Burgess hopes to block FDA from regulating genetic tests

[barbara]

Surely, there must be a happy medium between the FDA's proposed regulation which is burdensome to the continual changes taking place in this field and one of no regulation where every Tom, Dick and Harry can slap up a shingle and claim to be doing genetic testing.


Healthwatch
By Sam Baker 11/17/11

Letting the Food and Drug Administration regulate genetic tests would cripple innovation in a field with tremendous promise for patients and U.S. competitiveness, Rep. Michael Burgess (R-Texas) said Thursday.

The FDA has said it intends to regulate genetic tests that are developed in laboratories. Burgess, who is a doctor, has introduced a bill to block the FDA’s effort. The drug and device industries complain about long approval delays at the FDA, and Burgess said he’s afraid genetic tests would be “subsumed” by that bureaucracy.

“We need a regulatory framework that is sensitive to the fact that this is an evolving science,” Burgess said Wednesday at a policy forum sponsored by The Hill and the American Clinical Laboratory Association.

Genetic tests have the potential to identify risk factors even before a patient gets sick and to help tailor treatments to each patient’s unique needs. The technology, however, is still relatively new.

“We do lead the world, and this is a resource we can ill afford to lose or regulate out of existence,” Burgess said.

Burgess acknowledged that his bill to stop the FDA from regulating lab-developed tests hasn’t gotten much attention. He said he wants to move it through the regular legislative process, rather than attach it to a separate bill.

Rep. Charles Gonzalez (D-Texas) told an emotional story about a cancer patient who used genetic testing to figure out whether her daughters were also at risk for cancer, saying he agreed fully with the need for further innovation. But also said generally that he and other Democrats might have problems with Burgess’s proposal.

His bill would explicitly state that the FDA doesn’t have the legal power to regulate genetic tests — authority Burgess said he was “concerned” to see the agency exerting without a clear sign-off from Congress.

Marc Grodman, chief executive of Bio-Reference Laboratories, said FDA regulation would unnecessarily stand in the way of important advances.

“Freezing technology, freezing innovation in an industry that is already regulated only has an effect to increase cost,” Grodman said.

The tests are currently regulated under the Centers for Medicare and Medicaid Services (CMS). Moving oversight from CMS to the FDA would make it harder to get the most out of genetic testing, Grodman said.

Genetic tests are often used as a diagnostic tool. And drug companies are developing new, more narrowly targeted products to go hand in hand with the tests. But Grodman said FDA regulation could raise the risk that test developers would have to seek a new approval along with every new drug that puts a slight twist on fundamentally the same test.

“We need the ability to innovate; we need the ability to provide data,” he said.

[barbara]

Genetic Testing for Eye Tumor Cuts Surveillance Costs

By Nancy Walsh, Staff Writer, MedPage Today
Published: November 17, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner


This study indicates that genetic testing can be done promptly and successfully in the majority of family members of children affected with retinoblastoma, a potentially hereditary condition, particularly when bilateral.

The ability to identify children negative for the mutation eliminates the need for screening, a procedure which carries significant cost and potential morbidity.

Genetic testing of children with retinoblastoma and their families greatly reduced unnecessary and expensive clinical surveillance among potentially at-risk family members, a study suggested.

Analysis of the RB1 gene among 48 family members of affected children identified six individuals who carried a mutation predisposing them to retinoblastoma, although they were clinically unaffected.

This meant that 42 were negative for the mutation and did not need repeated evaluations, according to Sharon E. Plon, MD, PhD, of Texas Children's Cancer Center in Houston, and colleagues.

"If genetic testing had not been performed, these 42 individuals would have had to undergo expensive [examinations under anesthesia] as part of surveillance recommendations," the researchers wrote in the November Archives of Ophthalmology.

Retinoblastoma is an unusual malignant ocular tumor of early childhood that can affect one or both eyes.

In the 40% of cases that are bilateral, a germline mutation in RB1 is responsible; the remaining 60% of cases, which present as unilateral, have either a somatic mutation in the gene -- one that occurs during development -- or, in about 15% of unilateral patients, a hereditary mutation.

Retinoblastoma can occur if there are two mutations in RB1 or a single mutation plus inactivation of a second allele.

Testing for the genetic mutation has been available and growing increasingly sensitive during the past 15 years, with the goal of determining risk for additional cancers among affected children and for the ocular tumor itself in family members.

The importance of being able to determine these risks as early as possible lies in the fact that prognosis in retinoblastoma is "highly dependent on prompt diagnosis and evaluation," the researchers observed.

Guidelines on surveillance for those at risk have been developed, but little is known about the implementation of recommendations in clinical practice, so Plon and colleagues reviewed the charts of 90 children evaluated at Texas Children's Hospital between 2001 and 2008.

The management process used by Plon's team involved molecular analysis of blood and/or tumor tissue, and a multidisciplinary program of monthly meetings with geneticists, genetic counselors, pediatric neuro-oncologists, and pediatric ophthalmologists in which each case was discussed and updated.

These meetings also ensured that all cases were referred for genetic testing and the results disseminated to parents and other family members.

In 42% of the children in this series, tumors were present in both eyes.

Genetic testing was completed in 65% of children with bilateral tumors and in 62% of those with unilateral disease.

For bilateral disease or in cases where there is a family history of retinoblastoma, the testing can be done on samples of blood, but in unilateral cases, analysis of the tumor DNA is needed following removal of the eye.

During the early years of the study, the laboratory analysis included only DNA sequencing, which provided a mutation yield of 79%.

After 2004, however, the researchers also were able to obtain copy number analysis and determination of whether promoter methylation was present leading to inactivation of the gene, which improved the yield to 88%.

Among the 29 unilateral cases, a mutation was identified in blood in five, indicating that it was a germline mutation.

In seven of the unilateral cases, no mutations could be detected in blood but they were present in the tumor tissue, signifying sporadic mutations.

The six individuals who had RB1 mutations but no clinical disease were likely to have mutations with limited penetrance or expression, the researchers explained.

Genetic testing was not done in 37% of cases, most often because patients did not return for the appointment.

Other reasons cited for failure to complete testing were cost of the program and the deaths of four patients, which highlighted the importance of the genetic analysis being done as soon as possible after the diagnosis, according to Plon and colleagues.

As to the costs of their program, they noted that the price tag for DNA sequencing was $1,800 for the affected individual and $340 for family members.

But the cost of each evaluation under anesthesia and related fees reached about $3,000, and a child at risk generally needs eight such evaluations in the first year of life and up to 26 by age 6.

"Thus, the relatively inexpensive, simplified familial mutation testing allows a substantial decrease in the expensive and potentially morbid [evaluation under anesthesia] procedures," the researchers noted.

The multidisciplinary approach ensured that evaluations of all at-risk individuals were done promptly, when survival and preservation of vision were most likely to be achieved, they noted.

The authors had no financial disclosures to report.

Primary source: Archives of Ophthalmology
Source reference:
Plon S, et al "Outcomes of integrating genetics in management of patients with retinoblastoma" Arch Ophthalmol 2011; 129: 1428-1434.

[barbara]

And yet another -

by Ken Alltucker - Nov. 19, 2011
The Arizona Republic

It's a scene that could play out anywhere: four 20-somethings laughing, munching on pizza and chatting about plans to go dancing in Scottsdale.

But this group of young men and women at a Phoenix hospital last weekend were far from carefree. They know they each may possess a genetic ticking time bomb that has robbed generations of family members in their homeland of Medellin, Colombia.

The Colombians arrived in Arizona last weekend to participate in a medical study of their extended family of 5,000 with a genetic predisposition to Alzheimer's disease.


Those who carry the rare inherited genetic mutation are destined to get the mind-robbing disease, most likely beginning in their 40s.

They are part of a bold experiment conducted by Banner Alzheimer's Institute and doctors in Colombia that seeks to find ways to identify and treat people who will develop the disease before the first signs of memory loss.

Arizona scientists anticipate the Colombian experiment will open the door to a large Arizona-based study that seeks to halt Alzheimer's disease in its earliest stages. The U.S. study will target adults who carry a certain gene that puts them at risk for Alzheimer's disease and dementia. The study could lead to the possibility of giving disease-scuttling drugs to Americans in their 50s and 60s, before their first memory problems emerge.

But even the most optimistic scientists at Banner Alzheimer's Institute acknowledge a lot of work needs to be completed, and it starts with the Colombians visiting Arizona.

"The progress has been breathtaking," said Dr. Eric Reiman, executive director of Banner Alzheimer's Institute. "We have more work to do, but we are excited about where we are."

So far, three small groups of Colombians have traveled to Banner Good Samaritan Medical Center to undergo PET imaging scans of their brains to measure amyloid plaques, believed to be a hallmark of the disease. A total of 50 Colombians will come to Phoenix for imaging: 20 people under the age of 34, 20 people over the age of 35 and 10 people who already have shown signs of memory or thinking problems.

Researchers expect to gather enough information from these family members to launch a clinical trial in 2013 that will test a plaque-busting drug to determine whether it can halt the progress of the disease. To fund a clinical trial expected to cost $50 million or more, Banner Alzheimer's Institute will seek a federal grant next year. Other funding sources could include the Banner Alzheimer's Foundation and the pharmaceutical industry.

Reiman said that Banner Alzheimer's Institute thought it was important to limit funding from individual companies to avoid the appearance of conflict of interest. Researchers have not decided which drug will be tested, but fewer than one dozen drugs are likely candidates.

Although existing plaque-busting drugs have not proven effective at halting Alzheimer's disease, researchers believe that the drugs have been administered too late, with the disease already ravaging the brain. The Arizona trial will test whether the drugs prove safe and effective if they are given to patients before symptoms emerge.

"We want to release (results) for the entire (Alzheimer's research) field, and we will do that in a very public way," Reiman said. "This will help the field, not just one prevention therapy (drug)."

Several Colombians said they welcome participation in the study because of its promise to help fight a disease that has plagued their extended family for generations.

Adrian Lopez, 24, sat in a Banner Good Samaritan Medical Center room on Nov. 12 after having a PET image of his brain.

"I have hope that the results of the study will help our sons," said Lopez, who works for a financial company in Medellin. "At any moment, I am afraid of this disease. ... If I can help the research, I will feel very good about that."

Scientists already have conducted genetic and memory tests on family members back in Colombia. The family members traveled to Phoenix because the Colombians do not have the positron emission tomography imaging equipment required to track the images of amyloid plaques in the brain.

Of the 40 patients who have shown no symptoms, half carry the genetic mutation that will lead to the disease.

The Colombian scientists who have been tracking the family for two decades decided not to inform individuals about their genetic status, for ethical and practical reasons. Those who know their genetic status likely would require counseling and other support to deal with such devastating news, and the Colombians do not have enough financial resources available.

"In these families, if you have the gene, you will get the disease," said Dr. Adam Fleisher, a Banner Alzheimer's neurologist who is involved in the study. "They do not inform patients of their carrier status. ... Some people do want to (know), but a lot of people don't."

All those who traveled to Phoenix said they see the impact of the disease daily. They have seen and helped care for cousins, aunts, uncles and parents who have been afflicted with memory loss.

Scientists traced the genetic mutation among 25 families all linked to a couple hailing from 18th-century Spain. The disease has long been shrouded in mystery and has been a topic of theories among the people of Antioquia, the region of Colombia that includes Medellin and small villages where many family members live.

A group of four Colombians in their 20s shared smiles and laughter as they discussed their grandparents' theories on how the disease was spread. One common theory was that people could get the disease if they brushed up against a bush. Another belief was that it was some sort of hex from a witch, a curse for perceived transgressions.

Colombian neurologist Dr. Francisco Lopera discovered the common link after treating patients and scouring records of family members afflicted with early-onset dementia. That painstaking research led to the discovery of one malfunctioning gene, a mutation of the PS1 gene, that led to the overproduction of amyloid plaques in carriers.

It is informally referred to as the "paisa" gene, a term used to describe people from their homeland in the northwestern mountainous region of Colombia.

Now that the family members know the science behind the gene, they are eager to join the fight against the disease.

"I am here for a desire to see a cure, to help us fix the disease," said Laura Maria Carmona, 22, whose grandmother, mother and uncles have been affected. "It impacts me directly; I'm hoping for a cure."

Juan David Zapata, 27, said that it is difficult to see healthy family members struck down in the prime of life. His immediate family has escaped the disease, but cousins and uncles have not been spared.

"It's hard," Zapata said. "You think about the way they feel. They are like kids. It's tough to see them live that way."

Colombian doctors who traveled with family members to Phoenix also said it has been a difficult journey.

Sonia Moreno, a neuropsychologist involved in the study, has known the extended family for 17 years. She conducts memory tests and other assessments as part of the study.

"I have seen quite a lot of pain," Moreno said. "I have a good relationship with all the patients. To see them get sick and die, it's hard."

Still, family members share a sense of optimism. Perhaps a new drug or treatment could prove effective -- if not for their generation, then for future generations.

After all, in the past 20 years, the Colombian researchers have discovered the link among the extended family, tracked the disease's path and identified a wayward genetic mutation as culprit. They have cobbled together resources to fly patients to Arizona and test them with the cutting-edge imaging equipment.

Now, in some cases, doctors are working to manage the expectations of the family members.

"It is a big responsibility, because they want a cure," said Natalia Acosta-Baena, a doctor participating in the study.

Acosta-Baena said that she has sought to explain to patients about the long process of testing drugs, that there are frequently failures along the way. Doctors also had to assuage worries among study participants who assumed they carried the disease-causing gene.

"They know this disease is passed from generation to generation," Acosta-Baena said. "It is a matter of balancing hope and faith" and reality.

The Banner Alzheimer's Institute has launched the Alzheimer's Prevention Initiative, an effort to test drugs in clinical trials to prevent or delay the mind-robbing disease. The initiative calls for two prevention studies. One study will include a clinical trial of the Colombian extended family of 5,000 members who carry a genetic mutation that leads to the disease.

A second, U.S.-based trial is planned for people with one or two copies of an Alzheimer's risk gene, called APOE4. The gene is found in about one quarter of the population. It does not guarantee a carrier will develop Alzheimer's, but it increases a carrier's risk of developing the disease.



Read more: http://www.azcentral.com/arizonarepublic/business/articles/2011/11/17/20111117alzheimers-study-links-countries.html#ixzz1eMqLglAH

[LLL6521]

No doubt, as I mentioned several times before, the FDA has become big pharma’s right-hand man to undermine progress to maintain sickness and debilitation for drug sales. They point out some bad apples in the field and justify a new regulation that stalls everyone's research, all in all, out of greed and not for the best interest of the public, like you, me, and everyone else in this forum.