Chemotalk Newsletter, Vol. 23: March 1, 2010
MORE DOSES OF MS DRUG RAISE RISK OF BRAIN INFECTION
In the latest blow to the controversial multiple sclerosis drug Tysabri, the U.S. Food and Drug Administration on Friday announced that it was slapping a new warning on the drug's label.
In an advisory sent to health-care professionals and patients, the FDA warned that the risk of developing progressive multifocal leukoencephalopathy (PML), a rare but deadly brain infection, increases as more infusions are received. "This is updated information, taking new cases into account," explained Dr. William Sheremata, professor emeritus of neurology at the University of Miami Miller School of Medicine, who first gave the drug to humans. European patients account for most of the new cases and many of them might have been taking multiple drugs, raising their risk for PML, he added.
"This is not new information. We've had this information for a couple of months now [but] the labeling in the past did not make a distinction between the time frames that people were on the drugs," said Dr. John Richert, executive vice president for research and clinical programs at the National Multiple Sclerosis Society. "The risk-benefit ratio continues to be about the same as we anticipated since the time the drug was brought back on the market."
Another expert agreed that the clinical picture hasn't been altered by the new label warning. "I think as long as the medication is being prescribed for the appropriate patient with MS, then the new information we have today is not going to alter medication management," said Dr. Jeffrey Tramonte, director of neurology at the Scott & White University Medical Campus in Round Rock, Texas. "Right now, Tysabri is the most efficacious drug that's ever been approved for the treatment of RELAPSING-REMITTING MS, which represents 85% of all patients out there who have MS," he said. "However, it also carries the single most dangerous risk factor, and that's PML," added Tramonte, who only gives Tysabri if his patients have failed or have severe side effects from conventional immunomodulating drugs.
Natalizumab (Tysabri) first received FDA approval in November 2004, only to be pulled from the market three months later after several patients in clinical trials developed PML. In June 2006, the FDA allowed the drug back on the market, but with strict conditions. According to those revised guidelines, Tysabri can only be administered by approved doctors, at infusion sites and at pharmacies that register and comply with a patient-safety program called CD Touch, designed by drugmaker Biogen Idec and approved by the FDA. The FDA said the new action was based on reports of 31 confirmed cases of PML as of Jan. 21, 2010.
Information on the risk will also be included in the patient Medication Guide. However, the FDA did not suggest discontinuing the drug, stating that it "believes that the clinical benefits of Tysabri continue to outweigh the potential risks." The drug was approved to treat Crohn's disease in early 2008. It is also linked with liver damage. Patients do take the drug long-term, Richert said.
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LUNG CANCER DRUG ZAPS TUMOR BLOOD VESSELS
Study Finds Vadimezan Plus Chemo Prolongs Survival in Lung Cancer Patients
A new lung cancer drug that disrupts blood vessels within the tumor and inhibits blood flow to it looks promising, say researchers. When added to traditional chemotherapy, the new drug, called vadimezan and also known as ASA404 or DMXAA, extended survival time, says Mark McKeage, PhD, an associate professor in clinical pharmacology at the University of Auckland, New Zealand, who presented the findings at the American Association for Cancer Research -- International Association for the Study of Lung Cancer meeting.
"Overall survival was improved numerically from a median of 8.8 to 14 months (half lived longer, half less). The safety profile is favorable."
In the phase II study, McKeage and his colleagues evaluated 108 patients who had advanced (stage IIIb or IV) NON-SMALL-CELL LUNG CANCER, the most common type of lung cancer. They assessed 104 of them for the safety evaluation and 100 to compare survival differences. Non-small-cell lung cancer is further divided into squamous cell carcinoma (cancer that originates from squamous cells, which are cells that line the airways) and non-squamous cell carcinoma, which includes other cell types. Patients received either standard chemotherapy or chemo plus the new drug. Two different doses of the new drug were tried, McKeage says.
Lung Cancer Drug: Study Results
Giving patients the drug in addition to chemo didn't increase the toxicity of the chemo, McKeage found, and survival was greater with the combined approach at either dose. When he looked at those with squamous cancers, survival was 10.2 months in those who got the drug plus the chemo, compared with 5.5 months in those who received chemo alone. For patients with non-squamous cancers, survival was 14.9 months with the combination therapy but 11 months on chemo alone.
"The range in survival is from a few weeks up to over a year, 18 months," he says. "One of these people is still alive, disease free, over four years after treatment. This patient had a fantastic response and then went [on] and had surgery [for the cancer]."
The most commonly reported side effects were blood and lymphatic disorders, reported by about 18%, but no serious adverse events were reported with lung hemorrhage or bleeding, a side effect that has accompanied other lung cancer drug therapy, McKeage says. The improvement is encouraging and warrants further investigation by proceeding to the phase III trial.
McKeage was the principal investigator for the study, which was funded by Antisoma, who later licensed the drug to Novartis Pharmaceuticals Corp. McKeage has consulted for both companies and received research funds from both.
Vadimezan works in a different way than another cancer drug that focuses on blood vessels, Avastin, McKeage says. They compare favorably, but vadimezan has fewer side effects.
Recruitment for the phase III study is complete, he says. He predicts the new drug may be on the market by 2012 or so.
"One of the important points of this analysis is that it shows the efficacy and safety profile [of the drug] was similar in squamous and non-squamous patients," McKeage says.
Lung Cancer Drug: Second Opinion
The results of the vadimezan study represent "a considerable improvement in survival," says Paul A. Bunn Jr., MD, professor of medicine, James Dudley Chair in Cancer Research at the University of Colorado, Denver, and executive director of the International Association for the Study of Lung Cancer. "Almost every year now, we are getting [new] drugs that improve survival in lung cancer patients." However, he adds, "we have a long way to go."
In the U.S., about 219,000 new cases of lung cancer were expected to be diagnosed in 2009, with 159,000 expected deaths from the disease, according to American Cancer Society estimates. Survival rates depend on the stage, with the five-year survival rate for stage IV non-small-cell lung cancer just 1%, according to the society.
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'GHOSTLY' DRUG MAY HELP FIGHT RA'Ghostly' Study Shows Molecule Can Infiltrate Immune Cells to Treat Rheumatoid Arthritis
A ghostly "suicide" drug wafts into immune cells in joints, making the cells self-destruct and reducing rheumatoid arthritis in mice.
The drug, technically a BH3 mimetic dubbed TAT-BH3, is a man-made molecule. One part of the molecule lets it drift through cell walls. The other part mimics a chemical signal missing in the macrophage immune cells that build up inside joints afflicted by RHEUMATOID ARTHRITIS.
Because they are missing this signal, macrophages in RA joints don't die off as they are supposed to do. They live on, destroying bone and inflaming the joint, says Harris Perlman, PhD, associate professor of medicine at Chicago's Northwestern University Feinberg School of Medicine. "In RA, there is this persistent inflammation that never shuts down. Part of the reason is these macrophages are missing a protein they need to die off. So this drug says OK, let's replace this protein. Let's bring back the death pathway," says Perlman.
Perhaps because normal cells aren't clinging to life like the zombie macrophages involved in RA, the drug doesn't kill normal macrophages. The drug was not toxic to mice. But in mice with RA, injections of TAT-BH3 cut bone erosion by as much as 39% and thinned the too-thick lining of the joint by up to 34%.
Perlman says that by hitting it's Bim-protein target, TAT-BH3 has therapeutic effects that go beyond just killing macrophages. "This drug does far more than cause cell death," he says. "We think this Bim protein has multiple functions and may be a great target for disease."
Perlman's team and others are making their molecule more appropriate for human treatment. One approach they are trying is to use tiny nanoparticles to speed the BH3 mimetic through cell walls. Much work remains before their drug prototype is ready for human studies.
Other BH3 mimetics, with targets different from the so-called Bim protein that is the focus of the Perlman study, are being developed as cancer treatments. Some already are showing promising results in clinical trials.
The Perlman study appeared in an issue of Arthritis & Rheumatism.
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With the healthcare universe as difficult to navigate as it is today, fighting claims that are denied are becoming more and more important. This article from The New York Times provides the best step-by-step program for patients to fight denied claims, that I've seen so far. If you toss this newsletter after reading it, make a copy of this article first:
FIGHTING DENIED CLAIMS REQUIRES PERSEVERANCE*
MARIA CARR, a 43-year-old school administrator from Tulare, Calif., could not believe it when her insurer, UnitedHealth, denied coverage for arthroscopic surgery she underwent last year to treat a bone spur on her hip.
Her doctor told Ms. Carr he had successfully performed this procedure for eight other UnitedHealth patients suffering from the same ailment in the same year. To Ms. Carr¹s mind, arthroscopy seemed a much less invasive and cheaper way to treat the problem than open hip surgery, the traditional treatment for bone spurs. ³When the denial came I was shocked,²
Ms. Carr said, ³but I figured I¹d just have to find a way to pay.² The total bill for the hospital and surgeon fee was $21,225. Ms. Carr¹s form of shock is all too common. The Department of Labor estimates that each year about 1.4 billion claims are filed with the employer-based health plans the department oversees. Of those, according to data collected from health insurance industry sources, 100 million are initially denied. In simpler numbers, that is one of every 14 claims.
But Ms. Carr, whose hip pain ceased after the arthroscopic surgery, did not give up on the reimbursement. And neither should you. When Ms. Carr, a special education administrator at a local charter school, read her explanation of benefits statement more carefully, she spotted some instructions on how patients can appeal denied claims. ³
I decided I would fight,² she said. ³After all, what did I have to lose?²
Ms. Carr researched medical journals and other publications to find proof that her procedure was a bona fide and safe treatment. She then wrote a formal letter to her insurer making her case and including copies of the research she had found. Her doctor backed her up with a thorough letter of his own.
The appeal was initially denied, but Ms. Carr kept fighting. She took her case to her insurer¹s external review board, where an impartial medical expert weighed the evidence. The expert agreed with Ms. Carr, saying UnitedHealth had to pay the claim. ³The expert felt UnitedHealth couldn¹t call the procedure experimental if it paid for other patients to have it,² Ms. Carr said. UnitedHealth ended up paying $12,282 for Ms. Carr¹s claim ‹ at a rate the insurer negotiated with the doctor and hospital. Ms. Carr¹s share was about $500. ³
That¹s what the appeals process is there for,² said Cheryl Randolph, a spokeswoman for the insurer. ³We¹re glad it worked for her, and we encourage members to exercise their right to appeal whenever they need to.²
Not that UnitedHealth now happily pays all such claims. Soon after Ms. Carr¹s successful appeal, the insurer revised its policy to stipulate that it did not cover that type of hip procedure ‹ although Ms. Randolph says the company is now rethinking things once again because of "the changing landscape of medical literature" about the procedure.
Whatever the treatment or procedure a patient receives or is contemplating, a variety of things can prompt a claims denial. It might be a simple clerical error, like an incorrect address, or a doctor¹s use of the wrong diagnostic or treatment code for your treatment.
Then there are the more serious causes ‹ as when a treatment is specifically excluded from your policy, for example, or, as in Ms. Carr¹s case, when the insurer deems a procedure experimental and therefore ineligible for reimbursement. Other frequently denied claims involve emergency room visits, especially those at out-of-network hospitals and clinics.
Another big category involves chronically ill patients, who often must try several medicines and treatments to find the one that works best for them. Such patients can become all too familiar with insurance denials, says Jennifer C. Jaff, founder of Advocacy for Patients with Chronic Illness.
But as Ms. Carr discovered, if you are denied coverage you have a right to appeal. And in most cases, experts advise you to do just that. Approximately half of all appeals are successful, according to anecdotal evidence from patient advocacy groups and data from individual states. ³
About 53 percent of appeals work in our state,² said the Kansas insurance commissioner, Sandy Praeger. ³That demonstrates that the process works.²
Use the following advice to increase your chances of success in appealing a health insurance denial. As you¹ll see below, expert help may be available. And if you feel in over your head, and a significant amount of money at stake, it may even be worth hiring a type of specialist known as a "billing advocate".
READ YOUR POLICY Always check your policy carefully before you undergo treatment. Many denials are made because the policy specifically excludes coverage of a certain treatment, procedure or medicine, Ms. Praeger said. When it is spelled out that something specific is not covered, an appeal will not work.
TAKE YOUR TIME When you decide to appeal, do not act in haste, advises Ms. Jaff, of the patient advocacy group. Most insurers allow a certain amount of time for an appeal, usually 60, 90, or 180 days. If you call and say I want to appeal, the insurer may consider that the appeal, itself. So you want to take advantage of the time you have (without missing the deadline) to build your case.
Before you file, make sure you have all the information you need from your insurer to start your appeal in earnest. Your explanation of benefits should provide a code for the reason for the denial, and that code should be translated somewhere on the statement. If it is not, or if you still have questions, contact your insurer.
Make it clear in your phone call or letter that you are not officially starting the appeal process. You simply have questions. If it is not already clear, you should also ask exactly to whom the appeal should be sent. (You do not want precious time wasted because your appeal was shuffled from desk to desk.)
Whenever you call your insurer, be sure to make a note of the time and date and the person you talked to. If you send a letter, send it registered mail with return receipt, and keep your own copy.
DO RESEARCH Once you learn why your claim was denied, customize your appeal to argue specifically against that reason. A clerical or coding error is fairly straightforward, but just to be sure, enlist the help of your doctor¹s or hospital¹s billing specialist to back you up with a letter explaining how the mistake was made.
Something more complicated, like an out-of-network emergency claim, will require proof that the situation was indeed a medical emergency and that no in-network provider was available. Obtaining your medical records can help support your argument, so can letters from the doctors who treated you.
Fighting a denial for something your insurer deems experimental can be the trickiest appeal. In addition to support from your doctor, you will need to find articles from established medical journals for evidence that the treatment is not only effective but safe.
You can find abstracts of many articles free on pubmed.gov, the library of the National Institutes of Health. Often the abstracts are enough to make your point. If you need the full article, which can be expensive, ask your doctor¹s office for help or check with a local medical school library. Any proof you can show that other insurers in your area cover the treatments in question can be valuable. Most big insurers list medical policies concerning treatments on their Web sites. Your doctor¹s office can probably help with this, too. You also must prove the medical necessity of a treatment, especially if it is considered experimental. Ms. Jaff, for instance, learned this when she was denied coverage for a certain drug her doctor prescribed for Crohn¹s disease. Her insurer argued that other, more established drugs could treat the problem. True enough, but Ms. Jaff had already tried those drugs without success. For her appeal, Ms. Jaff collected her medical records that showed when she had tried each drug and how each had failed. The strategy worked, and her claim was ultimately paid.
Be sure to stick to the facts in any argument you make. Emotional or angry arguments, as much as they may feel warranted, will not help your case, said Erin Moaratty, who heads special projects for a group called the Patient Advocate Foundation.
GO THE DISTANCE Even if your well-researched and thorough appeal is denied, do not give up. You still have options, depending on the type of insurance you have.
If you receive coverage directly from an insurance company, say through a private policy or from your small or midsize employer, your insurer is regulated by your state¹s insurance department. All but five states, Alabama, Mississippi, Nebraska, South Dakota and Wyoming, allow patients to have their appeals considered by an independent external review board, usually after all internal appeals have been exhausted.
In most cases the board consists of doctors and other professionals with an expertise in your condition. For more information on your state¹s rules contact its department of insurance. To find yours, go to the National Insurance Commission¹s Web site and click on your state.
Large employers that self-insure ‹ meaning that they pay medical claims themselves, not through an insurance company ‹ are not subject to state insurance laws. But most have provisions for external appeal reviews. Check your plan summary, the large booklet you received when you signed up for health care, for details.
GET HELP Your state insurance department can help answer questions and start an appeal. In addition, groups such as Advocacy for Patients with Chronic Illness and the Patient Advocate Foundation help seriously ill patients file appeals free.
Be sure to check the advocacy organizations for the illness you have. Many offer free advice on dealing with health insurance disputes with specific information related to your condition.
You may also want to seek help from a medical billing advocate (see our earlier column ³A Guide through the Medical Wilderness²). Depending on the case, these professionals charge an hourly fee or a percentage of any recovered claim.
* Successfully fighting pet insurance claims are just as good an idea. When my pet insurance company called my dog's back injury a "pre-existing condition", I took them to court, with my dog's surgeon for a witness. The insurance company not only had to pay the $6,700 cost of the operation and treatment, but the interest on the bill, as well.
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More from The New York Times:
LIVING WITH A FORMERLY FATAL BLOOD CANCER
By Jane E. Brody
In December 2005, a series of mysterious symptoms - night sweats, easy bruising, swollen ankles and breathlessness upon exertion - prompted Barry to see his doctor. Only six months earlier, a physical exam had found nothing abnormal. But now Barry's white blood cell count was through the roof.
A bone marrow test the next day revealed a genetic abnormality called the Philadelphia chromosome that is the signature of chronic myelogenous leukemia, or C.M.L., a blood cell cancer that in the last decade has been transformed from ultimately fatal to nearly always treatable, usually until something else claims the patient's life.
Despite his illness, Barry, a lawyer who for privacy reasons asked that his last name not be used, is living a normal life. "I go to the gym, go to work, travel, play with my grandson - that's the best," he said in an interview. In some of my support groups, people have been living with the disease now for 10 or 12 years."
Before 2000, fewer than half of C.M. L. patients survived seven years; now nearly 90 percent are alive seven years after diagnosis and, like Barry, lead relatively normal lives. (The basketball start Kareem Abdul-Jabbar announced in November that he had been living with the disease for nearly a year.)
"C.M.L. Has become a chronic disease leading to a normal life span in the majority of patients," Dr. Elias Jabbour of the University of Texas M. D. Anderson Cancer Center said in a teleconference workshop sponsored by CancerCare. "As for quality of life, among more than 3,000 patients who have been followed now for almost 10 years, there's been no significant increase in the incidence of infection, other cancers, or other causes of death when compared to the normal population."
What led to this turnaround was identification of the genetic marker of the disease and development of a drug called Gleevec (imatinib), which attacks the leukemia-promoting protein, tyrosine kinase, found in 95 percent of C.M.L. Patients
Since the approval in 2001 of Gleevec, a drug that inhibits activity of this protein, two other even more powerful tyrosine kinase inhibitors have been approved by the Food and Drug Administration to treat the disease.
Barry, for example, is now on the third generation of anti-C.M.L. Drugs, Tasigna (nilotinib), after his cancer became resistant to control by Gleevec and he developed an uncontrollable side effect to its successor, Sprycel (dasatinib).
A Model of Complexity
But while the success to date with C.M. L. has been nothing short of inspirational, the experience over the past decade with this genetically relatively simple cancer has demonstrate why it is so challenging to find cures for other cancers, most of which are much more complex.
As sometimes happens with C.M.L., all it takes for a cancer to escape the stranglehold of modern therapies is for one cancer cell to develop a treatment-resistant mutation and take over.
"C.M.L. Is a disease we always considered to be a model of genetic abnormality," Dr. Jorge E. Cortes, a leukemia specialist at M. D. Anderson, said in an interview. "All one needed to do is design a drug directed at that abnormality and get a great response. Then we started to uncover just how heterogeneous this 'homogeneous' disease really is.
"The expression of certain genes is very different in different patients. While the majority of patients respond well to Gleevec, some don't, some respond initially and then lost the response, and some develop mutations that may or may not be sensitive to the drugs."
` Among patients who develop resistance to the treatments, Dr. Cortes said, "only about half have a mutation that we can detect."
"And in those with a mutation," he continued, "the presence of mutated cells seemed to affect the nonmutated cells and make them more resistant to treatment. Even in a disease that is genetically simple, these leukemic cells don't just roll over and die, even if attacked by very effective weapons. They find ways to survive."
In the M.D. Anderson publication Onco-Log last June, Dr. Cortes said: "We've clearly changed the natural history of this disease with imatinib, but it doesn't work for everybody. We still need to improve therapy, in both newly diagnosed an resistant disease."
Another problem is an inability to know for certain if and when the disease has been cured. For as long as a drug is working, patients must now continue to take it every day to keep the disease suppressed. And the cost is astronomical -- $98,000 a year, Barry said. He is now on Medicare, and in just one month he reached the "doughnut hole" in the program's rug benefit, during which he must pay the full cost of treatment before the insurance resumes.
Still, Barry remains very encouraged. As he learned fro the latest conference of the American Society of Hematology, "they're working on vaccines and drug combinations, as well as additional drugs for C. M. L., to address a mutation that current drugs don't handle."
Stages of the Disease
C. M. L. was diagnosed in about 5,050 new patients last year in the United States, most of them, like Barry, in midlife or older. And, like Barry, about 95 percent of patients have the distinctive Philadelphia chromosome in their leukemic cells. Those missing this genetic trait have a poorer response to treatment.
The Philadelphia chromosome results from a gene exchange between chromosomes 9 and 22. The resulting new "fusion" gene, called Bcr-Abl, dictates the production of the leukemia-promoting enzyme, tyrosine kinase.
The disease, however, is not inherited. The only known risk factor is exposure to high doses of ionizing radiation, like what occurred in the bombings of Hiroshima and Nagasaki. The disease occasionally occurs in patients who were heavily treated with radiation for previous cancers.
C. M. L. has three stages: chronic, accelerated and blastic. At diagnosis, Barry, like 85 percent of new patients, was in the chronic phase, the earliest and easiest stage to control. There are relatively few abnormal "blast" cells in the blood and bone marrow. Some patients at this stage have no symptoms or only mild vague ones like fatigue and a feeling of abdominal fullness, and they learn of their disease through a routine blood test.
In the accelerated phase, which develops over years and signals imminent progression to uncontrollable disease, symptoms are prominent and blast cell numbers in the blood and bone marrow are higher. Once patients develop the final phase, a blast crisis, the spleen can become dangerously enlarged and the disease, which more closely resembles acute leukemia, progresses rapidly.
Dr. Cortes cautioned patients against stopping therapy when they appeared to be perfectly healthy. Those who fail to stick with continuous daily treatment are ore likely to relapse.
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BLOOD TEST MAY PREDICT RHEUMATOID ARTHRITIS Proteins in Blood May Signal RA Years Before Symptoms Develop
Elevated levels of inflammatory proteins called cytokines and related factors in the blood may be an early warning sign of impending rheumatoid arthritis (RA), according to a new study.
Researchers have found that levels of certain cytokines and related factors in the blood increase significantly prior to the development of rheumatoid arthritis, long before symptoms emerge. They say the finding paves the way for developing a blood test for early diagnosis of the mysterious disease.
"Our findings present an opportunity for better predicting the risk of developing RA and possibly preventing disease progression," says researcher Solbritt Rantapää-Dahlqvist, MD, of University Hospital in Umea, Sweden, in a news release.
Rheumatoid arthritis can be difficult to diagnose in the early stages because it often begins with only subtle symptoms, such as achy joints or early morning stiffness. Other conditions, such as lupus, osteoarthritis, and fibromyalgia may also mimic the early symptoms of rheumatoid arthritis, which makes a definitive diagnosis difficult. But studies have shown that early diagnosis and treatment of rheumatoid arthritis can help sufferers live a more active life and potentially avoid the type of joint damage that leads to disability.
Early Signs of RA
The cause of rheumatoid arthritis is not understood, but various components of the immune system and synovial tissue, which lubricates the joints, are thought to be involved. Cytokines are pro-inflammatory proteins that are often found in the synovial tissue after rheumatoid arthritis has developed.
In the study, published in Arthritis & Rheumatism, researchers examined whether particular cytokines and related factors are elevated prior to the emergence of rheumatoid arthritis symptoms. They analyzed blood samples from 86 people in Sweden without symptoms of rheumatoid arthritis at the time of donation who later developed RA and compared them with samples from 256 healthy individuals. The results showed levels of several cytokines and related factors were elevated up to years before diagnosis with rheumatoid arthritis.
Researchers say the findings support the idea that the immune system was already stimulated and rheumatoid arthritis was developing. If further studies confirm these results, a blood test to screen for these elevated cytokines may help diagnose RA before symptoms emerge.
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Finally, if you don't live in California, you probably haven't noticed how the forces against medical marijuana have been chipping away at the voters' initiative that made it available for medical reasons. Using any self-righteous argument they can invent, and preying on the fears of those who don't know anything about marijuana except for recreational use, they are pushing an agenda to show they're "tough on crime". One example of the politically-motivated tug-of-war is being played out between the Los Angeles City Attorney's war on marijuana, and the City of West Hollywood's refusal to limit access. Behind the drama is the DEA, determined as ever to re-criminalize marijuana, as evidenced in the following article from The New York Times:
RESEARCHERS FIND STUDY OF MEDICAL MARIJUANA DISCOURAGED
By Gardiner Harris
Despite the Obama administration's tacit support of more liberal state medical marijuana laws, the federal government still discourages research into the medicinal uses of smoked marijuana. That may be one reason that - even though some patients swear by it - there is no good scientific evidence that legalizing marijuana's use provides any benefits over current therapies.
Lyle E. Craker, a professor of plant sciences at the University of Massachusetts, has been trying to get permission from federal authorities for nearly nine years to grow a supply of the plant that he could study and provide to researchers for clinical trials.
But the Drug Enforcement Agency - more concerned about abuse than potential benefits - has refused, even after the agency's own administrative law judge ruled in 2007 that Dr. Craker's application should be approved, and even after Attorney General Eric H. Holder Jr. in March ended the Bush administration's policy of raiding dispensers of medical marijuana that comply with state laws.
"All I want to be able to do is grow it so that it can be tested," Dr. Craker said in comments echoed by other researchers.
Marijuana is the only maJor drug for which the federal government controls the only legal research supply and for which the government requires a special scientific review.
`"The more it becomes clear to people that the federal government is blocking these studies, the more people are willing to defect by using politics instead of science to legalize medicinal uses at the state level," said Rick Doblin, executive director of a nonprofit group dedicated to researching phychedelics for medical uses.
On Monday, his last full ay in office, Gov. Jon S. Corzine of New Jersey signed a measure passed by the Legislature last week that made the state the 14th in the nation to legalize the use of marijuana to help with chronic illnesses.
The measure was pushed by a loose coalition of patients suffering from chronic illnesses like Lou Gehrig's disease and MULTIPLE SCLEROSIS who said marijuana eased their symptoms.
Studies have shown convincingly that marijuana can relieve nausea and improve appetite among CANCER patients undergoing chemotherapy. Studies also prove that marijuana can alleviate the aching and numbness that patients with H.I.V. an AIDS suffer.
There are strong hints that marijuana may ameliorate some of the neurological problems associated with such degenerative diseases as multiple sclerosis, said Dr. Igor Grant, director of the Center of Medicinal Cannabis Research at the University of California, San Diego.
But there is no good evidence that legalizing the smoking of marijuana is need3ed to provide these effects. The Food and Drug Administration in 1985 approved Marinol, a prescription pill of marijuana's active ingredient, T.H.C. Although a few small-scale studies done decades ago suggest that smoked marijuana may prove effective when Marinol does not, no conclusive research has confirmed this finding.
And Marinol is no panacea. There are at least three medicines that in most patients provide better relief from nausea and vomiting than Marinol, studies show.
Buddy Coolen, 31, of Warwick, R.I., said he tried or continued to use some of those medicines. "Smoking for me is as good as any medicine I have," he said.
Eight years ago, Mr. Coolen contracted gastroparesis and cyclic vomiting syndrome. He lost 50 pounds and, despite being 5 foot 11, weighed 120 pounds.
His doctors gave him myriad anti-emetics, many of which he still takes. They also prescribed Marinol, but it did not work for him, Mr. Coolen said.
"My stepdad is old school and was really against marijuana, but then he saw what it did for me and totally changed his way of thinking," Mr. Coolen said.
Some doctors and law enforcement officials say such anecdotes should not drive public policy. Dr. Eric Braverman, medical director of a multispecialty clinic in Manhattan, said legalizing marijuana was unnecessary and dangerous since Marinol provided the medicinal effects of the plant. "Our society will deteriorate," he said.
Patients who call Dr. Braverman's clinic are, when pu on hold, told that the clinic may prescribe supplements and other alternative treatments that have even less scientific justification than marijuana. Dr. Braverman said such alternatives rendered marijuana unnecessary, but his embrace of alternatives is a reminder that medicine has long been driven by more than science.
About 20 percent of drug prescriptions are written for uses that are not approved by federal drug regulations, an half of the nation's adults regularly take supplements; herbal and homeopathic remedies are popular.
The nation's growing embrace of medical marijuana has stemmed from these alternative traditions.
The University of Mississippi has the nation's only federally approved marijuana plantation. If they wish to investigate marijuana, researchers must apply to the National Institute on Drug Abuse to use the Mississippi marijuana and must get approvals from a special Public Health Service panel, the Drug Enforcement Agency and the Food and Drug Administration.
But federal officials have repeatedly failed to act on marijuana research requests in a timely manner or have denied them, according to a 2007 ruling by an administrative law judge at the Drug Enforcement Agency. While refusing to approve a second marijuana producer, the government allowed the University of Mississippi to supply Mallinckrodt, a drug maker, with enough marijuana to eventually produce a generic version of Marinol.
"As the National Institute on Drug Abuse, our focus is primarily on the negative consequences of marijuana use," said Shirley Simson, a spokeswoman for the drug abuse institute, known as NIDA. "We generally do not fun research focused on the potential beneficial medical effects of marijuana."
The Drug Enforcement Agency said it was just following NIDA's lead. "D.E.A. has never denied a research registration for marijuana and/or THC if NIDA approved the protocols for that individual entity," a supervisory special agent, Gary Boggs, said in an e-mailed statement.
Researchers investigating LSD, Ecstacy and other illegal drugs can use any of a number of suppliers licensed by the Drug Enforcement Agency, Dr. Doblin said. And I a researcher wants to use a variety of marijuana that the University of Mississippi does not grow - and there are many with differing medicinal properties - they are out of luck, Dr. Doblin said.
Law enforcement tends to emphasize and abuse potential of medicines without regard to their positive effects. Bureaucratic battles between the D.E.A. and the F.D.A. over the availability of narcotics - highly effective but addictive medicines - have gone on for decades.
So medical marijuana may never have good science underlying its use. But for patients in desperate need, the ethics of providing access to the drug are clear, said Dr. Richard Payne, a professor of medicine and divinity and director of the Institute for Care on the End of Life at Duke Divinity School.
"It's not a great drug," he said, "but what's the harm?"
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More next month...
And if you have any thoughts of how this newsletter could be improved, please email me directly, at firstname.lastname@example.org