Haas, David M. MD, MS1,2; Renbarger, Jamie L. MD, MS1,2; Meslin, Eric M. PhD3; Drabiak, Katherine JD3; Flockhart, David MD, PhD2
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The explosion of genetics in medicine has created tremendous promise for better treatment but has also opened up many practical and ethical considerations. With the human genome sequenced, investigators are identifying genetic variations between individuals that can identify people at risk for disease. The field of pharmacogenetics promises that knowing an individual’s genotype can also allow for targeted interventions, maximizing efficacy while minimizing adverse effects of medications.1 Additionally, pharmacogenetics can allow for personalized drug therapy and improved allocation of healthcare resources.1,2
While obtaining DNA to improve patient care is the goal, biological samples first must be obtained for the research purposes to establish genetic associations with disease, a situation that may challenge traditional informed consent norms.3 Collecting biological specimens for research is supported by most surveyed populations.4,5 It has also been shown that people favor donation of specimens to biobanks designed for research in the future.6,7 While surveyed populations tend to reply favorably to supporting sample donation, their knowledge about the research to be done is usually lacking, despite consenting procedures.8 Furthermore, there is a known positive correlation between understanding of the research and a participant’s willingness to donate samples.9,10 As such, there is a need to educate both the population and healthcare providers regarding the field of pharmacogenetics.11,12
Pharmacogenetics may be of profound importance in obstetrics and women’s health, in which one must consider effects of medications on both the mother and fetus. Minimizing exposure of the fetus to drugs is an important consideration in treating the mother. While it has been demonstrated that pregnant women support unrelated umbilical cord blood donation,9 the majority report poor knowledge about the actual practices and uses of the samples.13 A recent survey by the National Institute of Child Health and Development’s (NICHD) Maternal–Fetal Medicine Units network found that, while 72% of women would give unrestricted permission to use their banked specimens, 20% noted that they wanted their specimens destroyed, not to be used in any other research.14 This is the only study to our knowledge evaluating pregnant women’s opinions about using their banked specimens for genotyping.
The objective of this project was to estimate if women would be willing to donate specimens for DNA analysis if it required phlebotomy compared with collection of saliva. DNA is now reliably obtained from both blood and saliva, but collecting each carries different burdens and risks for patients which might influence their decision to donate specimens. While blood samples may be used for more than DNA analysis, saliva is easier to obtain. Additionally, this survey sought to confirm the findings of the NICHD study regarding whether women would be more likely to give permission for DNA analysis of prior specimens or would want their specimens destroyed.
METHODS AND METHODS
This project was approved as an exempt study by the Indiana University/Purdue University Indianapolis Institutional Review Board. We performed a cross-sectional, anonymous survey of women attending the obstetrics and gynecology clinics at Wishard Memorial and University Hospitals in Indianapolis, IN, both urban hospitals. Wishard Memorial Hospital is an urban county hospital serving the poor and uninsured population of Marion County, IN. Fifty-five percent of the patients receive uninsured charity care, 22% Medicaid, 13% Medicare, 7% private insurance, and 3% self-pay. University Hospital is an urban referral center. The insurance payors for women attending the obstetrics and gynecology clinic at University Hospital is 25% Medicaid, 47% managed care, 19% commercial, 6% Medicare, and 3% self-pay. Women who presented to the obstetrics and gynecology clinic for either an obstetric or gynecologic appointment were asked at the front desk when they checked in if they were willing to complete a short survey. A survey was given to each woman who agreed to participate with the instructions to return the survey to the front desk collection box upon completion. The women were also given the option to complete the survey in the privacy of their examination room before being seen by a provider. Women who are unable to understand these instructions, did not speak English or Spanish, or had completed the survey at a previous visit, were not given a survey. Completed surveys were removed from the collection box weekly, thus making it nearly impossible to link a particular survey with a person’s appointment day or time. The survey was administered over a 5-week period from June 2007 to July 2007.
With the assistance of The Survey Research Center at Indiana University-Purdue University-Indianapolis, the survey instrument (see the Appendix online at www.greenjournal.org/cgi/content/full/112/5/1023/DC1) was developed by the research team to incorporate the findings and some of the questions of prior studies.14 This survey was designed to ascertain if women attending an obstetrics and gynecology clinic had an understanding of genetic tests, if they would agree to have their DNA collected, and if so by what means. The survey also asked if they would allow researchers to use specimens already in the laboratory for research purposes. Both English and Spanish surveys were available. The survey was translated and reverse translated by a certified translator and hospital interpreter with any differences in the translation resolved through discussion. The Spanish translation of the survey is available from the authors upon request. The survey was pretested with several patients in clinic to ensure understandability.
Data were collected and analyzed by SPSS 15.0 (Chicago, IL). Descriptive statistics are reported. The χ2 test was used to compare discreet variables, and t tests or analysis of variance was used to compare continuous variables. McNemar’s χ2 test was used to test the association of the proportions of women replying they would donate by needlestick compared with those replying they would donate by saliva. A logistic regression analysis was performed to assess the factors most closely associated with a person’s willingness to donate specimens for genetic studies. The model was constructed to contain clinical variables that have been found previously to be associated with willingness to donate or that were thought to be clinically relevant variables to estimate a patient’s willingness to donate. The model included ethnicity, age, knowledge (good grasp of knowledge or better compared with less than that), education level, and how engaged one was in her religious faith (attending services at least once per month compared with less than once per month or never). For the regression analysis, women were categorized as likely to donate specimens if they answered “likely” or “very likely” when asked if they would allow their DNA to be collected. Women were categorized as giving permission for future use if they answered that at the time of collection of specimens, they would give permission for the use of their DNA for future research in any condition or for future research regarding the condition for which they originally gave the sample. The survey was designed to be available for 5 weeks. No a priori sample size calculation was performed.
A total of 359 surveys were distributed over the course of 5 weeks. Two hundred seventy-nine (77.7%) were returned. Most of the surveys (92.5%) came from the Wishard Hospital clinic. The mean age of respondents was 29.3±11.5 years. One hundred forty-seven women (53.5%) answered that they were pregnant. Seventy-six (31.7%) were Caucasian, non-Hispanic, 77 (32.1%) were African American, non-Hispanic, 70 (29.2%) were Hispanic, and 17 (7.1%) marked other ethnicity. Eleven women marked “prefer not to say.” This ethnic distribution is generally reflective of the overall clinic population. Of the 70 women who marked that they were Hispanic, only one marked “African-American/Black” as her ethnic group. The remainder mostly reported their ethnic group as “Other,” “Caucasian,” or left it blank. Thus, Hispanic race was incorporated into the ethnicity analyses, giving four ethnic groupings for all comparative analyses: African American, Caucasian non-Hispanic, Hispanic, and Other. Regarding education level of the respondents, 67 (26.7%) did not finish high school, 80 (31.9%) finished high school, 54 (21.5%) had attended some college, 32 (12.7%) had completed college, 12 (4.8%) had attended postgraduate training, and 6(2.4%) chose not to answer. Most women (n=139, 57.0%) considered themselves members of a religious faith, while 70 (28.7%) did not, and 35 (14.3%) chose not to answer. Of those who wrote a response for what faith they belonged to, the overwhelming majority of the women were of a Christian faith with 33% responding “Christian,” 27% “Catholic,” and 23% “Baptist.”
In general, the majority of women are not very knowledgeable about genes and DNA with 30 (10.8%) stating they had no knowledge, 65 (23.5%) “a little,” 70 (25.3%) “somewhat knowledgeable,” 59 (21.3%) “good grasp of knowledge,” 18 (6.5%) “more advanced knowledge,” and 35 (12.6%) stating they “fully understand” genes and DNA. Despite this, the majority of women felt that collecting genetic material was a worthy scientific pursuit (n=210, 77.2% said yes; n=13, 4.8% said no; n=49, 18% didn’t know). When asked how likely they would be to allow their DNA to be collected, 28 (10.6%) stated “very likely,” 69 (26.2%) “likely,” 53 (20.2%) “somewhat likely,” 61 (23.2%) “a little likely,” 39 (14.8%) unlikely, and 13 (4.9%) stated they would never allow their DNA to be collected. Thus, while more than three quarters said that it was a worthy endeavor, only a little more than one third were likely or very likely to donate specimens.
Table 1 displays the distribution of women replying whether they would allow their DNA to be collected by either blood (needlestick) or saliva. Overall, 68.3% of women said they would donate a specimen for DNA by needlestick, compared with 75.7% who said they would donate saliva (P=.003). A large number of women replied that they did not know if they would donate a sample by either method (n=54, 20.1% for blood; n=45, 16.8% for saliva). The mean ages of women were not different based on their response to whether they would donate by needlestick or saliva. Women who would donate by needlestick had a mean age in years of 30.4±12.5, compared with 25.5±7.0 for those who would not, and 28.7±10.2 for those who did not know (P=.10). Women who would donate by saliva had a mean age in years of 30.0±12.3 compared with 27.4±9.9 for those who would not and 27.1±8.9 for those who did not know (P=.26). There was a statistically significant difference in willingness to donate blood among ethnic groups with Caucasians more willing to donate blood than other ethnic groups. We did not detect a difference in willingness to donate saliva among ethnic groups. While a higher percentage of women in each ethnic group would be willing to donate saliva versus blood, the only group where this difference in opinion approached statistical significance was for Hispanics (P=.06).
Regarding the use of existing specimens, 81 women (31.3%) would give permission for any previously obtained samples to be used in the future for genetic tests, 158 (61.0%) would want to be asked before any further testing was done, 12 (4.0%) were certain they would want no further tests done, and 8 (3.1%) would want any existing specimens destroyed. Regarding consent for future use of specimens that were being given at that time, 97 (38.2%) would give permission for the use of their DNA for future research on any health or medical condition, 41 (16.1%) would give permission for use in future research regarding the condition they originally gave the sample for, 78 (30.7%) would want to be asked first before using their samples for anything else, and 38 (15.0%) would not want any further tests done on their DNA samples. We did not detect statistically significant differences in the responses to either of these questions among different ethnic groups, level of education, level of attendance at religious services, or level of understanding about genes and DNA or whether the woman was pregnant.
Because we wished to estimate which factors were most associated with women being likely to donate specimens for genetic studies and what factors were associated with giving permission for future use of specimens at the time of donation, we built a logistic regression model based on variables that could influence a person’s decisions regarding this type of research. Table 2 represents the results of the logistic regression. At least having a good grasp of the knowledge in the area was consistently associated with both likelihood to donate specimens and giving permission for future use of the specimens in genetic studies. Having completed college or further education was also associated with a willingness to donate specimens, whereas women who were more religiously engaged were less likely to donate than those who did not attend religious services as often.
We found that, in our urban, ethnically diverse population of women, the majority would be willing to donate a small amount of blood or saliva to obtain DNA. We also found that only a small number of women (7.1%) would not want existing specimens used again, or would go so far as to want them destroyed. This was in contrast to the findings of the NICHD study that found that more than 28% of Hispanics and almost 20% of African Americans wanted their specimens destroyed.14 We found no difference in the responses to this question based on ethnicity in either the univariable or multivariable analysis. More of our respondents wanted to be asked to use their specimens, as opposed to giving unrestricted permission, the converse of the NICHD study findings.14 One reason for this difference may be that we surveyed an unselected population, whereas the NICHD study queried women who had already once consented to participate in research. A study of cancer patients who had already donated specimens to a tissue bank also found that those patients would allow for future use of their specimens without being recontacted.7 These groups were likely a priori favorably disposed to research as opposed to our unselected population.
Most women reported lower knowledge levels regarding DNA and genes. This is consistent with other studies that demonstrate low knowledge levels in both the public and healthcare workers regarding these issues.8,11,13,15 One of the distinct challenges facing the translation of pharmacogenetics into clinical practice is overcoming the knowledge gap among researchers, clinicians, and patients.15 This is particularly important given our findings that women who were more knowledgeable were more than twice as likely to donate specimens and give permission for use of specimens in the future. Ensuring women understand the purpose of the donation, through education during the informed consent process, is the only ethical way to perform these studies.
In general, the majority of people find the scientific inquiry into genetics and biobanks worthwhile.4–6 One recent study even confirmed that patients would be willing to pay for genetic screening tests for colorectal cancer.16 Our findings confirm these general results. Perhaps reflecting the lack of knowledge described above, however, these positive feelings did not translate into a majority of women expressing their willingness to donate samples for these purposes. This is similar to the disconnect between favorable attitudes toward organ donation and those who actually sign organ donor cards and other advance directives for organ donation.17,18 The vague nature of the survey question may have contributed to the gap between feeling the research is worthwhile and actually being willing to donate. A patient’s unwillingness to participate may come from worries about the use of the specimens, violation of privacy, the potential for future discrimination, and the fear surrounding unfavorable results.13,19 Future inquiry into attitudes toward specimen donation should carefully elucidate reasons for a patient’s unwillingness to participate so that researchers and clinicians will be better able to adjust education programs and strategies to partner with the public in this research endeavor.20
We noted that more women would be willing to donate DNA specimens by saliva than by needlestick. Saliva has been repeatedly demonstrated to be a reliable source for DNA.21,22 Blood is often collected as part of routine clinical care and is more versatile in its potential uses for biobanks. Salivary DNA testing is noninvasive for patients. Rapid access to salivary DNA results may promote point-of-care genetic testing that would be more acceptable to the public than having to undergo a needlestick.23 It is also encouraging that, while there is a difference of willingness to donate blood for DNA among different ethnic groups, there was no significant difference in the willingness to donate saliva. This finding is encouraging, as minorities need to be represented in genetic association studies. It was also encouraging that the majority of pregnant women would also donate specimens by blood or saliva.
Interestingly, women who were more engaged in their religious practices were less likely to be willing to donate specimens. There was no difference, however, in their willingness to give permission for future use of those specimens. We are unaware of other studies that focus exclusively on patient attitudes toward genotyping that report religion as a significant cofactor, although some research has been on patient attitudes toward donation of tissues for research that suggests a positive correlation between donation and religiosity.24 It is reasonable that a person’s religious background may contribute to their willingness to participate in genetic studies. Perhaps a self-assessment of a person’s degree of religiousness would be a better measure of religious engagement than frequency of service attendance.
Our study had the limitations typical of most self-reporting patient survey. Our tool was not validated but utilized questions from other published surveys and was developed in conjunction with the Indiana University-Purdue University-Indianapolis Survey Research Center, which has a great deal of experience conducting patient-level surveys. It was given to a sample of patients for understandability of the questions and face validity. We allowed women to take the survey in a private setting and made it anonymous to strive to obtain honest answers. The survey was also translated into Spanish to incorporate the Spanish-speaking population into the analysis.
A potential reason for a lower willingness to have specimens collected may be the vague nature of the question. We attempted to make the questions flow logically from one to another. Specifying the intended use may have changed the willingness to donate. This will be corrected in future surveys. Another limitation is the difference between agreeing to donate samples in principle and actually donating in practice. After providing more information to the women during the informed consent process, the proportion of women agreeing to participate may be different from our results.
This survey of patient knowledge and attitudes toward genotyping found that more women would donate DNA with a specimen of saliva than with a blood sample. In addition, higher education levels and more knowledge were associated with likelihood to donate specimens and to give permission for future use of specimens in genetics research. This study demonstrates that, as pharmacogenetics and genotype association studies move into women’s health, the population is willing to participate in these studies if we are able to educate them properly regarding this area of scientific investigation.
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