Latest Drugwonks' Blog
FDA’s new proposed review model would break the process into four distinct phases:
FDA's Proposed Four-Stage Review Cycle |
1. Administrative phase – The agency would validate the application before the review clock starts. 2. Application review phase – Primary and secondary reviews would take place along with the issuing of any discipline review letters. 3. Information sharing phase – The sponsor and the agency discuss how to address issues raised during the initial review. 4. Wrap-up and action phase – Final review activities would be completed. |
Under the proposal the agency would not need some extensions it had previously suggested only because the review clock would be stopped mid-review to address application problems and amendments.
A delay by any other name. This is progress?
The mid-review pause would allow for in-depth discussion between the sponsor and the agency, and appears to be in part a response to an industry request that the review system in the next user fee cycle include a process that makes it easier for sponsors to gain feedback and provide input during an application’s review.
Minutes of an Oct. 12 Prescription Drug User Fee Act negotiation with industry indicated that phase would be used for sponsor meetings with FDA and amendment submissions stemming from reviewers’ issues. The information sharing phase was proposed as a fixed period, although no specific length of time was given.
It would almost certainly be the period where FDA would call its time-out, where the review clock would stop while meetings were conducted.
An application review cycle would begin with the “administrative phase,” where the agency would validate the application before the review clock starts. Primary and secondary reviews would occur in the “application review phase,” along with the issuing of any discipline review letters.
After the sponsor and agency complete the “information sharing phase,” the agency would move to the “wrap-up and action phase,” where final review activities would be completed, including advisory committee meetings, sponsor amendment reviews, risk management agreements, if necessary, and a final decision.
FDA has not determined many details of the new model and minutes called it a “high-level concept.” The agency has not worked out whether the “information sharing phase” would be required for some types of applications that would be considered very likely to be approved or receive a “complete response” letter.
The agency also warned it has not finished refining the concept, so it may not appear superior to the existing review model as it comes into focus. Industry groups at the meeting planned to discuss the new model with their member companies before the next meeting.
The new model is different from any previous compromise FDA has proposed. Agency representatives said in earlier meetings they needed more time than the original PDUFA periods and argued for automatic extensions if advisory committees, foreign facility inspections or certain types of Risk Evaluation and Mitigation Strategies were necessary. The agency also has said any major application amendment should trigger an automatic three-month deadline extension.
Talk about a 90 degree angle!
Under the new review model, the agency would not need three-month extensions for advisory committee meetings or foreign inspections. But it did say a four-month extension still may be needed if complicated REMS was submitted during the review cycle.
Ah – but when during the review cycle should also be a PDUFA reauthorization topic of discussion.
The agency does appear somewhat willing to allow for more Type C meetings in a review cycle, as long as it can control them. “Control” means that the FDA would determine whether a C1 or C2 meeting was appropriate. Industry said sponsors should be allowed to request either classification of meeting, but the agency said it wanted to preserve the standards of what constitutes a Type C meeting. Those standards could be lowered if industry determined the meetings, according to the minutes.
The agency also was concerned the demand for Type C meetings could balloon enough that it would overburden review staff. If the number of meetings eclipsed the 2003 record, the PDUFA workload adjuster, which helps determine annual user fee amounts, would not adequately account for the increase, according to the minutes. If industry accepted the C1 and C2 meetings, the agency said it wanted more resources added early in the PDUFA V cycle to address the workload problem.
Sounds reasonable – but what about a “real time” meeting measurement system to measure if money earmarked results in meetings scheduled?
And what about the issue of so-called “non-binding advice?”
The agency was concerned any provisions allowing non-binding advice would force primary review staff to give advice without supervisory approval or an official record, which could cause an increase in FDA-industry disputes.
Allowing non-binding advice also likely would increase reviewers’ workloads. The agency said some questions that seem simple require input from several reviewers and cannot be answered by one reviewer, according to the minutes.
FDA remained leery about the idea, but was willing to talk about specific parameters where the general scientific discussions that carry no regulatory weight could be allowed, according to the minutes.
Really? Non-binding advice that carries no regulatory weight?
This is progress? This is transparency?
What does “drug safety” mean? All drugs have benefits as well as risks – and that’s why we have, for example, REMS and early safety signal communications (worts and all) as well as the FDA’s “safe use” initiative (wherein a drug is made safer when it is used as intended).
But the unsung hero of “safety” is “quality.”
I recently was invited to visit Pfizer’s Kalamazoo production facility. I expected “yawn” – but what I got was “gee!" -- as in GMPs.
What impressed me more than the gee-whiz production aspects of the facility (of which there were plenty) was the dedication of the people who work there – top to bottom. It actually reminded me a lot of the FDA. Long-term employees dedicated to serving the public health through dedication to quality. And they all took it very personally. Just like at the FDA, the Pfizer folks (many of whom were not only Upjohn legacy employees – but the sons and daughters of Upjohn employees) were on personal missions of quality. There was a lot of pride on display.
It was all about quality 100 ways to Sunday. And innovation.
But innovation with a twist.
The Kalamazoo facility makes (among other things) the API for methyl prednisolone, a corticosteroid long off patent. In fact, it’s been around for about 50 years. To my surprise, the Kalamazoo plant exports the API to both China and India.
A US manufacturing facility of an innovator biopharmaceutical company exporting API to China and India for profit? What’s wrong with this picture?
Well, as it turns out, it’s what’s right – innovation through manufacturing prowess, organic chemistry smarts and green technology. Better. Faster. Cheaper.
And also safer – since Pfizer’s figured out how to manufacturer it without preservatives.
Obvious implications for generic manufacturing standards as well as FOBs.
Pharma’s always bragging on its ever-growing investment in R&D. But when’s the last time you heard about investments in domestic manufacturing? Probably never. And when’s the last time you read about enhanced drug safety through cGMPs and cooperation between industry and the FDA? Not recently. That’s a shame because they’re two important stories.
Sound like an infomercial? Request a plant tour and see for yourself.
For more details on the Kalamazoo facility, see here.
www.npr.org/blogs/health/2010/10/28/130881430/unpleasant-future-looms-for-nice
by JOANNE SILBERNER
Critics of one of the most controversial parts of the British health system may lose their target in a few years.
The National Institute for Health and Clinical Excellence (happily called NICE by critics and supporters alike) decides whether medicines are cost-effective. If NICE says a drug provides too few benefits at too high a price, the National Health Service in England and Wales generally won't provide the drug.
At a drug industry trade group meeting in London earlier this week, Health Minister Lord Howe, Under Secretary of State for Quality, said NICE has become "redundant," and that it should focus on setting quality standards rather than evaluating individual drugs.
NICE has been held up by American critics as an example of what happens when the government rations medical care. There have been complaints that Brits dying of cancer weren't able to get the latest treatments. Another controversial decision from NICE led to restrictions on Alzheimer's drugs that are now being relaxed.
Many folks in England and Wales accept NICE's decisions without complaint, but others have railed against them. The national government as well as local divisions of the National Health Service have on occasion overridden NICE.
Meanwhile, in another blow to the agency’s reputation, the government has said that it's providing £200 million ($318 million) to the NHS to pay for several cancer drugs that NICE has deemed unworthy.
Lord Howe says NICE's advice will still be taken into consideration. But some close watchers of NICE are predicting the agency will be gone by 2013.
While NICE's loss of power would deny headline writers some of their best chances for bad puns, the drug industry may not be completely off the hook.
Lord Howe says the government is working on a new agency that would set drug prices based on a "value-based pricing system." With no details yet available, that could be good news or bad news for drug companies.
Let's repeat that: But some close watchers of NICE are predicting the agency will be gone by 2013.
The NHS knows it has an innovation and quality of life problem because of rationing. Meanwhile in the US the Berwick led CMS is seeking to:
1. Limit how many diabetes testing strips doctors can prescribe each month.
2. Is taking a year to see if it will pay for Provenge, the prostate cancer vaccine.
3. Seeking to restrict what biotech drugs patients can get to what Medicare deems the least costly alternative.
4. Telling hospice patients how many days of care they can receive and what they can receive.
Congress should follow the British example and give the newly created comparative effectiveness bureaucracy the pink slip and eliminate all funding for CER.
Yes Minister.
The British Health Minister, Lord Howe, has affirmed his government’s position that NICE has become “redundant” and would be “moved gradually away from single health technology assessments towards the formulation of quality standards.”
NHS bodies are currently obliged to follow (or at least consider) NICE guidance but the changes will mean its cost-effectiveness reports will in future be purely advisory.
According to his Lordship, “In terms of cost-effectiveness, even though we will rely on NICE’s advise, we will move onto our own value-based pricing system.” He added that the coalition government wants to ensure patients and the NHS are allowed access to the medicines they both want and require.
Lord Howe said: “So that there is no doubt, the current terms of the PPRS (Pharmaceutical Price Regulation Scheme) pricing system will be upheld in full until it comes to an end in 2013,” but after this it will be replaced by the government’s evolving definition of value.
Lord Howe: “We need a much closer link to the price the NHS pays and the value that a new medicine delivers.”
For more on value-based pricing, see here.
When the new Congress begins its hearings on ways to really reform the US healthcare system, the British decision to denude NICE should be raised relative to many issues – not the least of which is the role and responsibility of PCORI (the Patient-Centered Outcomes Research Institute).
This isn’t the end of QALY-based cost-effectiveness, nor is it the beginning of the end of CATIE/ALLHAT/STAR-D comparative effectiveness – but it is the end of the beginning of a cost-based care philosophy that places the short-term needs of payers (be they public or private) over the long-term interests of patients.
Outcomes-based clinical effectiveness – now that would be (lower case) nice.
Food & Beverage Industry Announces Front-of-Pack Nutrition Labeling Initiative to Inform Consumers and Combat Obesity
(Washington, D.C.) America’s leading food and beverage manufacturers and retailers joined forces today in the fight against obesity and announced their commitment to develop a new front-of-package nutrition labeling system. The unprecedented consumer initiative will make it easier for busy consumers to make informed choices when they shop.
This program will add important nutrition information on calories and other nutrients to limit to the front of the packages of many of the country’s most popular food and beverage products. To appeal to busy consumers, the information will be presented in a fact-based, simple and easy-to-use format. In the coming months, the Grocery Manufacturers Association (GMA) and the Food Marketing Institute (FMI) will finalize the details of the initiative, including the technical and design elements. In addition, details will be finalized on how to provide consumers with information on nutrients needed to build a “nutrient-dense” diet and on “shortfall nutrients” that are under-consumed in the diets of most Americans. GMA and FMI will continue to consult stakeholders on these and other details in the coming weeks.
Consumers will begin to see the new label in the marketplace early next year.
To build consumer awareness and promote use of the new label, America’s food and beverage manufacturers and retailers have agreed to support the change to their product labels with a $50 million consumer education campaign. The campaign, to be launched in 2011, will be aimed at parents who are primary household shoppers.
Acne Cream? Tax-Sheltered. Breast Pump? No.
By DAVID KOCIENIEWSKI
Published: October 26, 2010
Denture wearers will get a tax break on the cost of adhesives to keep their false teeth in place. So will acne sufferers who buy pimple creams
A breast pump and various accessories can run about $500 to $1,000 for most mothers a year.
People whose children have severe allergies might even be allowed the break for replacing grass with artificial turf since it could be considered a medical expense.
But nursing mothers will not be allowed to use their tax-sheltered health care accounts to pay for breast pumps and other supplies.
That is because the Internal Revenue Service has ruled that breast-feeding does not have enough health benefits to quality as a form of medical care.
You can't make this stuff up...
www.nytimes.com/2010/10/27/business/27breast.html
“Anyone who isn’t confused really doesn’t understand the situation.”
-- Edward R. Murrow
On November 2nd, from 12:15-1pm the FDA is holding a teleconference to discuss the agency’s risk communications research agenda.
45 minutes?
The teleconference will begin with a presentation by the FDA on its research agenda and its role in supporting the agency’s strategic plan for risk communications by “strengthening the science of risk communications.”
This will be followed by a panel of FDA’s social scientists and a Q&A.
FDA and social science? Maybe 45 minutes begins to make more sense.
Be there or be square.
“The speed of communications is wondrous to behold. It is also true that speed can multiply the distribution of information that we know to be untrue.”
-- Edward R. Murrow
Talk about biting the hand that feeds you. Puerto Rico, long home to pharmaceutical manufacturing facilities, has just passed a new law (Law 154) that imposes “special taxes” on non-resident companies. That means all of the “Big Pharma” firms doing business on the island.
According to a 2006 survey, the biopharma sector supports over 94,000 jobs in Puerto Rico and conducted 425 clinical trials on the island commonwealth.
It should also be noted that Law 154 was enacted minus any public input or comment.
Adios.
From Business Week:
"A key U.S. Senator is asking federal officials to investigate after reviewing data that shows doctors across the country prescribing alarmingly high numbers of powerful mental health drugs paid for by Medicare and Medicaid..
Grassley did not name the doctor, but state records obtained by The AP show Dr. Fernando Mendez-Villamil wrote an average of 153 prescriptions a day for 18 months ending in March 2009. That's nearly twice the number of the second highest prescriber in Florida, who wrote a little more than 53,000 prescriptions, according to a list compiled by state officials.
The doctor's attorney, Robert Pelier, said his client tried to contact Grassley to explain the data but got no response.
"Dr. Mendez-Villamil is a specialist that has treated the most afflicted and poor in the area" and has never acted improperly, Pelier said. He filed a lawsuit against the state alleging authorities tried to terminate him from being a Medicaid provider "without cause."
Federal officials said they stopped reimbursing Villamil after Grassley inquired about the doctor to HHS in December."
Nice work. And welcome to another aspect of Obamacare: Targeting and terminating payment of doctors who are fingered by the feds for providing "too much" treatment.. Having Grassley serve as a bounty hunter is optional.
I thought it would be nice to hear Dr. Mendez-Villami's side of the story since most media accounts gloss over it. I found this letter he wrote to HHS. You tell me if this sounds like a crook or just one more honest and hardworking doctor who will ultimately bag Medicaid because of the reimbursement cuts and threat of retaliation.
PS.. Here's something CMS and Grassley overlooked: No one gets rich writing prescriptions.. Where is the fraud. Is it a criminal activity to prescribe more than what a Senator regards as "normal?"
Why isn't anyone raising hell about this abuse of power?
Dear Senator Grassley,
I am writing to add a human face -- along with some background information and context -- to whatever image you may have of the doctor in Miami who wrote all those prescriptions for mental health drugs.
I am that doctor. My name is Fernando Mendez-Villamil and I have practiced psychiatry in South Florida since 1998. I received my medical degree from the Universidad Central del Caribe in Puerto Rico and performed my residency in psychiatry in Jackson Memorial Hospital, the public medical center serving metropolitan Miami.
I can only imagine what you thought when you were given information by the Florida Agency for Health Care Administration showing that one doctor wrote close to 97,000 prescriptions for mental health drugs over 21 months. This came to 153 prescriptions a day, 7 days a week for that entire period; twice as many prescriptions in that period as the number 2 Medicaid prescriber in the state.
These numbers may have struck you as an indication something was wrong. Frankly, since I have never stopped to do such a calculation, it seemed a little peculiar to me too. I never felt I was treating an extraordinary number of people or writing an exceptional number of prescriptions.
At the same time, I never thought I would be faulted for working hard or for being very organized and efficient. But now - with this publicity and the questions it has engendered - I have looked at the matter carefully and would like to provide you and the public with some context within which to consider these facts.
First, I want you to know that I take very good care of my patients. My top priority is to improve their conditions. In more then ten years of practice I have worked with thousands of afflicted individuals. Their conditions have ranged between mild emotional upset to extreme debilitating psychosis.
By every indication, my patients and their families are pleased with my care.
I may be an oddity as a physician because I do not play golf, I do not have a boat and I seldom leave my practice for extended vacations and am involved in my practice on a daily basis. That is not to solicit sympathy or to appear “noble.” I am simply committed to my patients, profession and enjoy what I do and do not seek distractions.
As to my patients, they share some characteristics.
* Many receive a combination of medications with each drug addressing specific aspects of their condition identified by the use of objective clinical findings along with subjective complaints. Therefore, when I see such patients I must write or renew an average of three or four prescriptions.
* Some patients come to me after having been under the care of other medical providers who prescribed some of these medications. I must evaluate whether those drugs are effective in achieving their treatment objectives, whether some medications should be discontinued and whether additional medications are required. This can be a very difficult process when I am dealing with a mentally ill patient who may not be able to assist fully in the examination process. I would like you to know that these efforts are in combination with initial and ongoing psychiatric assessments of my patients.
* Ongoing treatment plans with the use of atypical antipsychotic medication is necessary in order to maintain patients stable and effectively responsive to their mental health needs. I firmly believe that a person’s health should not be placed in danger by erratic or ineffective treatment.
* As a result of my assessments and treatment plans I have initiated; most of my patients are very stable and experience very few changes in behavior or in their medical condition over time. Of great importance is the fact that hospitalization rates of my patient population are less than 1%. Hospitalization can be costly and otherwise interrupt the mental health and wellbeing of the patients. While I seek to be alert of subtle variations in my patient’s responsiveness to the treatment or behavior that might indicate a need to alter their regimen, you may appreciate that my patients are not always able to reliably explain how a drug is affecting them. Chronic mental health patients require complex combinations of medications based on their past treatment, physiological and psychological needs.
As to the specific prescriptions I have written, I have asked the Florida Agency for Healthcare Administration to provide me the information that was presumably provided to you and consequently to media outlets. The department has responded to my request by saying they have not received any recent requests for information about me or my practice and could therefore not furnish me with such information.
The information received from this agency advised that I am not under any sort of investigation. It also appears that the circumstances surrounding the release of the information to you supports this also. This was good to hear because I would hate to think that the government would discourage hard work and efficiency in the delivery of medical care.
In a similar vein, I was very surprised to read in the Miami Herald that Medicare had supposedly stopped payment for my services; and I am very pleased to confirm with Medicare officials that this was NOT true.
As to the numbers of prescriptions that have been cited, let us look at them on a hypothetical basis and see what they show.
Assuming the numbers are correct, I wrote 97,000 prescriptions in 21 months.
AHCA does not indicate how many patients were involved. However, again assuming those numbers are correct I believe the following would outline the pertinent facts in this matter.
Spread over 21 months, on an average six day, sixty to sixty-three hour work week that comes to approximately 4619 prescriptions per month. It is also not uncommon for me to actually work beyond these hours if there patients that need to be seen; as my practice is mainly a walk in, first come first served office.
At my average work schedule of 22-24 days per month, that means I saw between 47-55 patients a day and wrote an average of 210 prescriptions. That averages to 2-3 prescriptions per patient per appointment. Please remember that most of my patients are seen every other month; are given refills and my services are focused on the ongoing administration, effectiveness and responsiveness of the medication treatment plan I have prescribed for these patients. Time wise, I average 10-15 minutes per patient.
Generally, I work an average workday of 11-12 hours. Not counting one hour in the aggregate for lunch and other non patient related activities, I see roughly four patients per hour.
Given the stable nature of my patients –these efforts are reasonable and well within the norms of modern psychiatric practice and in treating my patient population. This is especially true given that mine is a psychiatric practice that rarely involves time-consuming psychotherapy, physical contact or examination of the full range of vital signs. Please keep in mind that the interaction I have with my patients is a combination of patient assessment, monitoring and evaluation of a continuing course of treatment as to the effectiveness of the patient’s medication regimen and/or treatment.
Senator, I certainly appreciate your efforts to monitor matters such as this. Our country’s health care system is vast and complicated and seemingly includes much inefficiency. I hope you continue your good work with vigilance and determination.
However, in my case I assure you there is absolutely no cause for concern or alarm.
And I probably COULD use a nice vacation.
Respectfully,
Fernando Mendez-Villamil, M.D.
EMAIL: mendezvillamildr@gmail.com
cc: The Honorable Kathleen Sebelius
Secretary, U.S. Department of Health and Human Services
Charlene Frizzera
Acting Administrator, Centers for Medicare and Medicaid Services
U.S. Department of Health and Human Services
The Honorable Thomas W. Arnold
Secretary, Agency for Health Care Administration
State of Florida
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
