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Tomorrow WHO will call for a new policy in clinical trial transparency that is transparently absurd, absurdly transparent, and deleterious to the public health.
In its effort to develop worldwide standards of trial registration, WHO formally launched its International Clinical Trials Registry Platform (ICTRP) in April 2005. Tomorrow WHO plans to go public with its proposed final policy on which trials should be registered, and when. The policy will recommend registration of every “interventional study” (i.e. every trial for every intervention, whether marketed or not; whether randomized or not; and whether early phase or late phase).
Give me a break.
WHO wrongly claims that its policy is justified by the need to meet “ethical obligations to study participants.” Those obligations are already met in full, by disclosures to regulators, to independent review boards and ethics committees overseeing each trial, to every clinical investigator participating in each trial, and most importantly to every patient.
Ironically, while not remedying an ethical issue, WHO’s proposal may create one. In its call for registration of exploratory studies, particularly Phase I studies, WHO would fill the registry with vast amounts of data of no medical value. Every user would be compelled to sift this mountain of chaff to find the kernels of useful information; and might mistake the chaff for wheat. Phase I and other exploratory studies serve a narrow purpose and outside that context their results are inherently unreliable. Registering these trials or disclosing their results would at best confuse patients and encourage false hopes. At worst, where non-experimental drugs are being tested for new indications, physicians might inappropriately rely on disclosed trial information to make prescription decisions before confirmatory safety or efficacy trials have even been started.
From an ethical standpoint it is not at all clear what public health purpose is being served by this disclosure, nor which individuals it will benefit.
And then there are the myriad questions surrounding IP issues.
WHO’s policy of registering all interventional studies will make it harder or impossible for research based companies to secure important IP around selection inventions, manufacturing and formulation claims, and important new uses. Without this protection, sponsors may either abandon such research or else increase their precautionary patent filings at a time of high project attrition. This will drive up the cost of development, reduce the number of projects, and delay the progress of products to the marketplace.
The IOM has a better idea. In a recent workshop report they endorsed a more practical and beneficial guiding principle “Avoid reducing the incentive to do clinical research, whether public or privately funded.”
The net effect of the proposed WHO policy is that patients will wait longer for fewer and more expensive medicines, in exchange for a trial registry policy that benefits nobody.
That’s a Geneva Convention we can do without.
A recent stufy by the Tufts Center for the Study of Drug Development (home of Red Sox fan Joe DiMasi who is also the lead author of the study) found that “genomic technologies have helped to significantly increase the number of drug candidates that enter clinical trials.” According to the Center, “During 2003-05, the rate at which the 10 top selling U.S. drug companies initiated clinical trials for new drug candidates rose by 52 percent, following a 21 percent decline from 1993-97 to 1998-02.”
In an interview with GenomeWeb News sister publication BioCommerce Week, Tufts Center director Ken Kaitin noted though the study did not seek to learn why R&D productivity increased or to address technological tools that might have helped enable it.” Kenneth Kaitin said discussions he has with officials from big pharma indicate that genomic technologies and methodologies have played “an increasingly important role” in driving the improvement. These tools and methods include mass spectrometry, genome sequencing, gene-expression, high-content screening, and SNP-genotyping.
“I don’t think there is any question [genomic tools are] playing an increasingly important role in candidate selection for products that enter clinical testing,” Kaitin told . “Every company that I speak to now is saying that a significant improvement in their ability to select compounds for clinical development is access to these tools.”
Now the question is: can we apply the same science being used to improve drug discovery — characterized by the emergence of more validated drugs hitting more precise targets — to the process of drug development. The opportunity is enormous. Which is why supporting the Critical Path Initaitve is so critical.
The MSM is so predictable. Rather than reporting on the success of Part D enrollment the stories are now all about “the penalty.” As Bob Goldberg has mentioned (see below) this draconian measure averages out to between about $2-$5 a month. But this fact, not surprisingly, hasn’t been reported. The issue that the media, lawmakers, and pundits have missed is that when you don’t have a deadline people who are eligible and entitled to Federal programs don’t sign up. A spot-on example is CHIP. As mayors and governors nationwide have bemoaned — if all of the CHIP-eligible families in the US were actually using the program, the numbers of children without health care coverage would plummet. But, there’s no deadline so there’s no urgency.
And that’s the ultimate penalty.
West Virginia Governor Joe Manchin has decided not to formally respond to a recent column in the Charleston Gazette by Dr. Alan Sager of Boston University critical of the state’s efforts to implement a 2004 state law intended to curb soaring prescription drug costs.
In the April 27 column, Sager complained that the provisions of the act are being implemented “much too slowly.”
Comment from the Governor’s office …
“We think they’re moving in the right direction,” said Lara Ramsburg, the Governor’s communications director. “We’re not going to spend of lot of time worrying about responses.”
Well I did respond and here’s my letter (which appeared in the May 14 edition of the Gazette) …
Drug comparison useless and wrong
May 14, 2006
In his commentary in the April 27 Charleston Gazette, Dr. Alan Sager makes the obscene argument that since the street price of heroin and cocaine has decreased four-fifths between 1981 and 2000, so too should the costs of prescription pharmaceuticals.
His comparison couldn’t be more useless — or more wrong. He points out that in 1981 the “average retail price per pharmaceutical” was $9.50 and that in 2000 the average rose to $40.11. But this is a useless statistic because, one, it begs the question, what’s an average pharmaceutical?; and, two, it supposes that we’re dealing with the same basket of similar products.
In 1981 there were far fewer effective medications for almost every disease (most notably hypertension, high cholesterol and diabetes) and biologic therapies for cancer, multiple sclerosis, etc., were more science fiction than science. We’ve come a long way from bench to bedside in those years, and millions of Americans are leading healthier, more productive lives because of these advances.
In 1981, my parents gave me an electric typewriter for my birthday. It cost $125. Using Sager’s logic, I could make the argument that in 1981 a “word processor” cost $125 and in 2000 it cost $2,500. But would anyone accept that a typewriter and a laptop computer are comparable? I think not.
Peter J. Pitts
Scott Hensley is one of the country’s best health care reporters and his article on the risks and benefits of drugs for RA proves it. Scott’s piece is fairly balanced, however as I noted in an email to him: Not bad as far as most pieces of this genre…but if you had delineated between cancers and put this study into the context of other similar projects if would have made people rest easy rather than give the Grassleys and Sid Wolfes of the world more red meat for slowing down drug development.
For instance, ” Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma, and standardised incidence ratio (SIR) is greatest for those treated with anti-tumour necrosis factor (anti-TNF) therapies; however, differences between therapies are slight, and data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma, a new report indicates.
It has previously been reported that methotrexate (MTX) and anti-TNF therapies might be independently associated with an increased risk of lymphoma. However, small sample sizes and selected study populations in these studies could not confirm this association.
To investigate this issue further, Frederick Wolfe, MD, and Kaleb Michaud, MS, with the National Data Bank for Rheumatic Diseases, Arthritis Research Foundation, in Wichita, Kansas, United States, prospectively studied 18 572 enrolees in the National Data Bank for Rheumatic Diseases (NDB).
Patients were surveyed twice a year. Reported cases of potential lymphoma were further investigated. The expected number of cases of lymphoma was determined by using data from the Survey, Epidemiology, and End Results (SEER) cancer data resource.
Overall, 88 lymphomas were identified, 59 of which occurred prior to NDB enrolment and 29 of which occurred after NDB enrolment and during the period of intensive follow up.
The overall SIR for lymphoma, regardless of treatment, was 1.9. For patients receiving biologics, SIR was 2.9 (95% CI 1.7-4.9). For those taking infliximab, with or without etanercept, the SIR was 2.6 (95% CI 1.4-4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95% CI 1.9-7.5). The SIR for MTX was 1.7 (95% CI 0.9-3.2), and for those not receiving MTX or biologics, the SIR was 1.0 (95% CI 0.4-2.5).
Lymphoma was associated with increasing age, male sex, level of education, and comorbidities. The Cox regression hazard ratios and 95% CIs for these variables were 1.58 per 10-year increase in age (95% CI 1.16-2.18); 3.70 (95% CI 1.79-7.68) for male sex; 1.16 (95% CI 0.99-1.37) for education; abd 1.30 (95% CI 1.10-1.54) and for comorbidity.
“The results of this study show that lymphoma is increased in RA compared with the general population,” Dr. Wolfe and colleagues conclude. However, even a sample of more than 18 500 patients could not demonstrate significant differences among the studied groups, because of the rarity of lymphoma, they note.
“It seems possible that the apparently increased rates of lymphoma are, in fact, reduced by therapy, and that the ‘increase’ may reflect channelling bias whereby patients with the highest risk of lymphoma preferentially receive anti-TNF therapy,” the researchers conclude.
“It appears that neither clinical trial data nor data from the current study are sufficient to establish a causal relationship between RA treatments and the development of lymphoma,” they add.
Arthritis Rheum 2004;50:1740-1751. “Lymphoma in rheumatoid arthritis: The effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients”
There is also this study http://www.arthritis-research.org/Documents/breast_ca_ACR2005.ppt
and this one http://www.arthritis-research.org/Documents/lung%20cancer_ACR2005.ppt
PS. The fact that drug companies support research does not make the research wrong. If that were the case, then no drug would work since all research submitted to the FDA is done by drug companies…
From a Washington Post Story: ” Grassley said the bill would make up for an estimated $1.7 billion in lost penalty revenue over five years by reducing a “stabilization fund” aimed at helping private managed-care health plans take care of older Americans. “
So let’s see….penalize seniors who sign up early by taking away their discount and take money away from an effort to keep seniors healthy in order to save laggards $2-5 a month? This is election year grandstanding of the worst sort….
ON THE HEALTH CARE FRONT: Yesterday, according to Mark McClellan, administrator for the Centers for Medicare and Medicaid Services and the hardest working man in health care, about 40,000 to 50,000 people were on the agency’s Web site site at any given moment.
“We’ve seen a real surge,” McClellan said. “The deadline is making a difference.”
WHILE ON THE POLITICAL FRONT: According to an AP story, Representative. Nancy Johnson (R, CT) took a swipe at Democrats, saying she believes the program has been quite successful, and enrollment might have been closer to 100 percent “if the Democrats had put the welfare of our seniors ahead of their own political ambition.”
You go girl.
The OIG stance is typically government: make a straightforward program that works well in the private sector a cumbersome and daunting process that discourages consumer participation and then makes any corporate deviation from the regulations or their interpetation by Asst. US attorneys or self-styled consumer groups grounds for criminal investigation or litigation.
Which goes to show you what life would be like if the government took direct control of the Medicare drug benefit….bad enough the nit-wits in OIG have screwed this one act of charity up…what would happen if every part of the pharmaceutical business was under government control?
Excellent article in today’s Financial Times about the impact the rapidly declining cost and increasing precision of clinical informatics is having on prescribing decisions and the Pharma model of simply marketing a drug based on FDA data. The article describes how health plans are developing better post market and predictive decision-making models on who gets what within the framework of disease managment. And it will soon be possible to integrate clinical data with some genomic data as well. Where is Pharma on all this? According to the FT article: “in a world where whoever controls the gold often rules, drugs companies no longer have a firm grasp on the most precious commodity: information.” See the article below..
I have been saying for years that Pharma has to get into the trenches and start looking at how their products actually work and where they work best to stay in the game and stay ahead of the price control crowd. What they spend on traditional marketing should be spent on developing sophisticated data mining and data analysis systems…it would deliver better value to both company and customers alike.
It’s PDUFA reauthorization time and the usual suspects are trotting out the usual evasive gabble.
PDUFA MYTH #1: Since drug companies provide about 40% of FDA funding via PDUFA, the agency is “beholden” to Big Pharma.
TRUTH: How can FDA be “in the pocket of the pharmaceutical industry” when the industry has nowhere else to go? Where’s the leverage? It’s FDA or nothing pal. The leverage is on the other side.
Proper retort to ignorant comment — “Industry pays FDA to approve drugs.”
Wrong! FDA gets paid to review drugs. (And they certainly don’t all get approved now, do they?)
More myth-busting to follow.
Send me your favorite PDUFA myths and I’ll post them. I can be reached at firstname.lastname@example.org.