Reference no: EM131036566 , Length: 2
Summarize the assignment as a one page paper (do not exceed two pages). (be sure to include each point and briefly in paper format).
Assignment
- Behind the scenes, however, MK-869 was starting to unravel. True, many test subjects treated with the medication felt their hopelessness and anxiety lift. But so did nearly the same number who took a placebo, a look-alike pill made of milk sugar or another inert substance given to groups of volunteers in clinical trials to gauge how much more effective the real drug is by comparison. The fact that taking a faux drug can powerfully improve some people's health-the so-called placebo effect-has long been considered an embarrassment to the serious practice of pharmacology.
o MK-869 wasn't the only highly anticipated medical breakthrough to be undone in recent years by the placebo effect. From 2001 to 2006, the percentage of new products cut from development after Phase II clinical trials, when drugs are first tested against placebo, rose by 20 percent. The failure rate in more extensive Phase III trials increased by 11 percent, mainly due to surprisingly poor showings against placebo. Despite historic levels of industry investment in R&D, the US Food and Drug Administration approved only 19 first-of-their-kind remedies in 2007-the fewest since 1983-and just 24 in 2008. Half of all drugs that fail in late-stage trials drop out of the pipeline due to their inability to beat sugar pills.
-Why are inert pills suddenly overwhelming promising new drugs and established medicines alike? The reasons are only just beginning to be understood. A network of independent researchers is doggedly uncovering the inner workings-and potential therapeutic applications-of the placebo effect. At the same time, drugmakers are realizing they need to fully understand the mechanisms behind it so they can design trials that differentiate more clearly between the beneficial effects of their products and the body's innate ability to heal itself.
o The roots of the placebo problem can be traced to a lie told by an Army nurse during World War II as Allied forces stormed the beaches of southern Italy. The nurse was assisting an anesthetist named Henry Beecher, who was tending to US troops under heavy German bombardment. When the morphine supply ran low, the nurse assured a wounded soldier that he was getting a shot of potent painkiller, though her syringe contained only salt water. Amazingly, the bogus injection relieved the soldier's agony and prevented the onset of shock.
o In a 1955 paper titled "The Powerful Placebo," published in The Journal of the American Medical Association, Beecher described how the placebo effect had undermined the results of more than a dozen trials by causing improvement that was mistakenly attributed to the drugs being tested.
o Volunteers would be assigned randomly to receive either medicine or a sugar pill, and neither doctor nor patient would know the difference until the trial was over. Beecher's double-blind, placebo-controlled, randomized clinical trial-or RCT-was enshrined as the gold standard of the emerging pharmaceutical industry. Today, to win FDA approval, a new medication must beat placebo in at least two authenticated trials.
-Potter's ambitious plan for a collaborative approach to the problem eventually ran into its own futility boundary: No one would pay for it. And drug companies don't share data, they hoard it. But the NIH conference launched a new wave of placebo research in academic labs in the US and Italy that would make significant progress toward solving the mystery of what was happening in clinical trials.
o Benedetti, 53, first became interested in placebos in the mid-'90s, while researching pain. He was surprised that some of the test subjects in his placebo groups seemed to suffer less than those on active drugs. But scientific interest in this phenomenon, and the money to research it, were hard to come by. "The placebo effect was considered little more than a nuisance," he recalls. "Drug companies, physicians, and clinicians were not interested in understanding its mechanisms. They were concerned only with figuring out whether their drugs worked better."
o Now, after 15 years of experimentation, he has succeeded in mapping many of the biochemical reactions responsible for the placebo effect, uncovering a broad repertoire of self-healing responses. Placebo-activated opioids, for example, not only relieve pain; they also modulate heart rate and respiration.
o Benedetti often uses the phrase "placebo response" instead of placebo effect. By definition, inert pills have no effect, but under the right conditions they can act as a catalyst for what he calls the body's "endogenous health care system." Like any other internal network, the placebo response has limits. It can ease the discomfort of chemotherapy, but it won't stop the growth of tumors. It also works in reverse to produce the placebo's evil twin, the nocebo effect. For example, men taking a commonly prescribed prostate drug who were informed that the medication may cause sexual dysfunction were twice as likely to become impotent.
o In other words, one way that placebo aids recovery is by hacking the mind's ability to predict the future. We are constantly parsing the reactions of those around us-such as the tone a doctor uses to deliver a diagnosis-to generate more-accurate estimations of our fate. One of the most powerful placebogenic triggers is watching someone else experience the benefits of an alleged drug. Researchers call these social aspects of medicine the therapeutic ritual.
-In a study last year, Harvard Medical School researcher Ted Kaptchuk devised a clever strategy for testing his volunteers' response to varying levels of therapeutic ritual. The study focused on irritable bowel syndrome, a painful disorder that costs more than $40 billion a year worldwide to treat. First the volunteers were placed randomly in one of three groups. One group was simply put on a waiting list; researchers know that some patients get better just because they sign up for a trial. Another group received placebo treatment from a clinician who declined to engage in small talk. Volunteers in the third group got the same sham treatment from a clinician who asked them questions about symptoms, outlined the causes of IBS, and displayed optimism about their condition.
o Not surprisingly, the health of those in the third group improved most. In fact, just by participating in the trial, volunteers in this high-interaction group got as much relief as did people taking the two leading prescription drugs for IBS. And the benefits of their bogus treatment persisted for weeks afterward, contrary to the belief-widespread in the pharmaceutical industry-that the placebo response is short-lived.
o Studies like this open the door to hybrid treatment strategies that exploit the placebo effect to make real drugs safer and more effective. Cancer patients undergoing rounds of chemotherapy often suffer from debilitating nocebo effects-such as anticipatory nausea-conditioned by their past experiences with the drugs. A team of German researchers has shown that these associations can be unlearned through the administration of placebo, making chemo easier to bear.
-Ten years and billions of R&D dollars after William Potter first sounded the alarm about the placebo effect, his message has finally gotten through. In the spring, Potter, who is now a VP at Merck, helped rev up a massive data-gathering effort called the Placebo Response Drug Trials Survey.
o Under the auspices of the FNIH1, Potter and his colleagues are acquiring decades of trial data-including blood and DNA samples-to determine which variables are responsible for the apparent rise in the placebo effect. Merck, Lilly, Pfizer, AstraZeneca
o To really do the best for your patients, you want the best placebo response plus the best drug response."
-The pharma crisis has also finally brought together the two parallel streams of placebo research-academic and industrial. Both are exploring innovative trial models that treat the placebo effect as more than just statistical noise competing with the active drug.
o Ironically, Big Pharma's attempt to dominate the central nervous system has ended up revealing how powerful the brain really is. The placebo response doesn't care if the catalyst for healing is a triumph of pharmacology, a compassionate therapist, or a syringe of salt water. All it requires is a reasonable expectation of getting better. That's potent medicine.