Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine (PDQ®): Complementary and alternative medicine - Health Professional Information [NCI]
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Levels of Evidence: Cancer CAM Human Studies
A classification system has been developed by the National Cancer Institute's PDQ Adult Treatment Editorial Board to allow the ranking of human cancer treatment studies according to statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. This classification system has been adapted to allow the ranking of human studies of complementary and alternative medicine treatments for cancer. The purpose of classifying studies in this way is to assist readers in evaluating the strength of the evidence associated with particular treatments. However, not all human studies are classified. Only those reporting a therapeutic endpoint(s), such as tumor response, improvement in survival, or measured improvement in quality of life, are considered. In addition, anecdotal reports and individual case reports are not classified because important clinical details are often missing, the evidence from them is generally considered weak, and there is an increased probability that similar results (either positive or negative) will not be obtained with other patients. Furthermore, reports of case series are excluded when the description of clinical findings is so incomplete as to hinder proper assessment and interpretation.
Strength of Study Design
In the classification system, a numeric scale from 1 to 4 is used to indicate the statistical strength of the study design, with 1 assigned to studies having the strongest design and 4 assigned to studies having the weakest design. Further subdivision of some design categories yields finer measures of strength. The various types of study design are described below in descending order of strength:
|1.||RANDOMIZED CONTROLLED CLINICAL TRIALS: Studies in which participants are assigned by chance to separate groups for the comparison of different treatments. It is the patient's choice to be in a randomized trial, but neither the researcher(s) nor the patient can choose the group in which he or she will be placed. Using chance to assign people helps to ensure that the groups will be similar and that the treatments they receive can be compared objectively. At the time of a trial, there is uncertainty about which of the treatments is best. These trials can be "double-blinded" or "nonblinded." Double-blinded trials have a stronger study design.
|2.||NONRANDOMIZED CONTROLLED CLINICAL TRIALS: Studies in which participants are assigned to a treatment group based on criteria that may be known to the researcher(s), such as the patient's birth date, chart number, or day of clinic appointment. With this type of study design, there is less confidence that the group receiving the treatment under study and the control group are comparable.|
|3.||CASE SERIES: Studies that describe results from a group or series of patients who all received the treatment that is being investigated. These studies have a weak design, due, in part, to the absence of a control group. Different types of case series, in descending order of strength, are as follows:
|4.||BEST CASE SERIES: From a larger series of patients, only the cases that appear to have benefited from the treatment under study are reported. These studies have the weakest design.|
Strength of Endpoints Measured
The scientific strength of a study's findings is determined by the endpoint(s) measured. In the classification system, a progressive alphabetic scale is used to indicate the scientific strength of endpoints, with the letter A assigned to the strongest endpoint that can be measured and the letter D assigned to the weakest endpoint. Commonly measured endpoints in human cancer treatment studies are listed below in descending order of strength:
|1.||TOTAL MORTALITY: The proportion of the study population that died. Frequently called the death rate. Measured from a defined point in time, such as the time of diagnosis or the time since treatment was initiated. This is the most easily defined and objective endpoint. The inverse of total mortality, i.e., overall survival, may be the reported value.|
|2.||CAUSE-SPECIFIC MORTALITY: Death from a specified cause in the population under study, for example, death from cancer versus death from side effects of therapy versus death from other causes. This endpoint is more subjective than total mortality. When death from disease (e.g., cancer, heart disease, etc.) is the measured endpoint, the inverse value, i.e., disease-specific survival, may be reported instead.|
|3.||CAREFULLY ASSESSED QUALITY OF LIFE: Although a very subjective endpoint, quality of life is an extremely important endpoint to patients. The strength of a quality of life assessment depends on the validity of the instruments (i.e., questionnaires, psychologic tests, etc.) used.|
|4.||INDIRECT SURROGATES: These are measures that substitute for actual health outcomes, and they are subject to investigator interpretation. In descending order of strength, indirect surrogates include the following:
Combined Level of Evidence Score
A combined level of evidence score is calculated for each qualifying study—except for Best Case Series—by joining the score for statistical strength of study design with the score for strength of the endpoint(s) measured. Because of their extremely weak study design, Best Case Series are given a score for strength of study design only (i.e., a level of evidence score of 4). The level of evidence scores for the remaining study types range, in decreasing order of strength, from 1iA to 3iiiDiii.
ADDITIONAL INFORMATION ABOUT CAM THERAPIES
- The National Center for Complementary and Alternative Medicine (NCCAM).
- The National Cancer Institute Office of Cancer Complementary and Alternative Medicine (OCCAM).
- CAM on PubMed, a special subset of the PubMed scientific literature database created through a partnership between NCCAM and the National Library of Medicine.
- PDQ® - NCI's Comprehensive Cancer Database
Full description of the NCI PDQ database.
OTHER PDQ SUMMARIES
- PDQ® Cancer Information Summaries: Adult Treatment
Treatment options for adult cancers.
- PDQ® Cancer Information Summaries: Pediatric Treatment
Treatment options for childhood cancers.
- PDQ® Cancer Information Summaries: Supportive and Palliative Care
Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
- PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
Tests or procedures that detect specific types of cancer.
- PDQ® Cancer Information Summaries: Prevention
Risk factors and methods to increase chances of preventing specific types of cancer.
- PDQ® Cancer Information Summaries: Genetics
Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
- PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
Information about complementary and alternative forms of treatment for patients with cancer.
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Date Last Modified: 2002-10-02