Sometimes, a book title takes on a larger meaning than the book itself. The Ugly America, [1958] was made into a feature film with Marlon Brando [1963] and it lives on as a moniker to the crude American capitalist overseas who exploits the locals, even though that’s not exactly the theme of the book. I thought of it when I first looked into the Clinical Research Organizations, reading the ACRO "white paper" about how globalized clinical trials were good for developing countries. It smelled like rotten fish to me for two reasons: it reeked of exploitation and I wondered about the usefulness of clinical trials in countries where the problems aren’t in the DSM but rather in their disparate sociology [see slumdog trials: on a war footing…]. …As India attempts to craft new rules for governing clinical trials, another report focuses attention on an underlying problem plaguing both regulators and the pharmaceutical industry – the number of patient deaths attributed to trials and the contentious issue of compensation by drugmakers. To wit, as many 2,868 deaths occurred during trials between 2005 to 2012, although only 89 have been attributed directly to the studies. However, compensation was paid in just 45 cases. Last year, 16 of 436 deaths among participants were attributed to trials, although compensation was paid in only two cases.
These sorts of patterns last month prompted the Indian Supreme Court to harshly criticize regulators for shoddy oversight and enforcement. An amended rule would require the Drugs Controller of India to ensure trials are conducted with good clinical practices, approved by ethics committees, registered before patients are enrolled, provide annual status reports and report adverse events with 10 days of occurrence [back story]. Compensation, however, is causing tension. India’s Central Drugs Standard Control Organization wants to require drugmakers and contract research organizations to make payments determined by the Drug Controller General of India within 30 days of injury or death. If payment is not made, CDSCO can cancel a trial and ban the drugmaker or CRO from conducting studies in India.
As we reported last month, the Association of Clinical Research Organizations reacted by saying India would become “an extremely difficult and risky place to do business… ACRO is in the process of assessing the political, legal, regulatory and business climate in India with the hope that we can form a strategy to move forward.” We also wrote that clinical trials conducted by global drugmakers and their proxies have generated increased scrutiny in recent years as the pharmaceutical industry seeks to run studies in countries with lower costs and populations where patients are not exposed to as many medications that can confound results. India has been a prime example.
However, the country may be losing its edge. The domestic market was worth about $485 million in 2011, according to the Frost & Sullivan market research firm, which predicts this could double to $1 billion by 2016. And the relatively low cost of conducting trials and a fast-growing population of 1.2 billion should mean that India remains a desirable destination. But less than 1.5 percent of global trials take place in India, according to the Indian Society for Clinical Research. Nonetheless, the large pool of willing trial participants almost guarantees that drugmakers and CROs will not lack for subjects. The government, however, is trying to make clear that greater accountability is required. For instance, the number of patients deaths linked to clinical trials between 2005 and 2007 was small – a total of just 11 – but compensation was never paid in any of these cases.
Then recently, I ran across this [see #4]:
5 interesting things from Quintiles IPO filing
MedCity News
by Stephanie Baum
February 15, 2013 9:16 pmThe rumors, it seems were true after all. In an environment where initial public offerings by life science companies have all but dried up, Quintiles, the largest contract research organization, has filed documents with the Securities and Exchange Commission seeking to raise up to $600 million in an IPO. This is Quintiles’ second IPO. Its first was in 1994 but it went private again in 2008 with private equity owners TPG Capital and Bain Capital. The move comes less than a year after Dennis Gillings, the founder, stepped down as CEO and became executive chairman. When the rumors of an IPO were just beginning to rev up, Jessica Gladstone, a senior analyst at Moody’s told Bloomberg: “I view the fact that they have a new CEO now as potentially a sign that they’re preparing their next leg of growth or next strategy, which could include an IPO…An IPO could also be a way to reduce leverage and an exit strategy for the owners.” S1 filings often yield some interesting facts about the company and its place in in the market it would usually shield from view. Here are 5 interesting things gleaned from its S1 filing:
…"de-identified electronic health record data representing more than 40 million patients" will get one’s attention. And how do they get that kind of access?
It seems to me that everything that has anything to do with the clinical trials industry has big numbers attached. millions of records. billions of dollars. thousands of deaths. And there’s often some questionable piece in the story.
There is an old saying about evidence based medicine: evidence based medicine needs medicine based evidence. Back in the day, clinical trials were carried out in real clinics by real physicians who studied real patients. With the rise of commercial and academic CROs, patients came to be viewed as commodities. When was the last time you heard of a CRO providing follow-up care to the patients enrolled in trials? With the rise of commercial and academic CROs, corners were cut to maximize profit. Cutting corners took several forms. One was to make the inclusion criteria for a trial elastic – turning a blind eye to disqualifying comorbidities. Another was to fudge the inclusion criteria – rating up the Hamilton depression score to meet enrolment targets. That has been well documented. These are the ways we got to see response rates of 85% reported for placebo in psychotic depression in trials sponsored by Corcept Therapeutics in eastern Europe. A third form of cutting corners involved glossing over toxicity events. There is no shortage of examples for that, like Glaxo Study 329 of paroxetine in youth.
The great sociologist Jane Jacobs put it this way years ago: “There are many fine points to medical ethics, and some difficult puzzles, but the most rudimentary morality is the line between the guardian and commercial (traditions). It’s as crucial that physicians understand it as it is that lawyers recognize that when they go into guardian service they can’t morally also be in service to clients seeking to influence legislation or regulatory decisions.” [Systems of Survival, Random House 1992].
In the CRO world we have pretend physicians recruiting pretend patients into clinical trials that pretend to test efficacy while being biased for an outcome that suits the commercial sponsor. So, when corporations view patients as commodities, why are we surprised that they resist compensation for injury?