Patient Participation in Clinical Trials: Is There a Country Difference?

In the December 2010 issue of PLoS One, a diverse group of authors from Brazil, Singapore, India and the US published a paper entitled:  So Different, yet So Similar: Meta-Analysis and Policy Modeling of Willingness to Participate in Clinical Trials among Brazilians and Indians.  Their objective was to conduct a systematic review and meta analysis (SRMA) of the literature to determine a model for predicting willingness of Brazilian patients to participate in clinical trials,and then compare the findings regarding Indian patients' willingness to participate in clinical trials.  The results if validated could be useful for sponsors and CROs planning studies to avoid wasting time and money in the wrong country and to better design protections for vulnerable patients.

The findings are based on a rather small sample of only five papers, narrowed down via various factors from 28119 (that's the systematic review part), and the authors grouped their results into two broad groups: factors favoring participation in clinical trials and factors presenting a barrier to that same end.  Interestingly, and again based on a relatively small sample, the researchers found that the most commonly cited reason for participating in clinical trials among Brazilian patients was altruism, at 55%.  Personal health benefits (30%), convenience (11%), and monetary reimbursement (6%) completed the list of favoring factors.  The barrier factors amongst Brazilian patients were: fear of adverse events (12%), mistrust (6%),  lack of knowledge (4%) and inconvenience (2%). 

By modeling this information to a previous systematic review of literature pertaining to Indian patients, the authors discovered a significant difference in Indian patients' motivations to participate in clinical trials.  The leading factors for Indian patients were: personal health benefits (48%), altruism (43%), monetary reimbursement (31%), and trust in their physician (8%).  Convenience did not factor at all for  Indian patients according to these findings.  The factors representing barriers to participation for Indian patients were:  fear of side effects (27%), mistrust of drug companies or researchers (26%), dependency issues (19%), loss of confidentiality (17%), and inconvenience (11%).

The authors also conclude from their research that Brazilian patients are more likely to participate in clinical trials than their Indian counterparts.  I think we can also draw from this the inherent vulnerability of clinical trial participants, especially in the developing and emerging regions,and use the factors favoring and inhibiting participation to help protect and reassure patients as they come into trials.

WikiLeaks and Trovan

If you thought the WikiLeaks story had nothing for you, think again.  Today's New York Times discusses a State Department cable, made available via recent the WikiLeaks dump, alleging Pfizer's attempt to disrupt the Nigerian lawsuit following several deaths after the experimental use of Trovan in Kano in 1996.  According to the Times story, the State department accused Pfizer of hiring investigators " 'to uncover corruption links' to Nigeria’s former attorney general and apply pressure to drop lawsuits against the company."  Nigeria's former attorney general, Michael K. Aondoakaa, was quoted in the piece saying he knew nothing of any Pfizer attempt to investigate him. Pfizer denied the allegations as "simply preposterous".  This is just the latest in the continuing saga of Trovan in Nigeria, which we have talked about here and here.

Happy Thanksgiving!

To all my US readers, as well as to those who have to work tomorrow, Happy Thanksgiving!  Enjoy the holiday and try not to overeat.

Has Clinical Trial Globalization Run Its Course?

A few weeks ago I had the good fortune to participate in a very interesting panel on just that topic at MAGI's Clinical Research Conference in San Francisco.  The session was chaired by Joan Chambers, COO of CenterWatch, and my panel mates were Kamran Ansari of Sanofi-Aventis and Nye Pelton of Eli Lilly.  I jumped at the chance to be on this panel because I have noticed that the recent, breathless you-heard-it-here-first pronouncements coming out of the CRO industry hearkening a great tidal wave of clinical studies to places like India, South America, Russia and Central European countries have not quite panned out.  The studies are still going to those places but not exactly in the free-for-all we were led to expect.  Does this signal that globalization has peaked, and if not, what adjustments should we make in our expectations, especially those of us with a strong international expertise component in our business models?

My view is that we are experiencing a pause in the marketplace, if not quite a correction, and we will start to see increased movement again quite soon.  I think the pause occurred for a couple of reasons: one) performance did not quite measure up to the claims of some providers, and two) the worldwide financial meltdown took an awful lot of business with it in the form of reigned in development programs and planned studies that never got started to save precious cash.  Let's look at the first reason, since this is not an economics blog.

In the first half of the 'aughts' or the decade just ended, I attended a lot of informational meetings and conferences on emerging markets and heard many vendors explain how they had so harmonized their processes, so locked in the regulatory pathways in each country that sponsors could entrust their studies to these vendors safe in the knowledge that the conduct and resulting data would be of the highest quality and the entire experience would be as painless as if the study were being run in the US or EU.  Which is many things but painless is not one of them.  And which inevitably turns out not to be true anyway.  Sponsors experienced some significant buyer's remorse when they discovered that their project manager was not the person who came to do the bid defense; that the data, ethics, and medical practice standards could be very different in actual countries of conduct and required an experienced hand in the design phase of the protocol, not just the conduct and reporting phases; that their data were being collected many time zones away by people who the sponsor had never clapped eyes on.  Instead of finding the experience painless, many sponsors felt unease with the entire process even when the data and trial results proved to be of high quality - they didn't quite trust what they saw because they didn't know who was running the trial - there was no relationship.  Vendors who were paying attention have now retooled their presentations to highlight the relationship side of the business.

Even the FDA has got on the bandwagon of mistrust.  A recent Pink Sheet ($) dated October 4, 2010 published findings by CDER's Office of Biostatistics that showed in 13 of 16 large multinational cardiovascular outcome trials, the measured drug efficacy was lower in the US than outside.  Four drugs studied in these trials were not approved specifically because of this 'regional heterogeneity' and nine of the drugs were deemed approvable but required more data.  Anecdotally I have seen this type of regional difference myself and have always interpreted it as proof of the quality of the conduct, the high acceptability of the data.  FDA says not so fast.  Some regional differences in treatment effect may be expected, but too much can arouse concern.  The Pink Sheet report cites examples such as the extended release version of metaprolol (AstraZeneca) whose 'effect on mortality was virtually all outside the US"; AZ's ticagralor which demonstrated no effect in US patients, only exUS; and whether anti-epilepsy drugs bring an increased risk of suicidality, where studies showed that outside the US, suicidality was higher.  Bridging studies, even PK/PD or surrogate studies may be indicated to explain regional differences that are not entirely due to chance.

In discussion amongst our panel and with the attendees, it seemed that at least based on the interest in the room, globalization is not dead yet. We all agreed that training, relationship, close monitoring, realistic expectations and appropriate study design are all important factors in running successful, evaluable international clinical trials.




photo credit: J. Mardell, 2010

Conducting Clinical Research

Time to play catch up with the blogging as the year begins to wind down.  The fall term at UC Santa Cruz will finish next week and I have no more conferences booked till January. 

A couple of weeks ago I attended and presented at MAGI West Conference on Clinical Research in San Francisco.  The event was neatly sandwiched in between the end of baseball pennant series' and the World Series, in which my beloved San Francisco Giants prevailed for the first time in, well, my whole life.  San Francisco was a very orange place to be during these days, and as a lifelong baseball fan left heartbroken by my team twice before in my adult life, it was a glorious time to be in the city. 

But this blog is not about baseball.  The MAGI conference was well attended by over 500 people, many more than had attended the same event last year in San Diego (on the last day of the baseball 2009 regular season, in case anyone is keeping track).  MAGI (Model Agreements and Guidelines International) so far is offered on either coast - in the east in spring and the west in the fall - and I think it is rapidly becoming one of the must-attend meetings on the yearly calendar for clinical research professionals, especially as the scope of the conference gradually expands from its origins in contracts and agreements to its current goal of "establishing best practices for clinical research operations, business and regulatory compliance".  The quality of speakers that I heard was uniformly quite high with little variation, although a couple stood out in both directions.  As the conference becomes larger it is also becoming an important networking opportunity and my LinkedIn connections have expanded significantly as a result of the acquaintances I made and renewed during the two days I attended.

One of the people I reconnected with in San Francisco is Dr Judy Stone of Maryland, the author of "Conducting Clinical Research", a newly revised quite complete how-to guide primarily written for investigators and would-be investigators to help them understand their role in the clinical research enterprise, particularly as relates to pharmaceutical industry-sponsored research, which is ultimately for profit.  Dr Stone has done her homework and produced an excellent reference that, while geared toward investigators, also offers new insights to the sponsor and CRO sides of the industry for those who might have a look.  It is always a good idea to remember to see things from the investigator's perspective, and Dr Stone has done this very well.  I plan to recommend this volume to my GCP students as adjunct reading material starting in the next term.

At the conference I was fortunate to participate on a panel entitled "Are Sponsors Re-evaluating Globalization of Clinical Sites?", moderated by Joan Chambers of Centerwatch.  In my next post I will review some of the key points of the discussion with the panel and audience. 

I close this post with the acknowledgement that our world became a great deal poorer last week when our friend Kate Allen died of gastric cancer.  She was 44.  She was a good teammate, colleague and friend, and she left many friends and loved ones behind who will miss her for the rest for our lives.

Guatlemalan Syphilis Trials and the Nuremburg Code

The New York Times has a piece this week revealing that “from 1946 to 1948, American public health doctors deliberately infected nearly 700 Gautemalans – prison inmates, mental patients and soldiers – with venereal diseases in what was meant as an effort to test the effectiveness of penicillin.”

Susan M. Reverby is a professor at Wellesley College and a medical historian who has previously written two books on the Tuskegee syphilis trial, discovered records of these experiments in the archives of the University of Pittsburgh as she was preparing a research paper. The archives also revealed that NIH funds were used to pay syphilis-infected prostitutes to sleep with prisoners in order to infect them. If that method didn’t work, patients were infected by experimenters pouring live bacteria over abrasions on their scraped up body parts or injected directly into the spine.

The connection to Tuskegee is not accidental. The Guatemalan experiments were led by one John C. Cutler,  a public health service doctor who was to become instrumental in the Tuskegee experiments later on, and it was his unpublished Guatemala work that Reverby discovered at Pitt. Reverby told the Times that she had previously presented her findings at a conference last January but received no reaction. In June she submitted a manuscript for a future issue of the Journal of Policy History to Dr David J. Sencer , former director of the CDC (a body that has its own not completely benign role in the Tuskegee affair), and he requested a government investigation.

All of this was going on at the same time military and civilian lawyers at Nuremburg were mounting a vigorous prosecution of Nazi physicians in the Doctors’ Trial following WWII. From this prosecution came the Nuremburg Code from whose appearance many ethicists date the modern era of human subjects protection, a code which included such protections as voluntary consent, a favorable risk/benefit analysis, avoidance of needless suffering, appropriate prior animal data, the right to withdraw, and so on. US public health doctors were conducting VD trials on presumably unconsented (or at least not fully informed) subjects at the same time physicians were being hanged in Germany for doing the same things. The theme connecting these events is this: lack of respect for person, the unwillingness of the experimenters to see research subjects as full human beings deserving of protection and respect.

In the wake of these revelations, Secretary of State Clinton and HHS Secretary Sebelius have issued an apology to Guatemalans, the subjects and their descendents, and of course it is not their fault. We do not need to waste time looking for conspiracies in the US government. FDA regulations, the Common Rule, the Declaration of Helsinki and ICH and WHO-CIOMS guidelines for GCP are all designed to protect future human subjects. Our job is to make sure that we educate our successors so that things like this never happen again.

Should FDA split safety ops from CDER?

This is a topic that comes up early in my GCP class at UC Santa Cruz Extension, when we do an overview of the FDA's operations and PDUFA as they pertain to good clinical practice.  PDUFA has over the years enabled a a more efficient and predictable pathway through the US regulatory review process.  Improvements are not without cost, and the consequences here have been felt on the continuing review of the safety of marketed medicines as budget has shifted to meet the Congressionally mandated trigger for user fees, and one option long under study has been to move safety evaluations altogether away from the evaluation of new drugs.


Bloomberg today has looked at the data since 1995 (PDUFA was first enacted in 1992) and reports that over half of the 21 drugs approved since 1995 have since been withdrawn from the market behind cardiovascular problems.  Armed with these findings, Sen Chuck Grassley (R-Iowa) is developing a bill with Rep. Rosa DeLauro (D-CT) to create a new Office of Surveillance and Epidemiology whose function - and one presumes budget - would be completely separate from CDER and its budgetary constraints, and its heavy reliance on voluntary post-marketing adverse event reporting.  FiercePharma has it all here, along with an interesting link to a story about Sen Grassley's plans to move from the Senate Finance Committee to Judicial.  You read it here second.


Next week I will be attending and speaking at this meeting, Managing Relationships with CROs in London, and then a couple of days off.  

FDA's HSP/BIMO Progress Report

The FDA has released a progress report on its Human Subjects Protection/Bioresearch Monitoring Initiative (HSP/BIMO).  In the 18 months since launch several new regulations and guidelines have been produced, including:

• IRB registration;
• Expanded access to investigational drugs;
• A new informed consent essential element notifying subjects of study registry on the clinicaltrials.gov system;
• The final guidance on 1572s;
• New guidance on investigator responsibilities;

And a whole bunch more.  Included in the report is an update from the FDA/Duke University Clinical Trials Transformation Initiative (CTTI), which includes among many other things a joint initiative between FDA and EMA for good clinical practice.  The EMA/FDA GCP terms of engagement and procedures document is here.  The HSP/BIMO report is here.

FDA Limits Action Against HIV Investigator

A story linked via FierceBioTech today from an article published last week in the Chicago Tribune describes the apparently light touch the FDA is using to discipline an investigator whose clinic allegedly submitted fictitious data in a clinical drug trial.  Standard procedure in such cases is usually either disqualification from running clinical trials altogether or restriction of the number of trials an investigator may conduct or the number of patients they may enroll.  This investigator, whose writings about HIV are easily searchable on the Web, apparently escaped all such restrictions and instead is allowed to continue clincal trial operations under the supervision of an outside medical monitor for the next three years and is required to submit annual reports to the FDA in that same three year period.  This seemingly light slap runs counter to the message being sent to drug manufacturers themselves for whom the agency is stepping up its oversight with warning letters, product recalls and threats of prosecution, according to the Fierce story. 

Switching gears entirely, here is a link to the OHRP's 2010 International Compilation of Human Research Protections.  This is an absolutely invaluable resource covering the key organizations, legislation, regulation and guidelines pertaining to human subjects protection of 96 countries, updated every year with clickable links.  Every clinical research professional planning studies anywhere in the world including the emerging regions should make this document their first stop. 

Roche Jobs Shift to China

As a former Roche employee (and holder of a pension) my eye is always drawn to stories about changes at that company.  Last week they announced a major cost cutting effort in the US and Europe, letting slip an internal memo naming the employees responsible for each sector.  This week they are announcing a hiring boon in China, increasing headcount there by as many as 750 jobs.  This appears to be the sharp end of the stick in China that we have been watching for, as the Chinese government invests in its drug development capacity and more large sponsors move in to establish operations.  The Fierce article notes that Eli Lilly announced thousands of layoffs last year while staffing up in China.  I think this puts India under some pressure, as clinical trial application approval times there have slipped into 120 days and more, a not very welcoming gesture to sponsors interested in running clinical trials there and have the means to ensure patient safety and ethical conduct.

FDA's Marketing Crackdown

There has been a lot of news about the FDA cracking down on drug makers advertising direct to consumers, which is either a) poor ethical behavior or b) an indispensable way to educate the marketplace, depending on your biases.  I tend to lean toward the former.  Anyway FiercePharma has been following this issue closely, and has an item here worth checking out.

I read this blog from Steven Grossman called FDA Matters, which I found via GxP Perspectives.  The whole FDA is covered not just drugs, so I pick and choose the articles within my wheelhouse. Take a look.

I have a few more speaking engagements coming this year:  Managing CRO Partnerships in London October 4-5, and MAGI West in San Francisco October 24-27.  See the sidebar for links and details.

Also I will be moderating a panel at Astia's Silicon Valley Doing It Right session in San Francisco November 5.  Astia is a program that provides resources and training for women entrepreneurs in life sciences, technology and clean tech.

The fall term starts at UC Santa Cruz extension today; 10 weeks of GCP class.  It's not too late to sign up.

We've Hit the Big Time!

Two Decades just got listed on this posting at GxP Perspectives as a blog "well worth checking out".  Thanks Carl!

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).

New Year, New Challenges

The new year has hit the ground running hard and many colleagues are just trying to hang on. The good news is that though we are still in the midst of some hard times, we are starting to see an upturn in movement of money, new clinical programs under development, and jobs. Enrollment is up in the UC Santa Cruz certificate programs where I have taught for the last 10 years and in honer of the winter term just getting underway, I posted a picture from my most recent trip to India of a woman walking her children to the school bus in Bangalore.

The conference season is in full swing. I just came back from the Indian Society for Clinical Research's excellent 3rd annual national conference at the Hotel Leela Kempinski in Bangalore. Attended by 500 participants from all over India and beyond, the conference featured many of the most influential people in the Indian clinical research field as well as many young CRAs and project managers, and it was a fantastic opportunity to listen and learn from the people who know the region best.

This week I will be attending and presenting at Outsourcing in Clinical Trials West Coast in San Francisco, on the topic of Offshoring to Emerging Countries: Navigating Uncertain Waters. I gave a similar talk last week as an advance for the Partnerships in Clinical Trials event to be held in Orlando in April. I'm told a podcast of last week's talk is forthcoming and I will make it available to anyone who contacts me for it. This week I am also presenting in a webinar entitled Biotech and the Global Marketplace for the US Commercial Service. My task is to discuss clinical trials in emerging markets and opportunities for US biotech companies to enter into co-development projects with sister companies in these regions.

My partner and I were recently featured in a blog post over at goBalto.com about the Indian clinical trial market- see it here.

I receive regular updates from Audrey Erbes, who is a faculty colleague of mine at UC Santa Cruz extension and teaches in the biosciences certificate program. I took her 2 day course on business development and highly recommend it. Here is her excellent blog where she freely shares huge amounts of information from her network including job postings with students and colleagues alike. Highly worth subscribing to in your reader.

2010 represents my 30th year in the clinical research field. Next year I will have to rename my blog to '3 Decades, Full Stop'.