Placebo (pl·sēˑ·bō)

n 1. inert substance used in control groups of clinical studies to maintain blinding.

Q. How can the design of a clinical trial address some of the ethical concerns around using placebos?

A: Placebos should be used in cancer clinical trials only when

(1) it is scientifically necessary,

(2) ethically appropriate,

(3) and when patients have been clearly informed that they will receive a placebo and whether they will receive the active drug at some point during the clinical trial, if not immediately.

Use of placebo controls may be justified in these situations:

To prove effectiveness of a new treatment for diseases with high placebo response rates

In conditions that alternately become worse or better, have spontaneous remissions (the disappearance of the signs and symptoms of cancer, but not necessarily the entire disease), or have an uncertain and unpredictable course

When existing therapies are minimally effective or have serious side effects

In the absence of any effective therapy

Furthermore, patients randomly assigned to a placebo must not be substantially more likely than those in active treatment group(s) to: die; suffer irreversible illness, disability, or other substantial harms; suffer reversible but serious harm; or suffer severe discomfort.

Thus, placebo-controlled trials should also ensure that patients receive outstanding supportive care during their participation in the study. Specific clinical trial designs can be used to minimize the chances that a patient receives a placebo. For example, the clinical trial may permit crossover to the active drug at the time of disease progression, which is the point at which the cancer continues to grow or spread. In such clinical trials, all patients have the opportunity to receive the new treatment, although some receive it sooner than others do.

Q. What are some examples of when it is not appropriate for a person with cancer to participate in a placebo-controlled trial?

A: Placebo-controlled trials are never appropriate when a highly effective or potentially curative therapy is available for a patient. An exception is unless the trial allows the patient to receive the new treatment/placebo in addition to the potentially curative therapy. For example, let’s say that a promising new treatment is in development for advanced testicular cancer, a disease that is curable in many cases with the use of chemotherapy. It would not be appropriate for a clinical trial to randomize patients between the new treatment and placebo because potentially curative chemotherapy already exists. However, it might be appropriate to randomize between standard chemotherapy plus the new drug or standard chemotherapy plus placebo because in both cases, patients will receive the standard, potentially curative treatment.

Q. What questions should patients ask their doctor about placebo-controlled clinical trials?

A: The main questions that patients should ask are about their treatment options. If a patient has already received all known, effective therapies for their disease, options may include supportive care or participation in a clinical trial. If participation in a clinical trial is an option, patients should understand the rationale and goals of the trial, whether it involves use of a placebo, and the likelihood of receiving the drug being studied or a placebo.

It is also important to ask about the likelihood of benefit from the investigational treatment and the potential side effects. If a placebo is administered as part of the trial, patients should ask whether there will be an opportunity to receive the study drug at any point in the trial, if not immediately upon enrollment.

PMID: 16109176 Owner: NLM Status: MEDLINE

Abstract/OtherAbstract:

BACKGROUND AND PURPOSE: Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability.

METHODS: We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks) to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out.

RESULTS: We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p < .001). A multiple regression model explained 79% of the variance in placebo variability (F = 59.7; p < 0.0001). Significant predictors are, among others, the duration of the study (beta = .31), the quality of the study (beta = .18), the fact whether a study is a prevention trial (beta = .44), whether dropouts have been documented (beta = -.20), or whether additional treatments have been documented (beta = -.17). Healing rates with placebo are lower in the following diagnoses; neoplasms (beta = -.21), nervous diseases (beta = -.10), substance abuse (beta = -.14). Without prevention trials the amount of variance explained is 42%.

CONCLUSION: Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated.