I’m Thinking Of Participating In An Arthritis Research Study And I’m Concerned About Placebo…

As long as medical research has existed, it has been known that a fake treatment, made from an inactive substance such as sugar, distilled water, or saline (salt water), can have a "placebo” effect.

What this means is that the sham medication can sometimes improve a patient's condition because the person has the expectation that it will work. For any given medical condition, it's not unusual for one-third of patients to feel better in response to treatment with placebo.

According to Robert DeLap, M.D., head of one of the Food and Drug Administration's Offices of Drug Evaluation,“…expectation is a powerful thing… the more you believe you're going to benefit from a treatment, the more likely it is that you will experience a benefit."

To sort out what the placebo effect is doing versus what the drug under consideration is accomplishing, companies seeking FDA approval of a new treatment often use placebo-controlled drug studies. If patients on the new drug do significantly better than those taking placebo, the study can confirm that the medicine is effective.

Researchers have been studying the placebo effect for decades. In 1955, researcher H.K. Beecher published his seminal paper "The Powerful Placebo," in which he concluded that, across the 26 studies he reviewed, an average of about one-third of patients responded to placebo.

In the 1960s, other studies showed the potential physiological effects of sham pills--they tended to speed up pulse rate, increase blood pressure, and improve reaction speeds when participants were told they had taken a stimulant, and had the opposite physiological effects when participants were told they had taken a sleep-producing drug.

Questions still remain about the complex interrelationship among psychological and physiological mechanisms that contribute to the placebo effect. Today's brain imagery techniques do lend support to the theory that thoughts and beliefs not only affect one's psychological state, but also cause the body to undergo actual physiological changes. Why this occurs may be explained by the results of a recent study.

In a study published in the July 19, 2007 issue of Neuron, researchers at the University of Michigan, studied the nucleus accubens (NAC), an area deep in the brain that is known to play a role in reward expectation.

Previous research has indicated that the NAC may be involved in the placebo effect.

The researchers told study participants that they were testing a new pain-killing drug and that the participants would receive either the drug or a placebo. But the researchers gave all of the participants a placebo injection of salt solution.

The participants rated their expectation of the pain-killing effects of the "drug," as well as the level of pain relief they felt with and without the "drug" from a painful injection of saline (salt water solution) in their jaw muscle.

For the first experiment, the researchers used positron emission spectroscopy- a new imaging procedure- to measure dopamine release from the NAC. Dopamine is a neurotransmitter -- a chemical trigger of the brain's reward response.

The greater the participants' expectation of the pain relief from the "drug," the greater the dopamine release from the NAC. In addition, participants who reported more relief from the "drug" when they did experience pain showed greater NAC activity when they received the placebo before the pain.

In another experiment, the researchers told the subjects to expect monetary rewards of different amounts, while scanning their brains with functional magnetic resonance imaging. The participants who showed more activation of the NAC during this reward processing also showed greater anticipation of the effectiveness of a placebo.

According to the study authors, the findings support the theory that the NAC system may need to be activated to allow the placebo effect to occur.

Researchers point towards other physiological responses such as the fight-or-flight response that help human beings to survive and cope as being similar to placebo response. For example, if a frightening experience occurs while a person is walking down a particular street, the next time they are walking down the same street, physiological responses they felt before may kick in.

Another 1997 Canadian study employed placebo tablets in a study of benign prostatic hypertrophy (enlargement of the prostate gland).

More than half the men who got placebo pills reported significant relief from their symptoms, including faster urine flow. Head researcher, J. Curtis Nickel, hypothesized that the patients' positive expectations may have caused smooth muscle relaxation by decreasing nerve activity affecting the bladder, prostate and urethra leading to a therapeutic effect. Study participants on placebo complained of side effects as well. This is termed a "nocebo" effect. Nocebo responses included impotence, reduced sex drive, nausea, diarrhea and constipation.

It's this powerful placebo effect, coupled with the fact that many medical conditions such as arthritis naturally wax and wane, that can make it difficult to know if an improvement is due to drug effect.

While the FDA doesn't require that a drug study include a placebo control group, it does require a study to be designed to show a drug's safety and effectiveness. An example would be "head-to-head" studies, which compare the experimental drug to an existing treatment.

Another example would be a comparison with historically controlled studies, which compare the new drug's effects with information obtained from the past about the response of a medical condition to specific therapies.

Still, a placebo controlled study provides the best insight into what a treatment can accomplish.

The use of placebo, though, can really complicate matters. Occasionally, in certain conditions, the magnitude of placebo response makes it very difficult to statistically differentiate the placebo effect from true drug effect. An example would be arthritis where symptoms tend to wax and wane.

Sometimes, researchers and FDA must look at each treatment individually to decide if the use of placebos is appropriate and ethical. Much medical research does not involve a placebo control because it is deemed to be unethical.

To determine whether a placebo-controlled trial is acceptable, pharmaceutical companies and the FDA ask certain questions such as: For what condition is this drug being tested? What is the natural progression of the disease? How serious is the risk if a patient gets a placebo rather than an active treatment?

As an example, in a cancer study, a placebo control may not be acceptable whereas in an osteoarthritis of the knee study patients may be uncomfortable for a time, but are not at risk of a life-threatening or permanent health rpoblem.

To help ensure that patients know the risks and benefits of enrolling in a study, each participant must sign an "informed consent" form, which explains in simple language:

• the purpose of the study
• what volunteers will be asked to do (take a pill twice a day for three months, for example, and visit the doctor once a week for blood and other laboratory tests)
• the possible benefits and known adverse reactions associated with the experimental treatment
• other therapies that are available alternatives for their condition.
• other benefits such as stipends paid for travel expenses

Once a patient volunteers for a study, the responsibility of monitoring the patient’s well-being doesn’t stop there. As a study progresses, researchers follow the patient closely so if major positive or negative drug effects are seen, the study can be stopped. Also, a patient can drop out at any time during the study for whatever reason.

Still, the use of placebo-controlled trials is controversial. Some people oppose the use of placebo-controlled studies in almost all drug research.

Others feel the need for placebo-control to truly assess a drug’s worth- to know for sure what is effective and what is not- are crucial to developing better treatments. In conditions like arthritis, it is important to use placebo control because of the nature of the illness where there are good days and bad days that occur irrespective of treatment.