Wednesday, July 16, 2008

Neoplasms: 9

This is the ninth blog in a series of blogs on neoplasia.

In the past few blogs, I've been trying to explain the disconnect between cancer survival data and cancer death rate data. The cancer survival data seems to indicate that we're making enormous improvements in cancer treatment. The cancer death rate indicates that Americans are dying from cancer at about the same rate as they had been a half-century ago.

Several days ago, I listed over a dozen biases in cancer survival data that contribute to an overly optimistic sense of medical progress.

In this and the next few blogs, I thought I'd review some of these biases. The purpose of this exercise is to explain that the interpretation of survival data is enormously complex and that survival data is probably not the best way to gauge progress in the field of cancer research.

Today, let's look at population and demographic biases.

For many different reasons, some populations accrue more easily into clinical trials than other groups. Most notorious are children and pregnant women. Many clinical trials have no children and no pregnant women. Under such conditions, drug effectiveness and safety cannot extend to these groups. Third party payers may refuse to cover the costs of drugs for pregnant women and children due to lack of any trial evidence indicating that the drug is safe and effective in these groups.

Demographic bias is a variant of population bias. In most clinical trials in the U.S., patients are assigned broad demographic groups, and the patients are often allowed to assign themselves into groups based on the group to which they have the closest social identity. Treatment response rates that may differ from group to group and for unaccounted subgroups within a single group (e.g., Japanese patients may have a different response from Chinese patients).

In clinical trials, groupings are usually based on stage of disease and age. Seldom do clinical trials stratify patients by income. Nonetheless, socioeconomic status greatly influences cancer survival [1]. Groups that contain many economically disadvantaged patients are likely to have a shorter survival than similar groups where the members are financially well-off.

Population bias effects every population that is not included in study populations. A good examples comes from our interpretation of PSA (prostate specific antigen) values in men. PSA is the most important screening test for prostatic cancer. PSA levels less than 4 indicate low risk of prosate cancer. PSA levels greater than 4 indicate high-risk patients and prompt a diagnostic study. The clinically accepted ranges of PSA levels were adapted from data collected from a community-based Minnesota population consisting entirely of white men [2]. In discussing the importance of age-specific ranges, the Mayo Clinic group acknowledged that African African-Americans and Asians were omitted from their study [3].

Does the screening criteria, developed for normal PSA ranges in a white population, fit the normal ranges for African-Americans and Asians? In a review of PSA levels among white men and black men, conducted by Sawyer and coworkers, studying 30,000 PSA values collected for about 3,000 subjects, it was shown that African-Americans have a higher range of PSA levels than do white Americans [4]. A separate study of PSA levels in Asian men found a lower range of PSA levels in this population [5].

1. [Gorey KM, Holowary EJ, Fehringer G, Laukkanen E, Moskowitz A, Webster DJ, Richter NL. An international comparison of cancer survival: Toronto, Ontario, and Detroit, Michigan, metropolitan areas. Am J Public Health 87:1156-1163, 1997.]

2. [Oesterling JE, Jacobsen ST, Chute CG, Guess HA, Girman CJ, Panser LA, Lieber MM. Serum prostate-specific antigen in a community-based population of healthy men. JAMA 270:860-864, 1993.]

3. [Oesterling JD, Jacobsen SJ, Cooner WH. The use of age-specific reference ranges for serum prostate specific antigen in men 60 years old or older. J Urol 153:1160-1163, 1995.]

4. [Sawyer R, Berman JJ, Borkowski A, Moore GW. Elevated prostate-specific antigen levels in black men and white men. Modern Pathology 9:1029-1032, 1996.]

5. [Oesterling JE, Kumamoto Y, Tsukamoto T, Girman CJ, Guess HA, Masumori N, Jacobsen SJ, Lieber MM. Serum prostate specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men. Br J Urol 75:347-352, 1995.]

-Copyright (C) 2008 Jules J. Berman

key words: cancer, tumor, tumour, carcinogen, neoplasia, neoplastic development, classification, biomedical informatics, tumor development, precancer, benign tumor, ontology, classification, developmental lineage classification and taxonomy of neoplasms

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