Five Rules Of Thumb About A New FDA Commish
10 CommentsBy Ed Silverman // November 11th, 2008 // 10:10 am
The ever-insightful RPM Report has a handy list of reminders as we ponder who - just who - might succeed Andy von Eschenbach as the next FDA commissioner. This is the sort of cheat sheet you may have come up with yourself, but you didn’t. So here it is…
1 - The FDA May Be Your Top Priority, But It’s Not Obama’s: There is a financial crisis under way, remember? “In this climate,” RPM writes, “priority goes to economic posts.” You know, the Securities and Exchange Commission and the Treasury Secretary. Besides, the Centers for Medicare & Medicaid Services is usually filled first. And as a post confirmed by the Senate, naming a new commish is guaranteed to take months. So let’s see, about 12 months from now…
2 - It’s Not Necessarily Obama’s Pick, Anyway: Typically, there is some to-ing and fro-ing between White House staff and the new Health and Human Services Secretary when it comes to filling the FDA post, RPM notes. But we don’t know who will head HHS either. And thanks to the uncertain health of Ted Kennedy, the chair of the Senate Health Committee who has historically played a key role in choosing a commish, the process may get still more complicated if he steps down.
3 - It Won’t Be An Insider: Remember a theme from Obama’s campaign? It was ‘change.’ Choosing Janet Woodcock may not make sense because, as RPM correctly points out, this is a plum post and there are just so many jobs to award the loyal and faithful. And since she’s already seen as the industry choice, that may actually be a strike against her. If she becomes a flashpoint and prolongs the process, that only works against pharma, anyway.
4 - It Might Be Nissen: Well, maybe. Nothing more than speculation here, but RPM believes the “widespread suggestion that the Cleveland Clinic’s Steve Nissen would be the worst for industry doesn’t hurt him.” As you know, as an Obama advisor he has already been vetted in case he is picked for something.
5 - Nissen Might Not be so Bad After All: Yes, he’s unpopular among many in pharma (see our reader poll), but RPM posits there are reasons he may not be so terrible for the industry. As an insider, he can’t drop bombs anymore, but has to work inside the system. Despite accusations of bias, he actually is closely involved in drug development, since the Cleveland Clinic runs trials.
“Last but not least, there is the Kessler effect: the last time a commissioner was appointed who defined himself by making enemies in industry, he also gave the agency the credibility it needed to establish accelerated approval and the user fee program,” RPM concludes. “Kessler was never popular with industry, and drug companies celebrated his departure. But drug approvals have been in steady decline ever since. Coincidence or not, those were the good old days.”
Thanks to The RPM Report
Justice in MI
I agree with this analysis (wudda i know?), but would amend the last bit about Kessler. Gingrich, big tobacco, and the Washington Legal Foundation, and friends ran full page ads in the NYT and WSJ calling FDA, and Kessler in particular, a murderer and a thug. Pharma joined in until it became too much for them (and, indeed, some became aware that trashing the FDA to that degree, and Kessler specifically, was trashing their own ’seal of approval’).
Most of this probably came from Kessler’s attempts to regulate tobacco - Dan Troy was a point person against that - than his role re: pharma.
PaulGGG
You cannot have someone who cares more about making a name for himself than about balancing all parts of this complex job. I am afraid Nissen fits this description. He has shown a bias to crucify things he has not been involved in (avandia, vytorin, etc.) and defend things he’s been part of (including making lots of money from) like Pfizer’s torcetrapib.
Thom
Why not Nissen?
An FDA Reviewer
No matter who the new commissioner will be, he or she will be constrained by what they will be able to do, especially in the short run. Assuming that the new commissioner really wants to and the appointment has not been excessively influenced by the representatives who have close ties to Pharma. Even so he or she needs to get settled, he will be limited as to placing his own people in very quickly, and he will be constrained by anything that requires a public comment period, new laws, or lots of money.
There is also the issue of an interim acting commissioner. I have some thoughts but will not address them here.
However, there are some things with regard to structure and process that can be done immediately, along with those things that can be done in the short term or where the process can be begun. In addition there are some very practical concerns regarding the internal environment.
1. Think about who you can trust. Many of the people in FDA management currently got there by being very industry friendly, and even may have gone out of their way to inappropriately help industry. Be careful of those at various levels who have been promoted over the last few years, and are in the line of succession. Be very careful of those who are in critical positions, such as setting scientific and regulatory policy or are intermediaries between the primary review groups and specialized review functions, such as post-marketing surveillance and safety and who control the flow of information.
Be cautious even with whistleblowers and those who stood up for patient safety. These individuals may have been subjected to intense harassment and retaliation for years. You will need to assess if they are able to keep their personal feelings in check and whether recommendations and comments are personal vindictiveness and/or excessive or in the best interest of healing the FDA and protecting the public and if they can work with people who may have harmed them in the past, but who may be able to be included in the repair of the FDA.
2. Prioritize. For review areas look at those disease areas that are or will be economically most important for big Pharma, including cardiovascular, endocrine, psych, oncology, pediatrics, safety, critical path initiatives.
3. Listen to the front line review staff. Especially those who have been at FDA 10 years or more, have outstanding credentials and evaluations (except perhaps recently or in areas required for them to advance), and yet have not advanced or even have been allowed to train to advance. Open upwards communications.
4. Look into management policies and procedures, (MaPPs). MaPPs such as scientific disputes feed back into evaluation by the same people who may have been the source of the disputed.
5. Look at the EEO office. Contact information could be posted and could easily be made available on the internal web site.
6. Look at the process for Risk Management Plans that are required under FDAAA 2007. Presently evaluation is by review areas not involved in the primary review, or who have expertise in the drug class, and who sign off on the RMPs before the safety data is even reviewed.
7. Guidances are not required to be followed by sponsors but are required to be followed by reviewers. A senior level appeals process for not abiding by guidances on an individual case may be appropriate until the scientific validity of guidances can be reevaluated and guidances changed.
8. Communications with sponsors towards the end of the review cycle need to be more tightly controlled. Inappropriate communications can allow insider trading or activity to bypass reviewer concerns.
9. Industry complains that FDA reviewers are not up on the latest science. This can be corrected by adequate training. For example so much data is coming in yet there is no mechanism to adequately train reviewers to become even minimally familiar with the control language of the programs required to manipulate the data and do statistical analyses. Pull down menus, preset procedures, and 2 hour seminars are simply not adequate. Weekly classes with hands on training and homework in the basics of the control language are needed.
10. Provide reviewers with the computer programs they need to do their jobs. There is no excuse for any drug reviewer to not have chemical drawing programs, and graphics packages.
11. Reevaluate required automated data analysis programs. Setting up the inputs and getting a canned 20 page output that doesn’t perform the clinically relevant analysis that can be presented in 1 – 2 pages is not appropriate, is inefficient, and may miss the clinically important issues.
12. Allow flexibility on the required NDA review format. Using the same canned review format does not allow the presentation of the review to flow in an appropriate manner, and is wasteful in terms of time and resources.
13. Have each reviewer and team leader sign off on an NDA and not just the medical division director. Each review discipline is needed for their particular expertise as to safety and efficacy. It is not appropriate to tell review staff that they may only say acceptable or nonacceptable so that the medical director can inappropriately overrule them with no fear. Also have each review discipline enumerate the specific reasons for nonapproval including the legal basis in the FD&CA and train reviewers in these reasons. Have each review discipline completely responsible the nonapproval/letter. Management leaving out safety concerns that are the basis of a nonapproval unacceptable recommendation allows companies to avoid addressing safety concerns.
14. Industry Meetings. Allow review staff to determine the need for industry meetings, discussing the same issue over and over so the sponsor can try to get the answer they want is not productive. Eliminate preliminary responses before the meeting that allow the sponsor to call up upper management to intervene or to cancel a meeting so they won’t get a full response that they may not want, or so they can have management exclude a particular review discipline or send the same question to a specialty review group. Without input from the primary reviewer who has already caught a problem.
15. Have primary reviewers from all review disciplines evaluate studies and meeting packages. Exclusion of clinical pharmacologists from evaluating first in man studies, and the clinical pharmacology development program until after it’s been completed is not appropriate an results in having to live with non- or poorly informative data.
16. Eliminate the excessive and onerous tracking of NDA reviews. Forcing reviewers to agree that information is adequate or that studies don’t need to be reviewed and documenting every single agreement including timelines before the reviewer is able to even evaluate a submission is inappropriate. Having up to 16 people track a single reviewer doing the NDA review is a waste of resources.
17. Use some of the big influx of temporary funds to move different review disciplines back to working side by side with each other.
18. Contact the people who have left and find out why, especially those with over 5 years of experience and in critical therapeutic areas.
19. Look into pediatric drug development. It’s not appropriate to allow companies not to begin developing pediatric formulations as soon as possible and then accept the adult strength at the last minute when exclusivity is about to run out. Also using population pharmacokinetic analysis with sparse sampling that and can’t even distinguish between an IV Push and oral absorption is inappropriate especially when it’s done during the efficacy trials after the exposures relative to adults should have already been determined. Other details including small numbers of subjects and including 200 lb. 12 year olds also need to be examined.
20. Computer filing systems need to be looked into. Automatically generated e-mails that don’t even include a drug name, etc. or that have 5 different numerical coding systems over the course of a drug’s development that have no correlation to the IND or NDA submission number is clearly counterproductive.
21. Allow union representatives as independent third parties at scientific review meetings. A single reviewer in a room with 6 or more managers who pressure the reviewer for hours for a specific answer, frequently even before the data has been looked at is not appropriate.
22. Think globally. Have the reviewers for NMEs and important clinical issues write up a brief analysis of the issues and distribute them to all review staff. If one reviewer finds problems that are really a class or cross class effect there’s no reason other reviewers working on the same types of drugs shouldn’t be aware of it. Reliance on managers who want to approve all drugs results in postmarketing safety problems that could have been avoided.
There are some things that can only be taken care of by Congress changing the law and will take time. For example the length of the review clock, and certain aspects of the process.
Another example is the Physician’s Labeling Rule (PLR) including the reporting of adverse event rates. The PLR that recently went into effect combines Warnings and Precautions sections so it becomes difficult to determine the real level of concern and what needs to be done about a safety problem. It also prevents the recognition of when the level of concern has been upgraded.
Most important for Congress is the review clock. A 10 month standard review is now too short with the amount of data submitted. For an NME that an Advisory Committee needs to be completed at least 1 month prior to the PDUFA due date and takes 2 months before hand to get ready for. This means that each review division that feeds into the next needs to be completed in turn. When all the lead times are added up this is just too short a period.
I know this is a lot but it’s not everything. Industry has been working toward complete control of the review process for a long time.
An FDA Reviewer
Sophie
How about the standout, honest insider and whistleblower, Dr. David Graham. That ought to give Pharma a bit of a hernia - which they so amply deserve.
Justice in MI
Great comments, FDA Reviewer.
I wonder if you know the “employment status” of long-time senior FDA management people (no need to name names) under a new Commissioner.
Is there some ‘everyone hands in their resignation’ process and we’ll see, or do such people have more or less automatic tenure unless they have definitively messed up?
Ima Misfit
President Obama should give this post the respect it deserves by nominating someone with the ethics and integrity of all those who’ve filled the position over the past 25 years - he should nominate Porky Pig.
harry
i don’t know much about Nissen except for reading about the meta-analysis and the associated publicity. I also saw him on television , where he was part of a panel of well known cardiologists discussing heart disease. I just noted that the rest of the cardiologists promoted exercise, healthy food as first line against heart disease but Nissen promoted Pfizer’s torcetrapib. A few months later Pfizer pulled the drug. He obviously wasn’t looking at that data too closely. it will be interesting to see if Obama can make the right change. It will be a high profile litmus test of his policies.
PaulGGG
Harry,
Very good observation. That’s the problem with Nissen and his old boss Topol. They have been very aggressive against others (companies and scientists) who did not agree with them, and aggressively promote themselves and their projects.
Not that he hasn’t done a good job in some things, but he’s far from squeaky clean and has tons of enemies and people who dislike him in all circles, beyond pharma.Not sure how productive that would allow him to be.
An FDA reviewer
Justice,
People definitely have tenure unless they have definitely have messed up.
The industry plants are so widespread and so deep and even people who might be let go are leaving voluntarily and putting their replacements in place (Von Eschenbach’s succession planning) who don’t have as obvious histories.
I would suggest the commissioner look at who is active in outside professional organizations especially industry related organizations, senior level scientists who have recently joined. New reviewers with ties to academicians with big time industry contacts. Those who are listed on publications re: safety with people like Tom Laughren, and who gets to present at Drug Information Association Meetings. For example a good meeting to look at is who presented at the presented at the Jan 24 -25 2007 FDA/DIA meeting on drugs disease modeling. This included modeling of drop outs in diabetes, Parkinson’s Disease, Cancer, and Depression. All big $$ diseases where manipulating assumptions on the drop outs and the disease model can have big payoffs for industry.