I am thrilled to have a guest commentary this week on Carl Anderson's wonderful GXP Perspectives blog on recent changes in the clinical trials landscape in India. New rules and guidances emerging in recent months are all pointing - I believe - to an even stronger clinical trials enterprise in a country whose credentials are already very good. Please go on over to Carl's blog and take a look, make a comment. I'd love to get your thoughts.
Thanks very much indeed to Carl for his support.
Showing posts with label globalization of clinical trials. Show all posts
Showing posts with label globalization of clinical trials. Show all posts
Monday, September 26, 2011
Saturday, February 19, 2011
Upcoming Clinical Research Conferences & Events
In about 10 days I will be in San Diego for the first Ethics in Clinical Trials conference.
Current deals (I think these are still good - call 720-212-0440):
· 4 for 3: Send 4 delegates for the price of 3
· 10% off: Mention booking code leoE11
· Free Pre-Conference Workshop: preE11 (Led by me, a discussion of emerging region clinical trial ethics)
Call: 720-212-0440 or click www.ethicsintrials.com.
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Later in March I will be at Partnerships in Clinical Trials in Phoenix - March 30-April 1. I am chairing a market insight round table discussion on Strategies for Indian Clinical Trials on Thursday Mar 31, at 11:00 AM. Click here to register, or here for pricing.
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Finally, I will be in a panel discussion at MAGI's Clinical Research Conference in Philadelphia, May 22-25.
I have attended and presented at the western edition of this conference a couple of years running; this will be the first time I travel east for MAGI. I am delighted to join again with Joan Chambers of CenterWatch, Nye Pelton of Eli Lilly and Marlene Llopiz of Venn Life Sciences to discuss the current state of globalization of clinical trials.
According to the conference organizers, two-thirds of attendees will have 5+ years of experience. About 48% of attendees will be from sites, 27% from sponsors, and 25% from CROs and other service providers.
The conference website is here. A friend-of-speaker discount can save you $100 - code Q367.
The conference website is here. A friend-of-speaker discount can save you $100 - code Q367.
Click here to register. Enter the above discount code when prompted. (Does not apply retroactively or to already-reduced group rates.)
Wednesday, February 9, 2011
Offshoring Science
The current issue of IRB: Ethics and Human Research from The Hastings Center has a review of a book I wish I had written, entitled When Experiments Travel: Clinical Trials and the Global Search for Human Subjects, by Adriana Petryna. Petryna's profile page lists her as an anthropology professor at the University of Pennsylvania.
The review by Alex John London, professor of philosophy at Carnegie Mellon takes us through Petryna's review of the rise of globalization of clinical trials and discussion of the both the dangers and promise of researchers looking offshore to find trial subjects. Both London and Petryna point out that because of the power of clinical trials to shape opinions and behaviors of both patients and physicians, not to mention regulators and political forces, researchers must be all the more careful not to place clinical trials of minimally effective experimental remedies into host populations that lack access to the best proven care (to quote the Declaration of Helsinki) or to use willing and unwitting patients to generate information that may have little relevance to the planned consumers of a therapy that will not be made available to the host population.
London seems to derive from his reading something we often talk about in discussion of research ethics, or the lack thereof; namely the highly rare occurrence of one individual intentionally setting out to commit ethically problematic behavior. Far more commonly, ethical difficulties are the result of a cascade of poor decisions, delegations and skipped steps. Just as airplane crashes are most commonly the result of an accumulation of errors rather than one failed part or decision, so too with researchers and their ethical behaviors.
The IRB publication is available with a paid subscription, but Hastings have made this review available for free on their website, here. You may have to create an account to see the whole thing. It's worth it.
The review by Alex John London, professor of philosophy at Carnegie Mellon takes us through Petryna's review of the rise of globalization of clinical trials and discussion of the both the dangers and promise of researchers looking offshore to find trial subjects. Both London and Petryna point out that because of the power of clinical trials to shape opinions and behaviors of both patients and physicians, not to mention regulators and political forces, researchers must be all the more careful not to place clinical trials of minimally effective experimental remedies into host populations that lack access to the best proven care (to quote the Declaration of Helsinki) or to use willing and unwitting patients to generate information that may have little relevance to the planned consumers of a therapy that will not be made available to the host population.
London seems to derive from his reading something we often talk about in discussion of research ethics, or the lack thereof; namely the highly rare occurrence of one individual intentionally setting out to commit ethically problematic behavior. Far more commonly, ethical difficulties are the result of a cascade of poor decisions, delegations and skipped steps. Just as airplane crashes are most commonly the result of an accumulation of errors rather than one failed part or decision, so too with researchers and their ethical behaviors.
The IRB publication is available with a paid subscription, but Hastings have made this review available for free on their website, here. You may have to create an account to see the whole thing. It's worth it.
Tuesday, December 21, 2010
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.
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.
Wednesday, November 17, 2010
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
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.
photo credit: J. Mardell, 2010
Tuesday, November 9, 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.
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.
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.
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