New Powers for the FDA?

Fierce Pharma had a piece yesterday revealing a new measure introduced in the House recently in the wake of the J&J recall hearings by Rep. Edolphus Towns (D-NY), calling for the FDA to have power to initiate its own recall rather than having to wait for the drug maker to do it.  Senator Michael Bennet (D-CO) has produced a bill of his own in the Senate that echoes the House bill's call for more power, including more agency oversight of foreign drug manufacturing.  In either case the legislation has a long way to go and can expect significant heel-digging by PhRMA.  It's all here.

More Student Advice

A lucky former student recently asked some advice on how to give notice at a job she loves, for a job she hopes will propel her career to new levels.  Here is my response.

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Congratulations! This is a very exciting time in your career, and I am gratified to be along for the ride.

I completely understand and empathize with the misgivings around giving notice to an organization that you have enjoyed working for, and where you got your early development opportunities. I have been there myself and it can weigh heavily on your heart. Here are a couple of thoughts that have helped me over the years.

1. Any good manager will understand your reasoning in leaving for a good opportunity, especially if that manager cannot create the same opportunity for you herself. No good manager would think of holding an employee back or resenting her for taking the next move in her career. A good manager needs to think about the team's best interests too, and realizes that letting you go in anything other than a head-up way would send a poor message to the remaining team members, and that would eventually undermine team cohesion.

2. Of course the above would not necessarily be true if an employee has been dishonest with her manager, or leaves before 'giving back' after having been trained. Managers don't appreciate promising employees who leave too soon. But this isn't the case with you; two-plus years in an organization is about the norm these days.

3. Leaving your current organization will create an opening for someone else to step up and show what they can do. In my early days as a manager I really worried if one of my stars left, but I came to see that there were always others waiting in the wings, ready to step in. Your departure may even create a job that someone from the outside can fill, giving someone a badly needed first chance as you got two years ago.

With all that said, my advice for you when the time comes is to tell your manager what you told me: that you value the opportunity your current job gave you and that you have enjoyed the organization and feel that you made a significant contribution, and now it is time to take the next step in your career. Be forthright and honest, describing why the next opportunity develops your career in the way you wish it to go. Offer to help train your replacement and be diligent in handing off your duties. For the reasons I stated above, your manager should accept your resignation graciously and send you on your way with her very best wishes and with the relationship very much intact.

On the remote chance that this does not go well, that there is resentment or ill feelings left behind, you need to know that you did everything right. That ultimately you cannot control what other people think or do, you can only control your own behavior. If you handle this professionally and honestly, you need not fear reprisals or burned bridges. As you say this is a small community and our colleagues have good instincts about these things; they will be able to judge for themselves that you handled yourself correctly in this episode. Remember that only you are in control of your own reputation and brand; no one can successfully pass untruths about you for very long. If you handle yourself professionally the ship will right itself - it always does.

Big Pharma Wants to Buy You Lunch

Jessica Wapner of Slate explains how the pendulum may have swung a bit too far in this piece on the value of industry sponsored medical education, here.

The latest in the Pfizer/Trovan saga comes down from the US Supreme Court today.  The Supremes have kicked the entire mess back to the lower courts by ruling today that it won't stop Nigerians from suing Pfizer in the US.  Technically they didn't rule so much as declined to hear Pfizer's appeal of the lower court ruling from last summer.  We have run down this story a couple of times on this blog, here and here.  Pharmalot's take is here.

Career Question

A former student wrote to tell me she had a chance to take a year long consulting job at a very big stable company, although it would mean leaving her current job that she had held as a headcount for a long time, and she asked my advice.  Here is an excerpt of my reply. 

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The question you are asking yourself is exactly the right one: do I leave something comfortable and reasonably secure for the possibility of an even better job, knowing that I am stepping into the unknown and could eventually lose more than I gain?

In rock climbing, going from handhold to handhold is one thing. But sometimes the next hold is far enough away that you actually have to jump to it, meaning you have to let go of the rock for a split second to get where you want to go, risking a serious fall. This is called a 'commitment move', and that is a good analogy of where you find yourself right now.

Sometimes we think in terms of 'secure' versus 'not', as though having a headcount job now means that job or the next one will be there as long as we want it. But that is often not true: the job that seems solid now can  disappear in a flash if the company goes into protect mode. No company, even the good ones, is so loyal to its employees that it will sacrifice its financial health to keep its employees secure. If there is a choice between the company or the employees, the company will survive. They can always get new employees; it is a buyer's market.  So the choice is not as black and white as secure versus the unknown. There is risk in staying, too. That might make it easier to think about.

In addition to your taste for risk, think about your long-term career goals. Where do you see yourself in 2 years, 5 years? What job would you like to be doing, and does your current position provide you with a path to that goal? Have you had that conversation with your manager? Does going to a large company as a consultant take you closer to that goal? Are you okay with being content, or do you want to check out the grass on the other side of the fence?

And a final thought: your current position is in a smaller organization. Where you are thinking of going is the very definition of a giant organization, and it is quite different to work in that culture. That is part of its security, but it can come at the cost of some autonomy in the job role: every decision gets processed through a long chain before it can be acted on, and that can be frustrating. You may not know how you feel about that until you've worked in it for a while, but it is something to think about nevertheless.

This is all more than you really asked - you happened to catch me in a moment of transparency. To sum up: For the most part, clinical consultants in the Bay Area do pretty well, and taking a full time contractor role at a bigger company is about as safe as it gets in the consulting world. Most people are betting that the job market in our industry will continue to improve slowly over the coming year - the number of deals announced this week alone seems to support that - and in the unlikely event that your contract is not renewed after the year, your resume would probably be richer for having spent the year there getting the big company experience.

Updates to 1572 Guidance

The FDA has finally released a final FAQ, representing their 'current thinking' on 1572s.  The guidance in the form of question and answer runs for 17 pages and covers, among other things, how to fill it out, who should be listed in item #6, whether it is required to be submitted to the FDA, and under what circumstances an investigator needs to sign a new one.  Makes for surprisingly interesting reading. 

In this FAQ the 1572 is describes as having two purposes: one) to provide the sponsor with information about the investigator's qualifications and the suitability of the site for clinical trial purposes, and two) tho inform the investigator of his/her obligations and to obtain the investigator's commitment to discharge those obligations according to the regulations.  This clearly defines the document as a two-way communication tool in addition to a statement of undertaking.  The parties involved in the communication flow are the sponsor and the investigator.  Notice that the FDA is not among those sharing in this conversation.  The guidance makes it clear that sponsors are not required to submit the 1572 to the IND, although it acknowledges that most sponsors do because it is a convenient collection tool for all the information that sponsors must submit to the FDA under 21 CFR 312.23(a)(6)(iii)(b).  This is a small but potentially important distinction:  the 1572 itself is not required to be submitted, just the information contained.  A sponsor could submit that information on a separate sheet of paper and be fully in compliance.  Most regulatory folks both of sponsors and CROs have always insisted that the 1572 itself must be submitted, yet I never found a regulations supporting the policy.  It's nice to know what the requirement actually is.

Study Coordinators Now Should be Listed Routinely

Former FDAer and blogger Carl Anderson has an excellent run-down on one of the other new provisions of the guidance, namely that study coordinators should now be listed on the 1572:

“Generally, a research coordinator has a greater role in performing critical study functions and making direct and significant contributions to the study data. For example, a research coordinator often recruits subjects, collects and evaluates study data, and maintains study records. Therefore, the research coordinator should usually be listed in Section #6 of the 1572.”

This represents a major shift from the draft 1572 guidance dated July 2008, where it was recommended that study coordinators be listed if performing "critical study functions".   The change appears to acknowledge not only that study coordinators play a consistently critical role in study conduct, but also that they take a significant role in recruiting subjects.

Notice also the non-committal use of words like "should" and "generally", but don't be mistaken:  The FDA considers their guidances and FAQ's to be a close to regulation as you can get without going through the full process, so as Carl says, might be a good idea to update your 1572s to include study coordinators.

Sign It Once and Done

 
However after you get all your 1572s updated to reflect this guidance, the FDA says you shouldn't be revising them and having the investigator re-sign them any time something changes during a study, like new sub-investigators or a change in lab.  The guidance says that 1572 needs to be completed and signed by the principal investigator on only two occasions:  when participating in a new protocol under the IND or when he is being added to an existing protocol under an IND (question 7, page 6).  One hopes that this will cut down on some of the paper chase that goes on throughout long studies when people think they have to update the 1572 every time some item on it changes.  The FDA says we can simply include these changes during routine informational updates to the IND.

Use of Foreign Investigators
 
The FAQ also has a lot of guidance on the requirements of foreign investigators vis-a-vis the 1572, use of foreign data in support of submissions, foreign investigators obligations with respect to local versus US laws, and so one.  I did not know for example that multinational studies may include domestic sites under the IND and foreign sites not under the IND.  In that case the non-US investigators would not be required to sign the 1572, which is sometimes a sticking point with them as they don't wish to be obligated to US law, and the sponsor could use similar rather than exactly identical protocols to allow for differences in medical practice yet still result in pool-able data.  If this is a change it is a good one.

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How about a photo?   Here is one from a recent project management workshop that we led in Bombay.

It was mango season.

Partnerships with CROs Wrap-up

Day 2 of the Partnerships meeting in Orlando is over and while there is a day 3 tomorrow, I go home in the morning.  I was lucky enough to be on two panels discussing clinical trials in emerging markets.  Here are my highlights.

Day 1 - The morning was all pre-conference workshops so the mass of conference attendees were not evident yet.  My panel of 4 experts on the emerging regions - Mark Lanfear, Julie Margules, Nagaraja Srivatsan and me - gave a 4 hour workshop in the morning with maybe 45 people in attendance, many of whom stayed for the whole 4 hour period.  We divided up the world by regions and shared some of our experiences.  Good discussion ensued.  The session was blogged by Keith Russell, link here.  Lunch was a meeting of the Partnerships Emerging Markets Advisory Board.

In the afternoon there were some additional sessions of contracts, RFPs, and phase 1 study design concerns, followed by the keynote speaker Ethan Zohn and a reception in the exhibit hall, lots of networking.

Day 2 - The keynote speakers were Dr Jack Dean, chairman of Partnerships and then Sen. Tom Daschle who gave an excellent talk about the policy points of Health Care Reform.  He summarizes the debate in language refreshingly devoid of political heat )although I may not be unbiased as I supported the need for health care and insurance reform and thought the resulting law does not go far as it should).  He said the key points of the debate were/are: 1. the role of government; 2. the complexity of a $2.5 trillion problem; and 3. the size and nature of the pie - how big will it be, and how big will be the slice that goes to each party? Daschle then described the solution - or at least as defined by the new law - as threefold:  insurance reform, payment reform and access reform.  Of the three, the insurance component has the most detail in the new law, phasing in a series of reforms in two year increments until 2018.  Many of the most needed elements come in this year: no exclusions for pre-existing conditions in children, no recisions, no lifetime or annual limits, a small business tax credit, and rebates for seniors caught in the Rx drug gap in Medicare.  Payment and delivery reforms have less detail, but they are intended to shift the reward from volume to value, incentivize wellness, end fee for service, encourage electronic medical records (1 out of every $5 spent in health care goes to administration, paper records), encourage the use of best practices and evidence based medicine.

In the afternoon I attended a talk by Michael Marcarelli of the FDA.  He was refreshingly engaging and disarming about the business of compliance monitoring and reminded us all about the sponsor's responsibility to provide oversight for and service providers, including providing training for investigators and CROs.  He made an odd anachronistic comment when answering a question near the end when he noted with apparent surprise that so many site monitors these days do not have medical degrees, and 'sometimes they (sponsors) even send Gal Friday to monitor'.  I don't know where he has been all this time, but the industry realized literally decades ago that CRAs/monitors need not be medically qualified and even then most monitors in this country were nurses, never doctors.  And the 'Gal Friday' comment was plain offensive.

Finally it was our turn again and this time my two colleagues - Larry Fiori and Graciela Racaro - and I shared a relatively brief 45 minutes sharing what are the different considerations when doing studies in the global space, particularly the newer countries.  This session was blogged by Foreign Exchange Translations, here.

Questions

A former GCP student sent me this question today:  "Can you tell me if it is OK for a principal investigator to have his signature Xeroxed onto the ICF for the subject to sign?  This doesn’t seem appropriate to me, but I am having trouble finding anything that says otherwise.  Also, can they sign the ICF in advance of the subject signature, or should it always be after the subject consents to be in the study."

Every class term starts with my passionate admonishment that GCP is more than just knowing the rules, in fact knowing the rules is only a small part of the task.  To understand the rules, we have to think through why those rules exist.  Reading this students' question gave me an unsettling feeling that I am not being very effective at getting this point across.

Whether there is or is not a regulation about pre-signing informed consent forms, whether in ink or by photocopying, stamping, or smoke signals, is entirely beside the point.  The point is not the signature at all.   The point is what the signature represents.  (*Extra credit: is the investigator's signature even required under US regulations?)  My students have all been taught that the signature represents that the investigator's obligations to the patient with respect to the nature of the study, risks and discomforts, alternative treatments, right to withdraw and all the other elements of consent have been met.  Therefore, of course it is unacceptable to pre-sign the form, Xerox a signature onto the form or whatever else this investigator has thought up.



*Answer: No, only the patient's (21CFR 50.27(a)). Under ICH guidelines the consent should be signed by the patient and by the person who conducted the informed consent discussion (ICH E6 4.8.8).