MikeLigalig.com

Recap of Recent FDA Announcements and Decisions
FDA Revises Labels for Erythropoiesis-Stimulating Agents; Sales of Aprotinin Halted; FDA Oversight of Imported Drugs in “Disarray”; FDA Announces Plan To Increase Generic Drugs

The FDA has announced major revisions to the labels of erythropoiesis-stimulating agents (ESAs), anemia drugs indicated for patients with chronic kidney failure or who have cancer and are undergoing chemotherapy. The revisions, which will be applied to epoetin alfa (Procrit, Ortho Biotech; Epogen, Amgen) and darbepoetin alfa (Aranesp, Amgen), reflect evidence of increased risks for serious cardiovascular events in patients treated for chronic kidney failure and evidence of increased tumor growth and shortened survival in patients with cancer.

The anemia drugs have been at the center of a fierce debate between the drugs’ manufacturers, oncologists, the Centers for Medicare & Medicaid Services (CMS) and the FDA. One issue has been reimbursement rates for the drugs; CMS recently issued a final coverage decision that ties reimbursement for ESA initiation to hemoglobin/hematocrit levels of less than 10 g/dL/30%, and limits treatment to eight weeks following chemotherapy.

The second issue has been the safety of ESAs. The revised labels more clearly illustrate evidence that higher target hemoglobin levels lead to increased serious adverse events—including stroke, heart attack and heart failure—in patients with chronic renal failure and tumor growth in cancer patients.

Officials at the FDA emphasized that physicians need to discuss the risks with patients, and will now require that physicians provide patients with a “medication guide” before they receive ESAs.

“FDA strongly recommends that prescribers talk to their patients about the risk that ESAs might cause cancer to grow more quickly or shorten survival before they prescribe these drugs or continue ESA therapy,” said Richard Pazdur, MD, director of FDA’s Office of Oncology Drug Products.

Overall, the new labels reflect evidence from six trials illustrating that higher target hemoglobin levels increase the risk of serious adverse events, including death. All six trials targeted levels between 12 and 14 g/dL.

Because of the complex interaction between ESAs and patients’ hemoglobin response, FDA officials said they were not certain whether target hemoglobin levels or higher ESA doses were more responsible for the adverse outcomes.



Sales of the blood-sparing drug aprotinin have been halted worldwide after regulators in the United States, Canada and Germany asked Bayer to discontinue marketing the medication. Aprotinin (Trasylol) is currently approved to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass during coronary artery bypass graft (CABG) surgery.

The regulatory action follows an analysis of preliminary data from a Canadian study, called BART (Blood conservation using Antifibrinolytics in a Randomized Trial), suggesting that the drug was causing an increased risk of all-cause mortality that had neared conventional statistical significance. The randomized, controlled trial was comparing aprotinin to two other less expensive treatments, the lysine analogs aminocaproic acid and tranexamic acid.

On Oct. 19, 2007, the BART executive committee notified the FDA of its preliminary findings and told officials that they would be halting enrollment in the study. The FDA issued a health alert a week later, but took no other action at that time.

Drug regulators in Germany were the first to suspend sales of aprotinin. The FDA quickly followed suit, issuing a “marketing suspension”—the drug may still be used but will no longer be sold—“based on the serious nature of the outcomes suggested in the preliminary [BART] data.”

“There are not many treatment options for patients at risk for excessive bleeding during cardiac surgery,” the FDA said, so it will phase out aprotinin “in a way that does not cause shortages of other drugs used for this purpose.”

A full withdrawal of aprotinin is pending after a final review of the BART data, officials said. “Until the FDA can review the data from the terminated study, it is not possible to determine and identify a population undergoing cardiac surgery for which the benefits of [aprotinin] outweigh the risks.”

Bayer said it was working with the FDA to develop a program to distribute aprotinin to physicians who might “request and receive [aprotinin] for treatment of certain surgical patients with an established medical need.”

“Bayer believes that the totality of the available data continue to support a favorable risk-benefit profile for [aprotinin] when used according to labeling,” the statement added.



Each year, about $1.4 billion worth of pharmaceutical drugs and drug ingredients are imported into the United States from China and India. A congressional investigation launched by the House Committee on Energy and Commerce has shown that U.S. regulators charged with overseeing foreign drug manufacturers have essentially no basic information about how these companies operate.

About 80% of drug ingredients sold in the United States are manufactured abroad, according to testimony by Rep. Bart Stupak (D-Mich.), chairman of the House Committee on Veterans’ Affairs Subcommittee on Oversight and Investigations.

The investigation was prompted in part by a string of health problems associated with food products originating in China earlier this year.

“More than nine years ago, we reported that the FDA needed to make improvements in its foreign drug inspection program. Yet our preliminary work indicates that fundamental flaws we identified in the management of this program in 1998 persist,” said Marcia Crosse, director of health care for the U.S. Government Accountability Office (GAO), the division of Congress that investigates how well government agencies are performing.

A main finding of the GAO was that the FDA does not have enough information to regulate foreign drug manufacturers. Specifically, the FDA does not know how many foreign companies are subject to inspection or how many are actively shipping drug products to the United States. According to Mr. Stupak, the FDA has variously placed that number between 2,100 and 13,800 during the last three months.

“How can we have any confidence the FDA is truly managing the risk that may come from foreign-made drug products if the FDA does not know the exact number of locations of foreign drug manufacturers?” Mr. Stupak asked.

FDA officials defended their role in overseeing foreign drug imports primarily through domestic inspections. According to FDA Commissioner Andrew C. von Eschenbach, MD, the agency screens all active pharmaceutical ingredients and drug products entering the United States to “establish whether … FDA has approved the drug product or the API [active pharmaceutical ingredient] is consigned to a plant that corresponds with its designated approval.”

The FDA has unveiled a new plan to decrease the current backlog of pending generic drug applications and increase the number of generic drug approvals the agency processes each year.

Although the FDA approved a record 682 generic drugs in fiscal year 2007, there is currently a backlog of 1,300 applications. “These applications represent a vast scope of products—and over half are still protected by patents. There is no way we could approve all of these applications,” said Gary Buehler, director of the FDA’s Office of Generic Drugs.

The agency will begin by reviewing outstanding applications and expediting those products for which there are no blocking patents or exclusivity protections. The agency will also expand the number of full-time staff dedicated to reviewing generic drug applications and will encourage generic drug companies to file more application materials online.

The Generic Pharmaceutical Association (GPhA) characterized the effort as weak and called for more extensive reforms of the generic drug approval process.

“Another initiative in name only simply will not get the job done,” said Kathleen Jaeger, the CEO of GPhA, in a statement. “What consumers need is for the FDA to address the core fundamental issues that are blocking timely consumer access to affordable generics.”

Linkback: https://tubagbohol.mikeligalig.com/index.php?topic=7596.0

One thing that I feel rather content in is the FDA's requirement of physicians to provide a 'medication guide'  to their patients before receiving ESAs. One major concern that many physicians-scientists have pointed out in several articles in the New England Journal of Medicine is the rising factors of patients actually demanding medical prescription being written by their doctors.

My immediate reaction was, 'when did patients start ordering around doctors?' And what is rather sad and ubiquitous about this is that many physicians acquiesce to their patient's demands for fear of harming the  business 'aspect' of the medical profession. At least the FDA processed regulations that can now willfully legitimize a physician's rejection of a patient's demands.

Its funny, because these kinds of cases result in patients suffering fatal sideffects; usually myocardial infarction or non-reversible central neural damage. The patient's family then sues the physician, who was the one who warned the patient in the beginning.

Do you see a major discrepancy in the system? Because I sure as hell do.
 

Linkback: https://tubagbohol.mikeligalig.com/index.php?topic=7596.0

Ate, what you have mentioned is the prevailing problem that continues to plague the medical industry here in the United States. As much as many doctors will not admit the fact that they are 'not in control', the contrary proves it otherwise. I have shadowed hospitalists as well as private-owned primary care clinics and have talked to many physicians about this and they all tell me the same thing "Medicine is medicine, but business is business."

The fact of the matter is that the drug industry controls the lobbying sector of the the United States, and as Health Insurance Industries take their control in the medical field, the realities of the situation is that physicians (excluding surgeons) have been suffering gradual decreases in medical reimbursements. Due to malpractice insurance cost increase, taxations, etc, physicians are forced to make their 'bread and butter' on the number of patients they treat per day. Originally, say 15 or so years ago, the medical reimbursement of physicians from the health care companies were probably 65%-75%, (this was considered the golden age of primary care), but in today's time, medical reimbursements can run as low as 45%-50%. That is a massive decrease in salary. Where primary care physicians were used to making $200,000 on relaxed 8-5 schedule, now they are forced to work double hours to even making 200-300 k (the average base salary of a primary care physician is around ~$165k, which is subpar for physician standards). I know an attending physician that works in the local hospital where I work as an ER Volunteer who complains about his student loans and debt--and the guy works 65-70 hours a week just to make 150k; 10-15 years ago, 'te, a primary care physician could make that amount by just working 40 hours a week.

The reason for this is the decreasing medical reimbursement. That is where your question comes into place. The fact of the matter that physicians are so reliant in high-patient turn-out--they are forced to establish a 'mutual' relationship with patients. Patients come to the primary doc (ped, fam prac, cardio, internist, ER med etc) for regular check up and frequent prescription refills. Some physicians, te--tho not all do this, bend backwards and will refill prescriptions for patients just for the purpose of maintaining that patient base. This is the 'business' aspect of medicine.

If it weren't for the appalling insurance situation of our health system, such kind of abuses wouldn't be present. I personally think that there needs to be some kind of revamping of the health care industry.
Less power for these drug companies and health insurance industries. They are raping physicians this way.

Ate, to answer your comment on PAs, the only reason for the rise of PA schools and Nurse practitioners is the fact that there isn't enough physicians in the United States. Our medical system is severely lacking. 300 million patient base--and there are only several thousands of doctors. PAs are there to fill in the ranks of insufficiency of doctors. The rise of Nurse practitioners is also a result of this discrepancy.

My personal remark: We need to focus more energy that invigorates the population to pursue the medical field. Increase student loans and subsidize loans for medical students. I will not deny the overbearing expense of pursuing a medical career--I myself have already accumulated $80,000 in debt just in loans for my undergraduate education, I expect to accumulate another $150k for medical school. Many students that could become great physicians simply choose not to proceed due to the difficulty in payment, loan offers, and the massive repayment; as well as the unfair medical malpractice and insurance rates that befalls on the medical student and medical resident intern.

Until the United States does something to solve and curve this problem, the problem will continue to manifest itself. To the detriment of the American people.

Linkback: https://tubagbohol.mikeligalig.com/index.php?topic=7596.0

Many people that I took classes with in basic pre-med science courses (biochem, molecular bio, organic chem, microbiology, genetics and evolution, ecology, physiology etc) started of as pre-med as I did, but due to the burden of debt that is mandatory in medical school and the difficulty of the MCATs, USMLEs, many have changed their career path. Though they stayed in the medical professional field. I know two good friends (whom I would be so daring to admit they were top notch students) who decided to go into  Physical Therapy instead of Medicine, another student ( close biochemistry study buddy of mine) who proceeded to go into pharmacy instead of medicine. I dont know why he did that since he was always so smart in the pre-reqs and since freshman year always showed a high interest in going to surgery. The fact of the matter is that other medical specialty professions (physical therapy, pharmacy, optometry, dentistry, podiatry, nursing etc) are experiencing increase of applicants. The monetary standards of those professions are also increasing, which is a powerful incentive for many students. I know that I was considering to pursue Podiatry instead of Medicine Proper, only because Podiatry offered a secure and optimally rewarding career path (they average ~160-250k). But you know, money isn't really everything. Thats one thing I realized. I'd rather pursue a career that I truly am interested and in love with than something that I didn't like but only for the monetary gain. Life is too short to live by that standard.

Ate, there is a two sided coin in medicine proper.

Physicians (non-surgical doctors) are experiencing this phenomenon more so than Surgeons.
Though the medical reimbursement of primary care physicians (gastroenterologist, cardiologist, family practice, pediatrics, obstetrics, emergency med, geriatrics, urologist, general internist, nephrologist, etc) has greatly decreased, the Surgeons suffer none of that. In fact, that is one of the reason why many medical students, upon passing their national boards and licensures, proceed to a surgical residency. It's the most rewarding (monetary, and hours). The average General Surgeon makes ~300k+, a specialized surgeon such as a cardiothoracic surgeon brings in an average gross income ~500-600k+; an orthopaedic surgeon can boast an average ~800k+, and a neurosurgeon can rake in 1-5 million or more. These are the reasons why more and more medical students pursue medical subspecialties and surgical specialties. This leaves a minimal and severely lacking amount of primary care physicians. I mean the logic is: Why do something for 60-70 hours and make ~150-200k, when I can work 50+ hours and make 2-3 times more than that? Diba? This is a rather discerning problem for the medical system. Hence, that is the many reason why the United States is importing hundreds of foreign doctors for primary-care positions to augment the already-limited amount of American primary care docs.

The way the health insurance companies dictate things; makes it impossible for any room to breath for primary care docs; that is why many primary care docs are actually leaving their field of specialty and taking up surgical residencies or specialty residencies that offer more room to  breath. (Monetary increase).

In all reality, we as a nation need MORE primary care doctors than specialized doctors because of the 300 million American patient base. But there are more specialized doctors than there are primary care doctors. This can be seen in the rural countryside, where there is 1 or 2 primary care physician to every 1,000 patients (there are worse scenarios). And most of the general population cannot afford the care of specialized physicians (hence, only those with health insurance or big bucks to pay co-pay can afford to see a specialized doctor). There are 40+ million Americans who do not have any form of medical insurance (many include young children, and the elderly). We cannot solve this now and government only exacerbates the problem, as can be observed by George Bush's recent veto of a bill by Congress to provide some kind of limited health insurance for young children (Bush also is influenced by health insurance lobbyist in Congress--who are oppose such a bill).

There is a severe problem in our system. Flawed.



Linkback: https://tubagbohol.mikeligalig.com/index.php?topic=7596.0