THE TRIALIST

End of an era for Pap smears?

noreply@blogger.com (The Clinical Trials Wiki team) — Mon, 06 Apr 2009 21:54:00 +0000

Read the surprising results of a large-scale cervical cancer trial conducted in India. The New York Times has the story here. Could this DNA-based assay for HPV spell the end of annual Pap smears in developed countries, and of lower quality cervical cancer tests in resource-poor settings? If so, it would come as a welcome relief to millions of women, and require a dramatic revision of cancer screening guidelines. Here's media from the article:

Wide enthusiasm is developing for the new DNA test among gynecologists, patients, and public health workers. According to Mark Schiffman of the National Cancer Institute who wrote the NEJM editorial accompanying the article, "The implications of the findings of this trial are immediate and global. International experts in cervical cancer prevention should now adopt HPV testing."

FDA staffers vent to President

noreply@blogger.com (The Clinical Trials Wiki team) — Sun, 05 Apr 2009 22:07:00 +0000

Check out this story about whistle blowing from inside FDA. Thanks to a tip from PharmaGossip, we've learned of a letter sent by FDA insiders to President Obama on April 2, 2009. You can read the full text of the letter here. The letter was well timed to coincide with the appointment of the FDA's new commisioner, Dr. Margaret Hamburg, who many hope will inaugurate a new era of transparency and accountability at the agency.

The FDA staffers complain of a growing sense of frustration with the 'arbitrary and capricious' decision making at the upper echelons of FDA:

The latest example of wrongdoing was reported on March 23, 2009 from a Federal District Court Judge who ruled that FDA’s decision on the Plan B drug was “arbitrary and capricious because they were not the result of reasoned and good faith agency decision-making.” FDA’s top leaders at the Center for Drug Evaluation and Research (CDER) testified that they “didn’t have a choice, and . . . [weren’t] sure that [they] would be allowed to remain [in their positions if they] didn’t agree” to ignore the science and the law. To the contrary, they should be removed from their positions of authority precisely because they didn’t follow the science and the law. The judge further ruled that there was “unrebutted evidence that the FDA’s [decision] stemmed from political pressure rather than permissible health and safety concerns.” The “improper political influence” and the many “departures from its own policies” reveal that such FDA officials are incapable of ensuring integrity
and science at FDA.

They go on to report concern with the agency's culture of wrongdoing and coverup, saying 'FDA is fundamentally broken':

On January 7, 2009, FDA physicians and scientists wrote to Mr. John Podesta: “Through this letter and your action, we hope that future FDA employees will not experience the same frustration and anxiety that we have experienced for more than a year at the hands of FDA managers because we are committed to public integrity and were willing to speak out. Currently, there is an atmosphere at FDA in which the honest employee fears the dishonest employee, and not the other way around. Disturbingly, the atmosphere does not yet exist at FDA where honest employees committed to integrity and the FDA mission can act without fear of reprisal. … America urgently needs change at FDA because FDA is fundamentally broken, failing to fulfill its mission, and because re- establishing a proper and effectively functioning FDA is vital to the physical and economic health of the nation.”

It's unclear from my vantage point how many of these accusations are merited. But it's certain that at least some FDA employees (names blacked out in the letter, but judging from the size of the text block, appears to be 5-10 individuals) have honest concerns about the agency's current culture and future directions. We're hopeful that the coming weeks will shed more evidence about the mistakes that have been made, and how Dr. Hamburg intends to reinvent FDA with a commitment to institutional integrity.

Radio silence explained

noreply@blogger.com (The Clinical Trials Wiki team) — Sun, 05 Apr 2009 21:33:00 +0000

You may have noticed sparse posting on this blog after announcing our newest Board of Directors additions in March.

Yet we've been keeping busy behind the scenes, as we've sharpened our focus on grant-writing and securing stable financing for our project. Here's a recap of some of our achievements last week:

We submitted our first grant application to Changemakers.net (an initiative of Ashokha Foundation) and have several more applications in process. In the spirit of full transparency, you can read our grant application in its entirety here.
We welcomed Umer Raffat, M.P.H., to Clinical Trials Wiki as our new V.P. of Finance/Strategy.
We are beginning an architectural overhaul of the site, expanding our database of publicly accessible clinical trials, and centering our content display and discussion forums around scientific publications from the clinical trial literature.

As you know, we're continuing work on this site alongside our day-to-day lives. Last week I started a rotation at the Brigham's Levine Cardiac Unit, which will keep me busy through the end of April, and am spending my weekends hunting for apartments in Murray Hill. While still mysteriously finding time to write and edit our grants, Brice is traveling France on what promises to be a life-changing trip. And, inspiring the envy of overachieving multi-taskers everywhere, Gaurav is working behind the curtain on technical development after his day job at a venture capital firm.

Please continue to send us your questions or feedback about our ongoing work on the site.

James Muller, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

noreply@blogger.com (The Clinical Trials Wiki team) — Tue, 24 Mar 2009 00:54:00 +0000

We are honored to welcome Dr. James Muller, renowned cardiologist and one of three co-founders of an organization that won the 1985 Nobel Peace Prize, to our Board of Directors. His bio follows:

James E. Muller, M.D., was one of three American Co-founders of the International Physicians for the Prevention of Nuclear War (IPPNW) the organization awarded the 1985 Nobel Peace Prize.

Dr. Muller currently serves as CEO of InfraReDx, Inc, a company that has developed a near-infrared spectroscopy catheter for the identification of lipid-rich and presumably vulnerable coronary artery plaques.

Dr. Muller formerly served as a Professor of Medicine at the Harvard Medical School where he conducted research for over 25 years on the causes of heart attacks. In 1994, he introduced the term "vulnerable plaque" to describe those plaques likely to disrupt and cause disease onset. He co-founded InfraReDx in 1998 after a detailed search to find the optimal technology to identify lipid-rich coronary artery plaques.

Jeff Drazen, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

noreply@blogger.com (The Clinical Trials Wiki team) — Mon, 16 Mar 2009 13:18:00 +0000

Dr. Drazen has been a mentor and friend to us for many years in the H.S.T. program at Harvard Medical School.

We extend a warm welcome to Dr. Drazen as he joins our Board of Directors today. His full bio follows:

A specialist in pulmonology, Jeffrey M. Drazen, M.D., maintains an active research program. Dr. Drazen has published more than 300 articles on topics such as lung physiology and the mechanisms involved in asthma. In 1999, he delivered the Amberson Lecture, the major research address at the annual meeting of the American Thoracic Society. In 2000, he received the Chadwick Medal from the Massachusetts Thoracic Society for his contributions to the study of lung disease.

Dr. Drazen is the Distinguished Parker B. Francis Professor of Medicine at Harvard Medical School, professor of physiology at the Harvard School of Public Health, and senior physician at the Brigham and Women’s Hospital. In 2003, he was elected as a member of the Institute of Medicine. Dr. Drazen has served on numerous committees for the National Institutes of Health: the Respiratory and Applied Physiology Study Section; the Lung Biology and Pathology Study Section; the Pulmonary Disease Advisory Council; and the National Heart, Lung, and Blood Institute Advisory Council. He currently serves as the co-chair of the Institute of Medicine Drug Forum and is a member of the advisory group to the World Health Organization International Clinical Trials Registration Platform.

Dr. Drazen joined the New England Journal of Medicine as editor-in-chief in July 2000. At the Journal, Dr. Drazen’s responsibilities include oversight of all editorial content and policies. His editorial background includes service as an associate editor or editorial board member for the Journal of Clinical Investigation, the American Journal of Respiratory Cell and Molecular Biology, and the American Journal of Medicine.

Dr. Drazen earned his bachelor’s degree and graduated summa cum laude from Tufts University. He received his medical degree from Harvard Medical School and completed his internship and residency at Peter Bent Brigham Hospital in Boston. Dr. Drazen received honorary degrees from the University of Ferrara, Italy, and the National and Kapodistrian University of Athens, Greece.

A native of Missouri, Dr. Drazen lives with his wife in Winchester, Massachusetts. They are the parents of two grown sons.

Warner Slack, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

noreply@blogger.com (The Clinical Trials Wiki team) — Thu, 12 Mar 2009 01:51:00 +0000

We are delighted to welcome a second distinguished clinician to our Board of Directors today, Warner Slack, M.D.

Dr. Slack brings us over 35 years of experience in health information technology. He is currently co-president of the Center for Clinical Computing and, during his medical training, helped develop one of the world's first electronic health record (EHR) systems. His full bio follows:

Dr. Slack received his bachelor's degree from Princeton University, his medical degree from Columbia University's Columbia University's College of Physicians and Surgeons, and his residency training in neurology at the University of Wisconsin. Over the past 35 years he has focused his research on the use of computers to improve communication in medicine and to empower both doctors and patients for better health care. His early work in computer-based medical interviewing at the University of Wisconsin led to the first study of patient-computer dialogue.

Over the years, he has established new computer-based approaches to the medical interview, and developed and studied programs that provide direct assistance to the patient in the management of common, important medical and psychological problems. He was an early advocate of the patient's right to participate in decisions about diagnosis and treatment.

Dr. Slack and his colleagues at the Center for Clinical Computing (CCC) and the Harvard Medical School, have developed, implemented, and studied an integrated, hospital-wide clinical computing system (the CCC system) which is used in patient care at Boston's Beth Israel Deaconess Medical Center and Brigham and Women's Hospital. Distinguishing features of the CCC system are the unparalleled intensity and extensiveness of its use by clinicians in the care of their patients and the substantial financial benefits that have been realized in conjunction with its use.

Dr. Slack is Professor of Medicine at Harvard Medical School and, with Dr. Howard L. Bleich, co-president, of the Center for Clinical Computing and co-director of the Division of Clinical Computing, Department of Medicine, Beth Israel Deaconess Medical Center.

Among his recent publications, Dr. Slack is the author of Cybermedicine: How Computing Empowers Doctors and Patients for Better Health Care (revised and updated edition, San Francisco: Jossey-Bass, 2001).

Edward Hundert, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

noreply@blogger.com (The Clinical Trials Wiki team) — Thu, 12 Mar 2009 01:43:00 +0000

We are delighted to welcome Dr. Edward Hundert, M.D., former President of Case Western Reserve University, to the Clinical Trials Wiki family, and as a member of our Board of Directors. His bio is below:

Dr. Hundert is an internationally known academic leader, scholar, educator, psychiatrist, and medical ethicist. Over the past 20 years, he has served as President of Case Western Reserve University, Dean of the University of Rochester School of Medicine and Dentistry, and Associate Dean for Student Affairs at Harvard Medical School. He has held professorial appointments in psychiatry, medical ethics, cognitive science, and medical humanities, and he is a leader in developing innovative institutional affiliations and curricula both in academic medical centers and across all levels of higher education.

Dr. Hundert earned his bachelor’s degree in mathematics and the history of science and medicine, summa cum laude, from Yale University, where he received Yale’s Chittenden Prize “to the graduating senior with highest standing in mathematics or the natural sciences.” He attended Oxford University as a Marshall Scholar, receiving the Batterby Prize from Hertford College for “highest first class honours in philosophy, politics and economics.” Four years later he earned the M.D. from Harvard Medical School, receiving the Sanger Prize for “excellence in psychiatric research.” He completed his psychiatric residency at McLean Hospital, a Harvard affiliate, where he served as chief resident. He has received numerous teaching, mentoring, and diversity awards, and for six consecutive years he was voted the “faculty member who did the most for the class” by Harvard Medical School graduates.

Dr. Hundert has served on many national boards, including the Association of American Universities, the American Association of Medical Colleges, and the Liaison Committee on Medical Education. He co-chaired the Institute of Medicine’s National Summit on Health Professions Education. Dr. Hundert has served as chair of the Ethics Committees of McLean Hospital and the Massachusetts Psychiatric Society, and also served as ethics column editor for the Harvard Review of Psychiatry. Dr. Hundert has written dozens of articles and chapters on a variety of topics in psychiatry, philosophy, medical ethics, and medical education, as well as two books: Philosophy, Psychiatry and Neuroscience: Three Approaches to the Mind (Oxford University Press, 1989), and Lessons from an Optical Illusion: On Nature and Nurture, Knowledge and Values (Harvard University Press, 1995).

In addition to his work in the Division of Medical Ethics, Dr. Hundert is a member of the boards of TIAA-CREF and the Rock and Roll Hall of Fame.

Two new additions to our Board of Directors

noreply@blogger.com (The Clinical Trials Wiki team) — Thu, 12 Mar 2009 01:03:00 +0000

We're pleased to announce the addition of Warner Slack, M.D., and Edward Hundert, M.D., to our Board of Directors. Both of these distinguished clinician-educators share our vision for a fully transparent, non-commercialized source of clinical trials information and opinion.

We are fortunate to count them among the Clinical Trials Wiki family.

Full bios of each new Board member will be posted shortly on this blog and our main site, ClinicalTrialsWiki.org.

Health IT: the new Apollo program?

noreply@blogger.com (The Clinical Trials Wiki team) — Wed, 11 Mar 2009 12:28:00 +0000

Yesterday, Mark Leavitt over at THCB compared the portion of Obama's "American Recovery and Reinvestment Act" dealing with electronic health records (EHR) to Kennedy's program to send a man to the moon. Sound far-fetched?

Here's the quote (full article after the jump):

I’m personally struck by the parallels to a historical event still vivid in my memory: Project Apollo, President Kennedy’s incredible national goal of achieving manned spaceflight to the moon.
Apollo cost $22B (in 1969 dollars, now worth five times that) and took 8 years to achieve the first moonwalk. NASA, a new government agency, spearheaded the effort, but the technology was developed by private sector contractors.
The health IT provisions of ARRA invest at least $35B to incentivize full EHR deployment, allowing 5-7 years to reach that goal – remarkably similar to Project Apollo. The Office of the National Coordinator (ONC) has been codified and funded to lead the effort, and just as in the case of Apollo, I expect much of the work will need to be accomplished by contractors in the private sector -- CCHIT included, of course, provided we quickly “grow up” to meet the enlarged responsibilities.

While EHR won't induce the sort of national high drama that the Apollo program did (I can see eyeballs rolling already...), Mark does have a point about the similar scale and impact of the two projects. Arguably, EHR will actually have far greater impact, through the improved patient outcomes that result from increased accessibility, consistency, and comprehensiveness of our new health records.

Yet until recently, EHR was hardly brought up in the national discourse about high-impact fixes to improve health care. James Holsinger, in all his bespectacled charm, never once mentioned the issue during his prolonged confirmation process for U.S. Surgeon General in '07.

As Mark rightly points out, the thorniest issues surround adoption of new EHR technologies -- getting a physician to give up old patterns of behavior (see NHS's initiative in England to banish white coats) may prove harder than shooting the moon.

Our new Facebook home

noreply@blogger.com (The Clinical Trials Wiki team) — Tue, 10 Mar 2009 11:54:00 +0000

Yesterday morning, I created a new Facebook group to coincide with the launch of our new website. So far it's Gaurav, myself, and 12 good friends. Brice, we think, is trapped in the bowels of the ICU and hasn't had a chance to join yet!

Here's how we describe ourselves on Facebook:

ClinicalTrialsWiki.org strives to be the most trusted source of clinical trials information online. You can search our database of analysis and opinion on over 65,000 clinical trials.

We're structured as a 100% volunteer-run, 501(c)(3) nonprofit and, as a policy, we don't accept ads or money from the pharmaceutical and medical device industries.

That's all there is to it -- no ads, no gimmicks, and no tricks up our sleeve.

The site was developed by three friends at Harvard Medical School and M.I.T.

We'd love to see you join our community!

Whew!

noreply@blogger.com (The Clinical Trials Wiki team) — Mon, 09 Mar 2009 03:50:00 +0000

I think I speak for the entire team at ClinicalTrialsWiki.org when I say that we're thrilled to have a new, far more functional site go live today. Everyone here has been working feverishly over the last 72 hours to get this work done, though it's just the beginning.

To his credit, Brice has been on call in the ICU and several times decided to get work done with us post-call instead of going to sleep. And this weekend, Gaurav heroically led our webcrawler development effort though his new fiancee flew into town for the weekend! Both of my teammates continue to inspire me with their passion for this project.

Here are a few highlights of our achievements over the last few days:

We designed and implemented a Wikibot to automate the extraction of data from ClinicalTrials.gov
We laid out a brand new format for our clinical trials 'data' page
We decided on a new logo, color scheme, and website layout
We met with friends and colleagues at HMS, the Countway medical library, and HealthMap to get feedback on our ideas and refine our thinking about the site
We've set up meetings with NEJM and FDA to discuss possible partnership and site integration

Every minute as I write this, our crawler is adding 5-10 new fully populated clinical trials to our site. Look for even more changes to come, particularly as we enhance the usability of the wiki features of the site, so that anyone on the web can edit articles and upload data files.

We're committed to being 100% transparent with you about how we develop and maintain our site. We know you might have ideas about where we should go from here, and we want to hear from you.

WikiBot is Online

noreply@blogger.com (The Clinical Trials Wiki team) — Sun, 08 Mar 2009 22:54:00 +0000

After a weekend of hacking php (and with the help of the fantastic source code of BasicBot), we've finished our first database-browsing, wiki-populating, automated bot which will populate the wiki with content and expert pages for all 65,000 trials on the clinicaltrials.gov database. The bot is chugging along diligently, and we expect to have completed the population process by mid-week.

In the future, we're planning on creating a multi-threaded bot that will speed up the process tremendously, as well as limiting updates to new or revised content from clinicaltrials.gov. For now, we're just excited that we'll soon have more content than we'll know what to do with -- ready and waiting for your discussion and analysis!

On the aesthetics front, we're continuing to modify the layout of individual content pages to make it as easy as possible to navigate the plethora of data and find the information you're looking for. As always, we'd love your feedback and suggestions.

If you're curious, you can see the trials being added in real-time by the bot on the "New Pages" list.

Version 2.0 is Live!

noreply@blogger.com (The Clinical Trials Wiki team) — Thu, 05 Mar 2009 14:22:00 +0000

ClinicalTrialsWiki.org has finally gotten a much-needed aesthetic overhall -- the first of many revisions, I am sure. It's a work in progress, so please leave your feedback.

We're also putting the final touches on an automated PHP crawler bot that will keep every trial on ClinicalTrialsWiki in sync with the ClinicalTrials.gov repository, and ensure that all of the information is up-to-date.

Things are exciting around here, and I can feel the momentum building!

Supreme Court rules on different standards for drug and device makers

noreply@blogger.com (The Clinical Trials Wiki team) — Wed, 04 Mar 2009 20:30:00 +0000

Does a patient who's undergone implantable cardioverter-defibrillator (ICD) placement, and whose ICD's electronic components have now failed -- requiring emergent device replacement -- have the right to sue the cardiac device's maker for negligence, if he was repeatedly warned by his cardiologist of the well-known risk of post-implantation electronics failure?

Device makers have long argued 'No': every device has risks, and the FDA-CDER premarket approval process is designed to weigh risk against benefit before permitting the introduction of a new device. The Supreme Court last year substantially agreed with this view in Reigel v Medtronic by ruling that successfully obtaining premarket approval from the FDA gives medical device makers (in this case, Medtronic, a manufacturer of ICDs) a strong defense against lawsuits filed in state courts because federal regulation "pre-empts" state law here.

Today, under presumably different logic, the court ruled in Wyeth v. Levine that drug makers can be sued in state courts, even when they have obtained FDA approval.

So why the discrepancy? The Wall Street Journal Health Blog reports on the issue today:

The 8-1 ruling in the medical device case, Riegel v. Medtronic, relied heavily on the “Medical Device Amendments” signed into law in 1976.
As the court wrote in Riegel:
The MDA provides that no State ‘may establish or continue in effect with respect to a device . . . any requirement’ relating to safety or effectiveness that is different from, or in addition to, federal requirements …
That language goes to the heart of preemption, the legal question at issue in both cases: Does federal regulation override state law? In the case of devices, the court found, MDA explicitly preempts state law.
But the MDA is all about devices, while the case decided today, Wyeth v. Levine, is all about drugs. The relevant drug law is the Food, Drug, and Cosmetic Act, enacted in 1930 and amended several times in the decades since then.
Amendments added in 1962 indicated “that a provision of state law would only be invalidated upon a ‘direct and positive conflict’ with the FDCA,” Justice Stevens wrote in his majority opinion in Wyeth v. Levine.
What’s more, Stevens added, “when Congress enacted an express pre-emption provision for medical devices in 1976″ — in the MDA — “it declined to enact such a provision for prescription drugs.”

The notion of pre-emption gets to the very heart of our national experiment with federalism, and makes for a fascinating legal discussion. But it's unfortunate for most Americans that this case hinged on the issue of pre-emption, rather than addressing the broader social ramifications of an increase in state and federal drug lawsuits in our already litigation-littered society.

Something just doesn't sit well with me about our asymmetric policy for dealing with device and drug companies (largely for historic reasons related to the recency of most device legislation, and the relative strength of industry lobbying groups). We've long been doing this to our detriment, I think, in the FDA's 510K process of rapidly approving "substantially equivalent" devices.

Medical device and pharmaceutical companies face enormous legal liability and financial risk in developing the innovative therapies that physicians and patients rely upon.

So there's a few reasons why I agree with the Court's original decision in Reigel v Medtronic:

First, mitigating the legal liability to device companies removes downward pressure on innovation;
Second, the tort system in our country is badly broken, with punitive damages awarded by juries in many cases exceeding the pale of reason;
Third, I'm hoping this decision will spur legislation to give FDA broader oversight and stricter controls over device development and postmarketing surveillance.

If we're answering the question of whether the companies have been negligent, and we ask -- did their actions "cause" the damages suffered, and could a "reasonable person forsee the harm" to the patient in this case? -- then I think the answer to both questions is yes.

However, drugs and devices, by virtue of their intimate relationship with our bodies, have the potential to cause immense, sometimes irreversible, harm. We can predict, and warn about the dangers of, this harm by conducting preclinical and clinical trials.

Our regulatory process should (in the ideal world) weed out those drugs or devices whose risk/benefit profile is tipped towards risk, and protect companies and physicians who adequately educate patients about that risk prior to starting treatment. Otherwise life-saving therapies would never see the light of day for fear of a class-action lawsuit.

HMS featured in NYT article today

noreply@blogger.com (The Clinical Trials Wiki team) — Tue, 03 Mar 2009 16:57:00 +0000

Today's most popular NYTimes article features Harvard Medical School's conflict-of-interest policy and ties to the pharmaceutical industry.

Read the full article here.

The team at ClinicalTrialsWiki.org is currently composed of fourth-year students at Harvard Medical School. We believe our site can go a long way towards promoting transparency and nonbias in medical education.

Kudos to the students who've been featured in the article for the work they are doing.

noreply@blogger.com (The Clinical Trials Wiki team) — Mon, 02 Mar 2009 23:19:00 +0000

Don't mix PPIs and Plavix...
How many patients are not on a PPI these days?...should they be?

A retrospective study published in JAMA this week strongly suggests that one should be careful when prescribing PPIs upon discharge of patients hospitalized for an acute coronary syndrome (ACS). When comparing the use of a PPI in patients with ACS taking clopidrogel after discharge, Michael Ho et al. found that patients taking clopidrogel and prescribed a PPI had a higher risk of death or rehospitalization for recurrent ACS than those who were taking clopidrogel alone (Adjusted odds ratio 1.25 CI[1.11-1.41]) (1). The results of this study are supported by several translational and mechanistical studies showing that the use of PPIs reduces the antithrombotic effects of clopidrogel (2), (3).

Maybe all of us future interns should follow our pharmacology professor's suggestion to place a bottle of Omeprazol pills under each patient's pillow on the wards. That way, when asked by a tired junior resident to put Mr. Jones on a PPI, we can safely say that he's already "on" it...

(1) P. Michael Ho et al. JAMA. 2009; 301(9): 937-944
(2) Gilard M. et al. J. Thromb Haemost. 2006; 4(11): 2508-2509
(3) Gilard M et al. J Am Coll Cardiol. 2008; 51 (3): 256-260

Redesign of main wiki page

noreply@blogger.com (The Clinical Trials Wiki team) — Sun, 01 Mar 2009 17:52:00 +0000

The main wiki page at ClinicalTrialsWiki.org is now much richer with content, which we'll continue to update on a daily basis. This is what it looks like on my home computer:

After hacking around with the MediaWiki source code (compliments of Matthew Burton's free help page), we've also configured a new 'expert' tab on all of our content articles (i.e., clinical trial pages). Look for expert commentary to populate these tabs in the coming weeks.

We're live at ClinicalTrialsWiki.org!

noreply@blogger.com (The Clinical Trials Wiki team) — Fri, 27 Feb 2009 22:47:00 +0000

The title says it all. Check us out at http://www.clinicaltrialswiki.org.

The wiki itself is still in prototype form, but we're working quickly to populate it with objective data from each of over 65,000 federally registered trials. Here's a screenshot:

Yesterday someone asked me how much we're getting paid for doing this. Zip. Yes, you heard it here first -- this is a 100% volunteer-run project.

We're doing it because we're frustrated at the lack of unbiased, comprehensive sources of clinical trial information and analysis. And we're optimistic that a new service like ours could bring together students, researchers, clinicians, and industry to the common cause of improving patient outcomes.

From call centers to... clinical trials

noreply@blogger.com (The Clinical Trials Wiki team) — Thu, 26 Feb 2009 08:52:00 +0000

Fascinating post at CenterWatch on the rapid growth of global outsourcing of clinical trials. I highly recommend this post in its entirety.

The study, published in Wednesday’s New England Journal of Medicine (NEJM), reports that the number of countries conducting drug testing has doubled in the past 10 years, and, in November 2007, a total of 13,521 of 24,206 investigative sites being used for studies sponsored by U.S. big pharma were international.

Kevin A. Schulman, the lead author of the NEJM article and a professor of medicine at Duke, was interviewed by NYT. It is surprising just how nascent this field is:

The Duke study has ignited furor from the halls of big pharma. They point to the success of international trials for Gardasil (the quadrivalent HPV vaccine from Merck), and the clinical importance of this vaccine for developing countries. Why, they argue, should we prevent the rest of the world from sharing the cutting-edge therapies that we enjoy here at home? The U.S. enjoys the largest and most innovative pharmaceutical industry in the world, so why not expand our global market share by exporting business worldwide?

Indeed, global outsourcing may provide ancillary benefits ("collateral rescue") to entire resource-poor communities: an executive at Millenium Pharmaceuticals recently told me that his company has invested millions of dollars directly into hospital infrastructure improvements throughout the EMEA region, simply to bring up local quality standards to meet the FDA's trial compliance guidelines.

While there's nothing inherently bad about conducting trials internationally, most criticism stems from concern that good clinical trial practices (things like informed consent, blinded controls, patient compliance and followup) are much harder to enforce abroad. It's also questionable whether data collected in one patient population (e.g., Western Saharans) can be used to justify a claim for efficacy in another (e.g., Southern Californians).

Furthermore, Phase I trials, which primarily involve healthy volunteers, will often use monetary incentives to recruit patients. The ethics of doing this in the developing world is murky at best, particularly when individual incentive structures are sharply skewed by widespread poverty, famine, or conflict. I haven't yet heard any good consensus frameworks for thinking about the ethics of risk v. benefit within the context of international trial design.

CenterWatch offers its own multi-point rebuttal of the Duke study:

The sample size is almost half of the trials listed at the time, compared to a more comprehensive analysis of clinical trials listed in August of 2007 done by Goldman Sachs.
The study’s analysis of the 20 largest drugmakers in the U.S. excludes more than 1,900 other companies developing drugs around the world.
Of the 20 countries outside the U.S. doing the most trials in August of 2007 (from the Goldman study), only four—Poland (13th), Russia (17th), Brazil (19th), and the Czech Republic (20th) could be considered emerging markets.
The percentage of clinical trials initiated overseas increased from about 13% in 1997 to about 30% in 2005. At the end of 2007, the number was just under 34%. The number of trials being conducted worldwide has gone from around 22,000 in 1997 to about 37,000 in 2007.
While the number of clinical trials initiated overseas has increased dramatically, the study overstates the share of trials overseas by more than 20 percentage points.

John Lewis of the Association of Clinical Research Organizations (ACRO) posted a lengthy (if boilerplate) comment after the post that's at least worth checking out for its predicability.

Expansion of Clinicaltrials.gov

noreply@blogger.com (The Clinical Trials Wiki team) — Wed, 25 Feb 2009 17:07:00 +0000

Another interesting article in the last issue of NEJM on the expansion of clinicaltrials.gov, a topic which is very relevant to the development of ClinicalTrialsWiki.org.

Feb 19, 2009 Volume 360:824-830, NEJM
http://content.nejm.org/cgi/content/full/360/8/824

Effective since September 27, 2008 section 801 of the registration and reporting requirements of the FDA amendments Act has been expanded to include the mandatory reporting of basic results of clinical trials that were ongoing on or after September 27, 2007. As Dr. Allastair Wood suggests, the expansion of the FDA amendment section 801 is an essential step forward for the public availability of clinical trial information. The author also emphasizes that this advance remains to be completed by further broadening the reporting requirements and by providing a source of clear and comprehensible review of clinical trial results.

"Ethical clinical research should contribute to generalizableknowledge and improve human health. The dedication of patientswho take the risks to participate in clinical research is dishonoredwhen their data remain secret. Section 801 of the FDA AmendmentsAct will greatly expand the type and amount of information availableon clinical trials. The use of these data and the enhanced publicaccess to the FDA's database on clinical trials proposed inthis article will greatly improve the ability of investigatorsand others to assess the full set of results for a given intervention,whether FDA-approved or not, eventually leading to more accuratesystematic reviews, better clinical decision making, improvedpatient care, and improved research efficiency and safety."

Reading this article, I thought ClinicalTrialWiki.org is emerging just in time to complement the expansion of section 801 by:
1) Providing access to clinical trial information: The "news" tab of ClinicalTrialWiki.org will provide a comprehensive source of publicly available information on ongoing and completed Clinical Trials, easily accessible to health care professionals.
2) Opening the discussion to all caregivers via the "public views" tab.
3) Providing clear and understable analysis of clinical trials: In an effort to disseminate rigorous and unbiased information to the public, a panel of experts analyzes discusses and criticizes each clinical trial in the "expert views" tab.

Sneak preview

noreply@blogger.com (The Clinical Trials Wiki team) — Wed, 25 Feb 2009 06:47:00 +0000

Here's a glimpse into the backroom development that's going on while we're migrating servers. The main page has gotten another makeover (this isn't live yet):

I wanted to maintain a simple, clean interface while enhancing the functionality with a search bar that links directly into the wiki. Notice the fancy new "W" logo, which took all of 15 seconds to whip up on Photoshop. ;)

As always, let me know what you think.

CABG vs. stenting

noreply@blogger.com (The Clinical Trials Wiki team) — Wed, 25 Feb 2009 06:03:00 +0000

There's an excellent roundtable discussion on outcomes of coronary artery bypass graft (CABG) surgery vs percutaneous coronary intervention (PCI) in this week's New England Journal of Medicine. On the panel are Elizabeth Nabel, David Hillis, and Tom Lee. I had a chance to spend some time with the Nabel family last year -- she's a terrific cardiologist and currently Director of the National Heart, Lung, and Blood Institute.

Link to video after the jump.

In the international SYNTAX trial (ClinicalTrials.gov number, NCT00114972), funded by Boston Scientific (manufacturers of the TAXUS drug-eluting stent), 1800 patients with three-vessel or left main disease were randomly assigned to either revascularization with CABG or PCI involving drug-eluting stents. The paper published in NEJM (Serruys P et al. N Engl J Med 2009 ) shows us these dramatic Kaplan-Meir curves by treatment group:

The need for repeat revascularization was significantly lower with CABG, but the risk of stroke was significantly higher in the surgery group.

As Dr. Mohammadzadeh of CA has pointed out,

Many of the commentators have cited the difference in stroke rates in the two study groups as a justification for choosing pci over cabg. I do not see how their argument holds when there was such a vast difference between the post-procedural medical therapy that the two groups received. It seems to make good intuitive sense that if the surgical group had received as aggressive medical therapy, that not only the stroke rates may have been comparable, but the other end points such as mace would have crystallize more strikingly in favor of the surgical group. There is no question that there are patients that are better served by pci even in the setting of LM stenosis or 3-V CAD, but the bottom line should be that the patients should be given a fair and balanced explanation of their options before making a decision that is best suited for them.

Exactly. The risk vs. benefit analysis has long favored CABG in three vessel or LM disease, and this study should not really change clinical practice in these circumstances. However, it is striking that CABG patients often receive subpar antiplatelet therapy on the surgical floor. Establishing clinical directives for aggressive medical therapy in CABG patients might produce a welcome drop in stroke risk and rates of repeat revascularization.

And let's not forget that, despite the heated rhetoric surrounding this trial, we're really not considering one treatment strategy versus another. PCI has a secure and well-established place in the treatment of stable angina due to CAD.

The truth about comparative effectiveness

noreply@blogger.com (The Clinical Trials Wiki team) — Tue, 24 Feb 2009 17:08:00 +0000

It's all the rage now: Peter Orzag of OMB at the White House seems to think comparative effectiveness research is worth appropriations valued at $1.1 billion. Will it be worth the money?

I wasn't sure what "comparative effectiveness" actually meant, so I looked up the term at Consumer Reports:

What does it mean? Comparative effectiveness quite simply means comparing two or more treatments for a given condition. Studies may compare similar treatments, such as two drugs, or it may analyze very different approaches, such as surgery and drug therapy. Comparative effectiveness evaluations may focus only on the relative medical benefits and risks of each option, or they may also weigh both the costs and the benefits of those options. In some cases, a given treatment may prove to be more effective clinically or more cost-effective for a broad range of patients, but frequently a key issue is determining which specific types of patients would benefit most from it.

Transparent, unbiased, comparative research conducted without industry support? I'm all for it, so long as Congress doesn't bypass the clinical judgment of individual physicians -- or attempt to meter out care. Reminds me a bit of the Clinton-era attempt to develop standardized clinical recommendations for wide range of conditions, from chronic back pain to diabetes.

Here's a few independent takes at the NYT health blog, THCB, and The Gray Sheet (subscription required).

Crowdsourcing

noreply@blogger.com (The Clinical Trials Wiki team) — Tue, 24 Feb 2009 05:30:00 +0000

Interesting post today by Matthew Holt over at THCB. He interviewed Alexandra Carmichael, CEO of CureTogether.com, who claims to be at the cutting edge of something called Open Source Health Research.

Her company is trying to leverage the collective knowledge of disease communities to discover new connections between symptom patterns and underlying diagnoses. For example, after the jump you can see a graph generated by CureTogether.com's user surveys that illustrates the most frequent co-morbidities reported with vulvodynia.

Could information like this one day be useful in clinical decision-making? Perhaps, though it would be terribly difficult to interpret. How's a doctor supposed to tease apart co-morbidities that are spuriously linked from those that represent real clues as to common etiology? Is it ethical to make clinical decisions on the basis of uncorroborated Internet surveys?

It's my hope that generic user surveys like this get tied to more robust analysis, including an attempt to tease out confounders (it sounds like CureTogether.com is trying to do this). Currently the population sizes in question are probably far too small to drive any significant outcomes analysis, but expect to see more sites like this spring up in the coming years...

The real value may be in the sense of 'working towards a cure' that it gives to patients. Here's a money passage:

Me: Which kinds of takes us back to your prior life in genomics and ideas about GeneTwist. Care to speculate about the actual ways that CureTogether's data and community will actually lead to cures, together?
Alexandra: Yes, the grander vision for down the road is to integrate all kinds of data - genome scans, biomarker tests, streaming data from wifi health tracking gadgets. Collaboration with the larger research community as well, integrating our data with traditional clinical trial data. We already have researchers knocking on our doors wanting to start analyzing the data.
Me: So now "all" you have to do is get more people and more data into the site. How are you going to do that?
Alexandra: That's a good question! By talking to people like you, for a start. Health and condition-specific bloggers seem happy to help spread the word. Disease foundations have also approached us, eager to help out. And media have all been coming to us so far. I just started the process of seriously getting out there in the past couple of weeks - I'm even on Twitter @accarmichael. It's still mostly a grass-roots effort though. If and when we get funding, that could change. But it's very rewarding work. At the end of the day, I know I've spent my time helping people and working to make a difference.

Reading her comments, it strikes me that we face a similar challenge at ClinicalTrialsWiki.org in trying to develop a core community of users who are motivated to populate our site with discussion and commentary.

We're moving!

noreply@blogger.com (The Clinical Trials Wiki team) — Mon, 23 Feb 2009 15:26:00 +0000

We're moving the webserver for ClinicalTrialsWiki.org from my personal computer to a more permanent residence. To do that, we're taking the site down for a couple of days as we set up shop in our new location (which has 4-5x more storage space), and re-build our wiki there.

Thanks for your patience!