
Edurant is a member of the Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) class of antiretroviral drugs, marketed by Tibotec Therapeutics.
Source: USFDA