Have you ever wondered about what goes on behind the scenes—how new drugs are magically produced and brought forth? We’ll continue to take the mystery out of clinical research and drug development and to provide background information so that both patients and physicians can make more informed decisions about whether they wish to participate in clinical trials or not.
To develop a medicine, from the time of discovery of the chemical until it reaches your drug store, takes an average of 12-15 years and the participation of thousands of volunteers in the process of clinical trials (Fig 1).
Very few people participate in clinical trials—it is even less than 5% for patients with cancer—due to lack of awareness or knowledge about the process. We’ll go into detail about how drugs are developed in later posts.
An inadequate number of volunteers is one of the major bottlenecks in drug development, delaying the product’s release and usefulness to the public. Of course, many people may suffer or even die during this wait, if they have an illness that is not yet otherwise treatable. So if you want new medicines, learn about—and decide if you wish to participate in—the process. I have, as a volunteer subject, researcher, and advocate.Continue reading…
Thursday I traversed the frozen surface of the pond for perhaps the last time this season. The ice is thinning quickly. I had on my rubber boots and stayed what I felt to be a safe distance from shore: should I break through, the water would not be over my head. I got some fantastic photos and considered the little adventure a success. However, over dinner that evening when I mentioned that I’d been on the pond earlier, David and Peter were furious. Peter wouldn’t calm down until I promised I wouldn’t go out again.
I have always considered fear the enemy; something to conquer and overcome and I’ve had a lot of practice. Being risk adverse and scrappy has been an asset now that I have lung cancer. As a participant in a phase I clinical trial, there is the potential for unforeseen and possibly life threatening side effects of treatment itself. Before you are given your first dose of an experimental drug, you must read through and sign consent forms which acknowledge this risk. It is something most healthy persons would never do. When you have a terminal illness, it is similar to coming to the edge of a ravine with a tiger on your trail. Between you and safety is a rickety bridge that may or may not support your weight. However, even chancy passage is an easy decision when the alternative is certain death.
In the fall of 2009, at the height of fears over swine flu, our research group discovered that a majority of clinical trial data for the anti-influenza drug Tamiflu ― data that proved, according to its manufacturer, that the drug reduced the risk of hospitalization, serious complications and transmission ― were missing, unpublished and inaccessible to the research community. From what we could tell from the limited clinical data that had been published in medical journals, the country’s most widely used and heavily stockpiled influenza drug appeared no more effective than aspirin.
After we published this finding in the British Medical Journal at the end of that year, Tamiflu’s manufacturer, Roche, announced that it would release internal reports to back up its claims that the drug was effective in reducing the complications of influenza. Roche promised access to data from 10 clinical trials, 8 of which had not been published a decade after completion, representing more than 4,000 patients from every continent except Antarctica. Independent verification of the data seemed imminent. But more than two years later, and despite repeated requests, we have yet to receive even a single full trial report. Instead, the manufacturer released portions of the reports, most likely a very small percentage of the total pages. (One of us, Tom Jefferson, has been retained as an expert witness in a lawsuit relating to some of these issues.)
Eric Topol was once a lowly (well not that lowly) cardiology professor at the University of Michigan, but he’s now without question the leading renaissance man in health care technology. Virtually every week sees him on some big stage disgnosing his own heart murmur with an iPhone app or showing off how his sleep brain waves and his genome interact or don’t.
His new book, The Creative Destruction of Medicine is a tour de force romp through basically every type of cool new medical technology. He covers the Cloud/Web/Wireless/Sensor phenomenon from both a social, transactional and diagnostic point of view–leaning heavily on his connection to the West Wireless Health Institute which he helped persuade Gary & Mary West to fund. He’s the creator of a new medical school program at Scripps focusing on the genomics and proteomics revolution, and the book covers in great detail the evolution of the human genome project and its impact on disease discovery (coming eventually) and matching patients to the right drug (available more or less now). Finally he was of course the head of Cardiology at the Cleveland Clinic where he not only was heavily involved in the testing of tPA (the drug that built Genetech) but also in unveiling the problems with Vioxx not limited to the drug itself but also concerning Merck’s behavior at the time. (Remember Dodgeball?)
A Museum of Modern Art exhibit by Michael Burton once proposed that human beings themselves would be the soil for a “future farm:”
Future Farm predicts that the emerging pharmaceutical research in harvesting adult stem cells from fat tissues and its convergence with future nanotechnologies, will bring with it scenarios that reconsider the body as income. We live in a world where industries exist to offer financial rewards for those willing to sell a kidney or produce hair to beautify others. Industries have grown to facilitate transplant tourism as a result of the success of contemporary surgery. And scientific and technological advances continue to bring new possibilities for the practice of farming the body.
This may seem like an overly dramatic or even science-fictionalized description of desperation due to poverty and larger economic trends. But the global economic race to the bottom has now so influenced medical research that Burton’s dark vision is coming closer to realization.
A recent article by Bartlett & Steele and a book by Carl Elliott describe the rise of “contract research organizations” that organize the initial phases of drug trials. Bartlett and Steele choose a provocative metaphor to describe the trend:
To have an effective regulatory system you need a clear chain of command—you need to know who is responsible to whom, all the way up and down the line. There is no effective chain of command in modern American drug testing. Around the time that drugmakers began shifting clinical trials abroad, in the 1990s, they also began to contract out all phases of development and testing, putting them in the hands of for-profit companies.
Saturday’s New York Times portends more trouble for big Pharma. The headline is wrapped up in an examination of foreign corrupt practices, but the bigger issue is that clinical trials have hidden serious adverse events. The recent allegations that GSK hid data about heart attacks from an Avandia trial conducted abroad highlight the reality that over the last 20 years or so it’s been very hard to recruit patients for clinical trials in the US. It’s expensive to find patients, and the numbers of patients available near centers has not proved enough. The answer has been to go to places with lots of people and lower costs, like India.
One obvious consequence is that few of the significant advantages of Internet connectivity and patient community which have been developing in recent years have been adopted as part of these pre- or post market trials. Several online communities–notably PatientsLikeMe–have been running their own studies but they have typically been observational studies and haven’t had much acceptance from Pharma or regulators.
We entered the 21st century awash in “evidence” and determined to anchor the practice of medicine on the evidentiary basis for benefit. There is the sense of triumph; in one generation we had displaced the dominance of theory, conviction and hubris at the bedside. The task now is to make certain that evidence serves no agenda other than the best interests of the patient.
Evidence-based medicine is the conscientious and judicious use of current best evidence from clinical care research in the management of individual patients”. [1,2]
But, what does “judicious” mean? What does “current best” mean? If the evidence is tenuous, should it hold sway because it is currently the best we have? Or should we consider the result “negative” pending a more robust demonstration of benefit? Ambiguity is intolerable when defining evidence because of the propensity of people to decide to do something rather than nothing.  Can we and our patients make “informed” medical decisions on thin evidentiary ice? How thin? Does tenuous evidence mean that no one is benefited or that the occasional individual may be benefited or that many may be benefited but only a very little bit?Continue reading…
Amid hundreds of amendments offered in the health care reform debate, there is a non-partisan, non-controversial gem that will both help patients and speed the search for new cures to deadly diseases.
Senators Sherrod Brown [D-OH] and Kay Bailey Hutchison [R-TX] have proposed an amendment that would encourage patients with life-threatening diseases or conditions to participate in clinical trials by requiring private insurers to cover patients’ routine care. It is essential that the Senate pass this amendment as part of health care reform.
As a cancer physician, I can speak to the benefits of clinical trials in my field of oncology. Virtually every advance in cancer prevention, screening, and treatment over the last 40 years can be traced directly to clinical trials – colonoscopies; curative treatment for testicular cancer; improved survival for most pediatric cancers; chemotherapy after surgery to prevent recurrence; new personalized therapies that target specific characteristics of cancer cells; and symptom management. Thanks primarily to the knowledge gained through clinical trials, today two-thirds of cancer patients survive at least five years after diagnosis, compared with only half in the 1970s.Continue reading…