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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers Ethical and Legal Issues Relating to the Inclusion of Asian/Pacific Islanders in Clinical Studies Elena S. H. Yu A precise count of Asian and Pacific Islander Americans (APIAs) is lacking. According to the 1990 Census, the official count of APIAs is only 7.3 million. However, according to the Healthy People 2000 report (U.S. Department of Human Services, 1990), there are more than 11 million APIAs. Regardless of what the number is, the consensus exists that APIAs are the fastest growing ethnic minority in America, followed by Hispanics. Between 1980 and 1990, they increased by 108%, with California surpassing the national rate and growing by 127%. Indeed, every state except Hawaii sustained a growth rate of at least 40%. The slower rate of increase in Hawaii (17%) is attributable to the fact that the Asian/Pacific Islanders represent three-fifths of the population in that state. Already, immigrants from Asia on average form about 45% of all immigrants entering the United States annually. Despite this phenomenal increase, APIAs remain the most underresearched and the least understood ethnic minority in America. The purpose of this paper is to complement some of the points made in the paper by Gamble (1994) and to present an Asian/Pacific Islander minority perspective to the ethical and legal issues of including APIA populations in clinical studies. A description of the APIA population is presented below, followed by a general overview of the sources of epidemiologic and health data on this special ethnic minority. Next, several conceptual and methodological issues are identified and discussed. They include: (1) problems in the definition of the study population; (2) the myth of a healthy minority; (3) lack of baseline epidemiologic data on ethnic subgroups; (4) dissemination of information from existing studies; and (5) the issue of informed consent. Implicit in these
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers discussions is the need to empower APIA minority investigators in research, in order to foster cultural sensitivity in research and to ensure that the objectives of clinical studies will benefit both minority and majority populations alike. DESCRIPTION OF THE POPULATION The term Asian/Pacific Islander Americans encompasses at least 45 ethnic groups. Nationally, Asian Americans make up about 95% of the APIA population and Pacific Islanders about 5%. Among Asians, Chinese and Filipinos—with about 1.6 and 1.4 million members, respectively—are the two largest subpopulations, comprising 23% and 19% respectively of the total APIA population. They are followed by the Japanese (12%), Asian Indians (11%), and Koreans (11%), each numbering near or over 800,000. Vietnamese form the smallest percentage (8%) of the six major APIA subgroups. Insofar as the Pacific Islander populations are concerned, Hawaiians are the largest group, with over 200,000 persons, followed by the Samoans and Guamanians (63,000 and 49,000, respectively), and then by Tongans and Fijians, who number less than 20,000 and 10,000, respectively. Unique Characteristics of the APIA Population In 1990, a majority of the APIAs resided in just three states: California, New York, and Hawaii. Seventy-nine percent of all APIAs may be found in 10 states (California, New York, Hawaii, Texas, Illinois, New Jersey, Washington, Virginia, Florida, and Massachusetts). More detailed information from the 1990 Census by ethnicity for the APIAs is not yet available. What little aggregate demographic data that exist point to the following conclusions. Within this special population, some ethnic groups, such as Japanese Americans, are reported to have annual family incomes 38 percent higher than the national median income (APPCHO, 1993). Other groups, such as Laotian immigrants, have one of the highest poverty rates of any group in the nation (U.S. Department of Human Services, 1990). These family income data obscure the fact that Asian Americans and Pacific Islanders have larger numbers of family members living together than the general U.S. population and that it is a cultural practice to pool the income of household members in order to cover family expenses. There are several other unique characteristics about this special population. First, they are geographically concentrated and yet widely dispersed. Some 58.5% live in the Western regions of the United States, 17.4% live in the Northeast, 13.8% live in the South, and 10.3% live in the Midwest. About 45% of the APIA population live inside central cities, compared with 25% of the white American population. Only 6% of the APIAs live in nonmetropolitan
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers areas, compared with 24% for white Americans. However, within the continental United States, APIAs represent less than 10% of the total state population of California and even smaller percentages in the remaining 9 states with the largest APIA population. This special population is also predominantly foreign-born rather than U.S.-born. As a result, a significantly large percentage of the population do not speak English fluently. Many are linguistically isolated—defined as the absence of any household member, 14 years and older, who can speak English. SOURCES OF EPIDEMIOLOGIC AND HEALTH DATA Health and epidemiologic data on APIAs are severely limited for a number of reasons, such as: (1) many research data, including those collected by the federal government, on APIAs cannot be further stratified by ethnic groups; (2) where the data have been coded to identify specific ethnic groups, as in the U.S. vital statistics records, the number of groups that can be identified are limited only to the older immigrants or Pacific Islander populations [changes are now being introduced by the National Center for Health Statistics (NCHS) to expand the codes for the APIA subgroups]; (3) local or regional studies of Asian Americans and Pacific Islanders are very few and seldom published in widely accessible journals. These studies limit generalizability because of the profound diversity within APIA populations. Consequently, we know little about the health problems of APIAs other than those that have been commonly reported for some time. We know from Healthy People 2000 that: the breast cancer incidence rate among Native Hawaiians is 111 per 100,000 women, as compared to 86 per 100,000 among whites. The lung cancer rate is 18 percent higher among Southeast Asian men than for the white population. And the liver cancer rate is more than 12 times higher among Southeast Asians than in the white population. Higher rates of high blood pressure have been found among Filipinos aged 50 and older living in California than among the total California population. We also know from the California data that the leading causes of death for Asians and Pacific Islanders are: heart disease (28%), cancer (24%), stroke (9%), injuries (79%), pneumonia/influenza (4%), chronic lung disease (3%), suicide (2%), diabetes (2%), perinatal conditions (2%), and liver disease (1%). Tuberculosis and hepatitis B are the two major infectious diseases that afflict large segments of the APIA population. Smoking is the single most significant "lifestyle" factor that poses a threat to their health. Among the California immigrant groups, smoking rates among men are 92% for Laotians, 71% for Cambodians, and 65% for Vietnamese compared to 30% for the overall
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers American population. Moreover, since an overwhelming majority of the immigrant groups are foreign-born, linguistic and cultural issues are persistent barriers to health care as well. The increasing economic power of the Pacific Rim countries and the shift in U.S. funding policies towards supporting more studies on under-studied populations, such as women and minorities, mean that Asian Americans and Pacific Islanders have finally become the new frontiers of research explorations when they have been a historically ignored subject pool in past studies. The interest in Asian Americans and Pacific Islanders as a potential source of study subjects comes at a time when medical and public health professions are advocating for more clinical trials. The benefits to mankind and to the scientific community of being able to do research in experimentally controlled settings are obvious. Unfortunately, a number of factors—such as the historical backgrounds of Asian/Pacific Islanders' immigration to the United States, the sociocultural contexts of their medical manpower development, and the past history of medical research in Asia and the Pacific Islands, significantly affects how individuals in this special population will perceive and interpret the new research emphasis. Lack of knowledge about how to define and identify the different subpopulations of APIAs, ignorance of the morbidity risks of this ethnic minority, and lack of baseline epidemiologic data also severely constrain the scientific justification for clinical studies, especially clinical trials. Historical Factors and Manpower Development From 1882, when the Anti-Chinese Exclusion Act was passed to prevent Chinese from entering the United States and becoming citizens, to the Gentlemen's Agreement of 1906 that curbed Japanese immigration, and the 1924 Immigration Act prohibiting the entry of "aliens ineligible for citizenship"—which included the entire Asia-Pacific basin all the way to Greece—up until 1965, Asian/Pacific Islanders have been systematically treated as less desirable than white Europeans. Today, despite the impressive academic achievements of Asian Americans in SAT-quantitative tests at the high school level (they perform poorly on the SAT-English tests, which is seldom noted by the media), and despite alleged "overrepresentation" of Asian Americans in medical schools, few Asian Americans and even fewer Pacific Islanders have made it into medical research fields. The small numbers cannot possibly be merely a random process when one takes into consideration the size of the denominator or population of Asian Americans who completed medical training or have a Ph.D. degree in public health, compared to other ethnic groups. We know from diverse sources that between 1973 and 1992, the representation of APIAs among all applicants to medical schools increased from 1.3 percent to
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers 16.5 percent (Association of American medical Colleges, 1993). Among those who applied to medical schools, acceptance rates for Asian Americans have ranged from a low of 28 percent during the 1974–75 academic year to a high of 63.4 percent during the 1988–89 academic year, and now are 50.6 percent for the 1991–92 academic year. Between 1977 and 1992, the number of APIAs enrolled in medical schools increased from 1,422 to 9,438, or from 2.4% to 14.4%. In terms of medical school graduates, the number is smaller. Available data showed that only 378 APIAs graduated from medical schools in the 1978–79 academic year, and by 1990–91 that number increased to 1,687. Still, the percentage of APIAs who graduated from U.S. medical schools has increased significantly during these two periods, from 2.6% of total graduates in 1978–79 to 10.9 percent of total graduates in 1990–91 (Gall and Gall, 1993). These figures do not include graduates of schools of public health, for which data are not available. Not with-standing the large numbers of Asian Americans who completed M.D., D.Sc., or Ph.D. degrees, few made their careers in academia or in research as principal investigators (PIs) of large projects. They often appear as research associates or as technical experts, rarely as co-PIs, thereby having very little impact on broad health policy decisions. Thus, the medical research profession itself, being historically dominated by mainstream white-American investigators, now has a new mission—to increase the participation of women and minorities as subjects in clinical trials. Does any Asian/Pacific Islander have any problem with that? Factors Affecting Data Interpretation in Clinical Trials In the process of designing and conducting clinical trials, a number of factors which affect the interpretation of data need to be fully articulated. This author considers the following issues important. Definition of the Study Population The term Asian Americans and Pacific Islanders covers a myriad of cultures and at least 45 linguistic groups whose ancestries can be traced to places that include Mongolia to the north, the islands near Australia to the south, India and Pakistan to the west, and Hawaii to the east. In terms of skin color, this population consists of a full-range of ''colors,'' ranging from "black" to "brown," "yellow," and "white." For example, the Spaniards who have settled in the Philippines and who considered themselves Filipinos are "white" by skin pigmentation, while the Spanish mestizas who are of mixed parentage may be of any mix of colors. No existing racial classification schemes can possibly identify
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers the members of this population into only one racial stock or gene pool. In their native habitats, some are nomads living on horseback; others ride the "bullet trains" that even the United States does not have; and still others go to work in chauffer-driven Rolls Royces. In terms of indigenous diet, some are vegetarians, others shun pork, while still others do not eat beef. Suffice it to say that they differ immensely in terms of racial origin, religion, lifestyle, diet, and health. How does one scientifically define this special population in any piece of epidemiologic and clinical research? What should one use as the criteria for determining whether someone is an Asian/Pacific Islander or a member of a subgroup of its populations, such as Chinese, Japanese, Filipinos, Hawaiians, Samoans, Guamanians or others? Should the definition be based on ancestry? Self-definition of ethnicity? Or interviewer observation of "race," as has occurred in several government surveys prior to 1976? And how should one ''treat" or interpret findings of ''racial" differences between white and APIA populations? Unless these basic conceptual issues are handled carefully, any clinical study which reports data for APIAs without additional breakdowns by ethnicity is subject to distortions and misinterpretations. Definitions based on "race" may be useful in research on genetics and disease (if a consensus can be reached on the validity and reliability of any existing "racial classification" systems), but the same classification system may not be useful if the critical determinant of health or disease is in fact lifestyle and not genes. In the latter case, being able to classify the study subjects in terms of their ethnic group identity may be preferred to "race," for the former would shed light on the group membership and normative lifestyles of the study subjects that may be salient in explaining a particular health outcome. The Myth of a Healthy Minority Due to lack of research and inadequate information, findings from available studies on APIAs may have unwittingly sustained the myth —begun in the 1960s—that Asian Americans are quite healthy compared with black or white Americans. The best known investigator-initiated studies of Asian Americans conducted in Hawaii and California are "migrant studies"—which are by nature comparative. Typically, a specific population—usually the Japanese—are sampled in three locations (e.g., Japan, Hawaii, and California) and compared, or they are studied in two locations (e.g., Japan and Hawaii, or Japan and California) and then compared to white Americans. Using similar study designs and questionnaires to the extent possible, inferences are drawn about the health status or morbidity patterns of the Japanese as an example of Asian/Pacific Islanders. While logically sound, an unintended consequence of this approach is to use the most established Asian American subgroup—which happens to have
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers an extremely large percentage of English speakers and also the highest socioeconomic attainment of all Asian Americans—to represent the APIAs—an ethnic minority characterized by a heavy representation of persons from low socioeconomic status and nonnative English speakers. Thus, it is easy for both the media and policymakers to gloss over the issue of ethnic diversity in health and morbidity. Furthermore, comparisons between the Japanese and white Americans have often led to the conclusion that the Japanese are in "better" health than white Americans. They may have inadvertently buoyed the myth of Asians as a healthy minority, at the expense of rigorously controlling for social class or socioeconomic status—a key variable in any health study. In several epidemiologic studies of Asian subgroups, social class or socioeconomic status have often been poorly measured, even if they can be and have been properly "controlled for" statistically. Consequently, the general public or mainstream researchers are not always aware that the other APIA subgroups are very much unlike the Japanese Americans. Often, use of the term APIA confers a myth of cultural and racial homogeneity, which in turn gives the appearance of scientific validity when in fact the numbers of specific APIA subgroups included in past population-based studies conducted in the United States have been extremely small to the point of being insignificant and unanalyzable. Yu and Liu (1992) have noted that our knowledge of the health risks and morbidity patterns of different Asian/Pacific Islander subgroups in the United States have been drawn primarily from the following general sources of data: (1) investigator-initiated epidemiologic surveys conducted in Hawaii and at the West Coast, such as the migrant studies described above and other types of studies (Curb et al., 1991; Kagan et al., 1974; Kato, Tillotson, Nichaman, Rhaods, and Robertson et al., 1977; Stavig, Igra, and Leonard, 1984; Stemmermann, Chyou, Kagan, Nomura, and Yano, 1991; Takeya et al., 1984; Tillotson et al., 1973; Yano and MacLean, 1989; Yano, Reed, Curb, Hankin, and Albers, 1986); (2) Surveillance, Epidemiology and End Results (SEER) cancer registry data maintained in selected cities (Hinds, Kolonel, Lee, and Hirohata, 1980; Kolonel et al., 1981; Yu, 1986); (3) descriptive clinic-based studies, such as the Kaiser Permanente Prepaid Health Plan (Angel, Armstrong, and Klatsky, 1989; Klatsky and Armstrong, 1991); and (4) mortality statistics compiled by the National Center for Health Statistics (Haenszel and Kurihara, 1968; King, 1975; Kleinman, 1990; Li, Ni, Schwartz, and Daling, 1990; Liu and Yu, 1985; Lynberg and Muin, 1990; Yu, 1982). There have been extremely few clinical studies, much less clinical trials involving APIAs. Of the few that exist, most are focused primarily on pharmacologic reactions. Usually, only one subpopulation is studied, although the word "Asian" may be used in the reports, thereby giving the false impression of validity and generalizability to the entire APIA population. This quantum jump in logical inference from one subgroup to "all" Asian/Pacific Islanders should be avoided. Instead, the subpopulation should be
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers specifically identified. Lack of Baseline Epidemiologic Data on Ethnic Subgroups In the absence of alternative data sources, continuing use of the existing data and implicit acceptance of their methodological approaches have had at least two negative consequences: (1) a slower rate of development of knowledge about the morbidity risks more commonly encountered in Asian/Pacific Islander subgroups than in the majority white population; and (2) a general lack of baseline data on Asian/Pacific Islander ethnic groups and health status. As scientists continue to use the prevailing morbidity risks of white or black Americans as the basis for research, scientific and public awareness of more troubling Asian American health risks (e.g., tuberculosis and hepatitis B, stroke and diabetes) remained low until the media recognized that these diseases are affecting the mainstream populations at an alarming rate. What are the common diseases that Asian/Pacific Islanders experience besides the ones listed above? Will the informed APIA investigators succeed in drawing attention to the importance of studying diseases that might be more prevalent and have a higher incidence in their ethnic communities than in the mainstream society? And will their effort to study ethnic-specific diseases be encouraged through grant awards or will we continue to study diseases that are epidemiologically far more common in, or which have a greater impact on, the mainstream population than in the APIA communities? The most fundamental problem with the new push to include APIA population in clinical trials is the near total absence of a descriptive database about these vulnerable populations that could provide a scientific basis for their inclusion. Clinical studies, and specially clinical trials, by design involve far more risk than mere descriptive surveys. The potential for ethnic misunderstandings is great because the scientific community, which is predominantly white, and which previously showed lack of interest in collecting descriptive epidemiologic data on the APIA populations, now encourages the inclusion of minorities in their clinical trials. Progress in research has no doubt been made, but nagging questions will continue to haunt us. Questions such as: Why is it not important to collect baseline data on these underresearched populations? Who would benefit most from clinical studies—the majority population or the minorities? Which diseases or health conditions are targeted for clinical trials? Are there diseases that afflict the APIA populations in strikingly larger proportions than the mainstream U.S. populations (e.g., cancer, stroke, atherosclerosis, thinness in some subpopulations and obesity in other groups, normal cholesterol levels but abnormal triglycerides)? Or are there health conditions which impact more severely on the mainstream white
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers populations than on the APIA minorities, in terms of proportional mortality? Who decides what specific diseases should be studied in clinical trials? Who benefits the most from these clinical studies? What is the ethnic composition of the peer review committees who approve the grant applications for clinical trials? To what extent have ethical criteria been incorporated into the peer review process? The invasiveness of clinical trials, compared to what are known as "observational studies" in epidemiology or population-based door-to-door survey types of research in the social sciences, raises the spectre of mass experimentation and highlights the dispensability of the APIA population. The existing poverty in many subgroups of APIAs will make them exceedingly vulnerable to the temptations of submitting themselves as human subjects for clinical trials in exchange for monetary rewards. Often, offers of $200 to $800 payments, fairly common in clinical trials that involve the collection of biological specimens, far exceed the one-month take-home pay of individuals living in poverty. Because of this, the issue of informed consent in vulnerable populations must be deliberated, and the legal liability and moral responsibility issues must be studied carefully. Should legal liabilities not extend a lifetime when the effects of some drugs, such as steroids and hormones, might be life long? How do we determine what is the appropriate length of follow-up for clinical trials? How do we clarify the moral responsibility of researchers to keep their subjects informed of their research findings? Who owns the clinical data collected by the investigators? Moreover, how do we ensure and enforce informed consent in clinical trials? Dissemination of Information from Existing Studies A few studies have been conducted on Asians and Pacific Islanders in their home countries as part of the U.S. involvement in the Pacific theatre or as a consequence of its foreign policies. But findings from such studies are not widely known, even though they have been reported in peer-reviewed journals. For example, some of the U.S. military's activities and observations of Pacific Islanders are widely known to the public only through coverage by the media. CBS, for instance, once broadcast (on 60 Minutes, CBS Television Network, July 13, 1980) that the U.S. government had conducted 43 separate nuclear explosions mainly on the Pacific atoll of Eniwetok, which consists of 41 named islands and is part of the now independent Marshall Islands. These nuclear events resulted in serious contamination with plutonium, strontium, cesium, and other dangerous substances on the northern islands of Eniwetok where the bombs were exploded. The inhabitants were relocated to another island. Six inches of contaminated topsoil and tons of radioactive metal from
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers test towers were removed bargeload by bargeload, to be buried in one island called Runit, making the latter off limits for the next 24,000 years. The clean-up has theoretically removed the plutonium; but beneath the plutonium-free soil, "there is still cesium and strontium and one or two other elements that are hazardous to your health" (CBS News, 1980:14). The Eniwetok explosion is similar to an earlier U.S. bombing experience on Bikini Island, which has provided ample evidence that local vegetations, such as coconuts, continue to contain high levels of cesium and strontium, despite any nuclear clean-up efforts. The inhabitants who returned to live on Bikini Island showed high traces of plutonium in their bodies and run a high risk of getting cancer. Hence, they had to be removed once again from the island and are "forever wards of the United States" (CBS News, 1980). But, when the people of Eniwetoks demanded to return to their native land, the U.S. military facilitated their return. A dose assessment team was assembled by the United States, presumably to inform the inhabitants "who've never seen an electric light bulb'' about the risks of living on the contaminated atolls. It was clear from the 60 Minutes report that the U.S. military kept good records of the Bikini Island inhabitants and intended to do the same with the Eniwetok islanders. But has the scientific community been able to evaluate these data? And did the inhabitants of the affected atolls really know what had taken place in their lives? Can a population with about a fourth-grade level of education and one that lives in a subsistence economy have informed knowledge about the devastating long-term impact of radiation on human physiology and functioning? Is this or is this not "natural'' experimentation with human subjects conducted under the guise of "humanitarian" clean-up efforts and medical "follow ups"? The above questions attain a certain degree of significance when one considers that the first human subjects to be used in the testing of the effectiveness of the pill as a method of contraception were poor women in Puerto Rico during the early 1960s. Poverty was the social and ethical justification for selecting Puerto Rican women into the early trials on the effectiveness of the pill as a contraceptive device. By the late 1970s, we would learn from scientific studies conducted in the People's Republic of China that the dosage of specific hormones in the pill produced in the United States were "unnecessarily high." Now, of course, we also know the potential adverse impact of these hormones on the development of certain types of diseases (e.g., thromboembolism). But where are the poor Puerto Rican women now who were the human subjects for the clinical studies of the "pill" 20–30 years ago? Given the current knowledge that the latency period for some diseases may be more than 10 years—some may be 20 years or longer—did the clinical trials on the pill in the 1960s play an important role in the reportedly high incidence of many diseases among Puerto Rican women today? There was a legal reason for choosing Puerto Rico as the site for U.S. clinical studies (it was part of the United States and yet some U.S. laws on drug testings did not apply to the island). What is the legal liability of
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers the investigators to the Puerto Rican subjects 20 years or more after the clinical trials have been completed? Few pharmaceutical companies run their clinical trials over a long period of time. Rather, the trials are cut off as soon as a particular "positive" or "beneficial" effect has been "substantiated'' by an acceptable p-value. This deliberate cut-off of the length of observation in clinical studies, prompted no doubt by the twin forces of funding constraints and pressure to market a new drug, means that the long-term effects of many drugs tested in clinical trials remain unknown. The moral responsibility to make a drug available to the public as soon as it is found to be effective in the treatment of a disease must be balanced by the moral obligation to establish built-in follow-up procedures over a long-term period in order to determine unanticipated side effects or to monitor the subjects' health on a continuing basis. Now, does the absence of knowledge about the long-term effects of a drug or surgical procedure justify the absence of medical and legal measures to follow-up the subjects for life? As Puerto Ricans become more aware of their rights, will other territories under U.S. possession located in the Pacific Ocean become even more convenient sites for many risky clinical trials involving human subjects? In the context of these concerns, the Institute of Medicine's effort to understand the legal and ethical issues of including Asian and Pacific Islanders in clinical trials is commendable. In what follows, we discuss the problems of obtaining informed consent from Asian Americans and Pacific Islanders, leaving aside the issue of legal liabilities because of lack of expertise on this subject. The Issue of Informed Consent The concept of informed consent, adopted by the USPHS in medical experiments only in 1966, refers to a person's ability to consent freely to participate in a study in which he or she adequately understands both what is required and the "cost" or risk for participating in the study (Wolfensberger, 1967). On July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law, thereby creating the National Commission on the Protection of Human Subjects of Biomedical and Behavioral Research. The latter produced the Belmont Report (U.S. Department of Human Services, 1979), which identifies the basic ethical principles for research with human subjects and established guidelines which should be followed to assure that such research is conducted in accordance with those principles. The Public Health Service Act, as amended by the Health Research Extension Act of 1985 Public Law 99-158 (November 20, 1985) specifies the details for the establishment of Institutional Review Boards at institutions where research on human subjects are to be conducted. The Code of Federal Regulations, Title 45, Part 46 (U.S. Department of Human Services, revised June 18, 1991), further spells out the meaning of
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers informed consent, the types of research requiring informed consent, and the kind of information that is required to establish informed consent. These successive instances of legislation provide evidence of formal and legal protection of human subjects in research. However, how these laws are implemented in the informal context of everyday life is far from clear. Yu and Liu (1986) pointed out that under normal conditions and with Americans who have had more than 40 years of exposure to polls, surveys, and clinical trials, the task of obtaining informed consent is a routine procedure. But in dealing with special populations such as the poor, the uneducated, and recent immigrants and refugees from Asia and the Pacific Islands, chances are great that for one reason or another, a sizable number are unable to absorb the information necessary for them to meaningfully grant informed consent, even where the interviewers are "racially" matched with the study subjects (Hurh and Kim, 1982). The problem of informed consent is more serious among the APIA population than among black Americans in the sense that many Asians and Pacific Islanders, being predominantly foreign-born, lack a general idea of what their basic human rights are in this country. For a large majority, freedom of political expression never existed in their country of origin. Some segments of the population, particularly older women, are least able to express themselves, assert their rights, or ask questions (Yu and Liu, 1986:487). Not having been included often enough as subjects in the major descriptive epidemiologic studies in the United States, APIAs are naturally unfamiliar with the expectations and procedures, promises, and limitations of medical and public health research. Several investigators have noted, though not published, their observations that some APIA study subjects will sign their name because the source that asked them to do so is credible and not because they understand what was asked of them or the risks involved. A credible source includes such individuals as professors or doctors, who, in traditional APIA cultures are revered and cannot be questioned. To date, there has not been any systematic study of how APIAs understand the process of informed consent in research in general, or in specific types of studies such as survey interviews versus clinical trials. The high illiteracy rate among older APIA women means that even when the informed consent form is written in their native non-English language, a significantly large number of them will still not be able to understand the words they see nor can they sign their name. Will majority and minority investigators be trained in the ethics of obtaining informed consent from such "vulnerable" populations? How will the regulations for ensuring informed consent be enforced?
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Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, Volume 2 - Workshop and Commissioned Papers DISCUSSION In a nutshell, a lack of baseline epidemiologic studies on APIAs based on representative samples leaves us without adequate knowledge of the diversity in culture and health of this special population. The low cholesterol levels of the Japanese serve as useful references for the control of coronary heart disease in mainstream America, but has the lesson been learned and disseminated as widely with regards to the high risk of stroke among the Japanese? And have we focused sufficient attention on the control of trigylcerides among APIAs in order to reduce, possibly, their risk for strokes—a disease which strikes APIAs at a higher proportion than white Americans? These questions illustrate the importance of collecting baseline epidemiologic data on specific ethnic populations and the value of understanding why a piece of epidemiologic research is undertaken, who it benefits, and what uses are made of the findings. These are clearly politically charged issues, ones that would become even more so if left unattended. A striking contrast between the black American's and the APIA's perspectives on the legal and ethical issues in clinical studies is that while black-Americans have had a history of slavery and have been the object of abuses in medical research (the Tuskegee Syphilis Study being the most glaring of such violations), APIAs suffer from just the opposite—a lack of studies based on representative samples that would adequately reflect the cultural diversity of this special population and inform us of their most troubling health conditions. Consequently, the few studies that exist, which were based on the most economically successful group—the Japanese—and the most accessible one—because they primarily speak English—are used to overgeneralize "all" APIAs. Social class differences between the Japanese and white American populations are seldom rigorously controlled such that observed differences are quickly attributed to basic "racial" differences when in fact they may be socioeconomic in nature. In the absence of any good descriptive baseline data about Asian Americans and Pacific Islanders, and evidence of an inadequate record of training minorities to become principal investigators of large-scale studies, the USPHS effort to include a large sample of APIA populations in clinical studies is scientifically premature and viewed with considerable suspicion by the educated members of the APIA community. Every effort must be made to answer the fundamental question—research for what purpose and to whose benefit?—before embarking on any major clinical trials involving vulnerable populations. More minority investigators will have to be trained and become equal partners of research with mainstream investigators in order to ensure the representation of minority perspectives in research.
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