Saturday, July 02, 2011

Avastin Fight Highlights Limits Of Big, Random Trials

A Food and Drug Administration special advisory panel voted 6-0 on Wednesday to withdraw approval of the drug Avastin for treating late-stage breast cancer, sticking to its usual scientific standards despite some patients' pleas to disregard them.

The recommendation was based on the best scientific evidence currently available, but the controversy highlights the limits of the science the FDA uses to determine drug effectiveness.

"Large, randomized-controlled trials are the 20th century," said Peter Pitts, president of the conservative Center for Medicine in the Public Interest. "The 21st century is the age of personalized medicine, where we need better molecular diagnostics to determine which subpopulation reacts to which treatments."

Avastin blocks the growth of new blood vessels to tumors, and is already FDA-approved for late-stage colon and lung cancer.

In 2008 the FDA granted accelerated approval of Avastin for use in late-stage breast cancer based on one randomized trial that found it slowed the progression of late-stage breast cancer.

In late 2010, the FDA withdrew approval based on two trials that found Avastin did little to slow progression, did not improve overall survival from late-stage breast cancer, and that it posed serious health risks, including death.

Randomized-controlled trials often involve large samples of patients. Such studies determine if a drug has a widespread benefit. But this is also a limitation. A treatment may work for a subpopulation in the sample, but since it doesn't work for most people in the sample, the average shows that the treatment is ineffective.

"The concept that you're looking for one magic bullet that cures a ton of patients at once is the wrong idea," said Terry Kalley, who founded Freedom of Access to Medicines in response to the FDA's 2010 decision on Avastin. "Cancer is likely to be cured by several therapies that target different subpopulations." Kalley says his wife Arlene has been taking Avastin, along with chemotherapy, for 27 months.

Roche asked the FDA to extend its approval of Avastin until it conducts a study that "would include a biomarker component to identify patients who may be more likely to derive a more substantial benefit from Avastin."

But that is in the future. "Unfortunately, the data we have right now (don't) allow us to know if there is such a subpopulation," said Karuna Jaggar, executive director of Breast Cancer Action.

Jaggar is concerned that Roche is using this as a stalling tactic to keep Avastin on the market. The Swiss drug giant could lose nearly $1 billion in sales, analysts say. "We must insist that breast-cancer patients are receiving drugs that have been demonstrated to work," Jaggar added.

Others say regulators should keep Avastin approved for now. "The FDA should say the evidence isn't there right now, but we will work with Genentech and patient groups to develop the appropriate diagnostics," said Pitts. "But the FDA needs to leave the indication on the label so people can still use it and be reimbursed for that."

If the FDA rescinds Avastin for late-stage breast cancer, at least until subpopulations are studied, then Genentech/Roche cannot market the drug for that purpose.

Doctors could still prescribe Avastin for the off-label use. But it's unlikely that government programs like Medicare and Medicaid or private insurance will cover Avastin — which costs $80,000 or more per year — for breast cancer.

An estimated 17,500 women suffer from late-stage breast cancer.

Many people like Terry testified at the hearings about Avastin. But without better data, such stories are little more than anecdotal.

The flip side is that if it turns out that Avastin does help some subpopulations, such women today will suffer as long as the FDA does not approve the drug for late-stage breast-cancer treatment.


Children risking ill health and shorter life by eating 50% too much salt every day

But only if you believe official guidelines are scientifically based. They are not. They are just a poorly-founded guess

Children are routinely eating too much salt, risking ill health and a shorter life. Typical amounts are at least 50 per cent more than the recommended daily maximum but some consume almost double.

Health experts warn that the processed foods and sauces at the heart of the nation’s diet are fuelling a dangerous daily overdose. High salt consumption pushes up blood pressure, which in the long term can lead to strokes and heart attacks. These are the country’s biggest causes of death and disability.

Health campaigners took two typical daily menus enjoyed by many children and calculated the salt content to be 9.3g to 9.6g. However, for a child aged seven to ten, the recommended maximum is just 5g. Eating 9.6g of salt in a day would be 92 per cent above this amount – nearly double.

The menu which contained this much salt started with a bowl of cereal for breakfast, followed by a muffin for a mid-morning snack. Lunch included a ham and cheese sandwich, a pack of crisps, cheese dip snack and a biscuit, which had a combined salt content of 3.7g. Dinner included potato croquettes, chicken nuggets, baked beans and ketchup

Safe daily amounts of salt vary depending on age and size, starting at 1g or less for babies. If the entire nation cut down to these levels, doctors estimate that 70,000 heart attacks and strokes would be prevented in just one year.

Consensus Action on Salt and Health has been campaigning for food manufacturers and supermarkets to remove hidden salt. Campaign director Katharine Jenner said: ‘Popular foods like bread, cereal, baked beans, cheese, tomato sauce and processed meats are some of the biggest culprits. So try not to feed your child them every day. ‘Also, throw away the salt cellar. If you eat food which tastes less salty, your taste buds adapt really quickly.’

She warned: ‘The higher the blood pressure in childhood, the higher the blood pressure will be in adulthood. ‘By getting your child used to less salt, you are protecting their health in the long term.’

Health Secretary Andrew Lansley has set up a voluntary scheme, the Responsibility Deal, to encourage firms to meet salt reduction targets. The major supermarkets and leading brands such as Heinz, Kellogg’s, Subway and Mars have signed up.

Miss Jenner said: ‘It is in their best interests if they want to prolong the lives of their customers.'


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