Tissue and Data Ranking Journal o f Empirical Research on
S u rv e y o f A ttitu d e s o f Japanese W o m e n
Hum an Research Ethics 2014, Vol. 9(3) 2 9-3 8 © The A u th o r(s ) 2014
T o w a r d G e n e tic /G e n o m ic R e s e a rc h
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DSAGE H ir o m i M o r iy a 1, I t u r o In o u e 2, M a y u m i Ik e u c h i1, N a o a k i Is h ii1, a n d M a s a ru M o t o j i m a 1
A b s tra c t
Previous surveys have suggested th a t e ld e rly Japanese w o m e n have th e lo w e s t scien tific in te re s t and lite ra cy w ith in th e Japanese p o p u la tio n and am ong pop ulatio n s across W e s te rn co u n trie s. Because re c e n t tre m e n d o u s advances in genom e analysis are like ly to be in c o rp o ra te d in to standard b iom edical assessments th ro u g h o u t th e w o rld , w e co n d u cte d surveys to investigate th e a ttitu d e s to w a rd g e n etic/g e no m ic research o f Japanese w o m e n aged b etw e en 55 and 65 years. C u r re n t surveys indicate th a t o b ta in in g adequate in fo rm e d co n se n t fro m e ld e rly Japanese w o m e n is co m p lica te d. T h e lim ita tio n is especially re le va n t to p a rticip a n ts’ lite ra c y in genetics and gen om ic studies. Results o f th e surveys also indicate th a t even a fte r th e in fo rm e d co n se n t is o bta ine d, researchers m u st co n tin u e to supply updated stu dy in fo rm a tio n to th e study subjects, w h ich enables th e m to o bta in a dd itio n a l in fo rm a tio n on th e use o f th e ir samples and g e n etic/g e no m ic in fo rm a tio n . Failure to co n sid e r these o bliga tion s may lead to a loss o f th e p u b lic’s tr u s t and thus a ffe ct research progress on m edical genom ics.
K e y w o rd s
g e n e tic/g e n o m ic research, in fo rm e d consent, Japanese guidelines
In tr o d u c t io n
Surveys conducted by the National Institute of Science and Technology Policy (NISTEP) of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan in 2009 revealed that interest in issues of science and tech nology of Japanese people was lower than that of the United States and the United Kingdom (Second Policy-Oriented Research Group, NISTEP, MEXT, 2011). The surveys also showed that scientific literacy in Japan was the lowest among these countries. Furthermore, women scored lower in both scientific interest and literacy than men across all nationalities. In addition, decline of scientific literacy was observed in the elderly. These findings confirmed earlier surveys conducted in 14 countries, including Japan, the United States, the United Kingdom, and EU members (Second Policy-Oriented Research Group, NISTEP, MEXT, 2002). Together, these observations suggest that elderly Japanese women may be regarded as a group having the lowest scientific interest and literacy. Scientific interest and literacy of elderly Japanese women may play a critical role in shaping their perception of genetic testing and genetic/ genomic research, and in Japanese perception of genetic research generally. How might they wield such influence? In Japanese tradition, mothers are expected to play much greater roles in raising children than those of mothers in
most Western countries because many Japanese believe that it is a mother’s task and that fathers should work hard every day, although this trend may be weakening recently due to increasing number of working mothers. When a baby is born with a genetic disease, the mother bears a huge burden to take care of the child in Japan. In addition, Japanese mothers have been reported to experience extremely high negative pressure from older females as well as other family members if they have a child with a genetic disorder (Kawashima, 1992). Consequently, the perception of genet ics held by elderly Japanese women who have experienced child-raising may affect other family members’ decisions to participate in genetic/genomic research. In this article, we report the findings of surveys that assess basic attitudes of elderly Japanese women toward genetic/genomic research and identify potential obstacles in obtaining effective informed consent. There have been very few studies that specifically investigate attitudes toward genetic research.
'T o k a i U n iv e r s ity , Ise h a ra , Japan N a t i o n a l I n s t it u te o f G e n e tic s , M is h im a , Japan
C o r r e s p o n d in g A u t h o r : M a s a ru M o to jim a , D e p a r t m e n t o f C lin ic a l P h a rm a c o lo g y , S c h o o l o f M e d ic in e , T o k a i U n iv e r s ity , 143 S h im o k a s u y a , Is e h a ra , K a n a g a w a , Japan. E m ail: m - m o to ji@ is .ic c .u - to k a i.a c .jp
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Journal o f Empirical Research on Hum an Research Ethics 9(3)
By comparing the current surveys with previous reports, we can assess the effects of race, gender, and age on attitudes. Moreover, in February 2013, “The Ethical Guidelines for Analytical Research on the Human Genome/Genes” have been jointly renewed by three ministries of Japanese Government: the Ministry of Economy, Trade, and Industry; the MEXT; and the Ministry of Health, Labor, and Welfare of Japan. Many changes in the revised version loosen the requirements for the transfer of stored samples to other institutions. Thus, the revisions may facilitate accumulation of samples in huge repositories. The guidelines, which were originally established in 2002, were intended to serve as a “soft law.” In practice, Japanese researchers generally adhere to the guidelines, because otherwise, they may become the subject of criticism by the Japanese media, lose the trust of the general public, and lose support from the regulatory and funding agencies. Based on results of the current surveys, impacts of the current revisions on require ments for informed consent are discussed.
survey was approved by an institutional review board (IRB) in Tokai University School of Medicine (IRB File 10-206).
M e th o d
The first survey was conducted with 89 Japanese women, 55 to 65 years old (September 2010). The survey was intended to obtain information regarding basic knowledge of genetics and also to assess their primary attitudes toward genetic/genomic research of common diseases. Three months later, a second survey was conducted with the same participants ( n = 85). Before administration of the second survey, a 30-min seminar explaining genetic/genomic research of common diseases was provided by the genome medical research coordinator (H.M.) that simulated the informed consent process to enroll participants. The semi nar covered the following topics: significance of genetic research, genes genome DNA, genes and diseases, method ology of genetic research, interpretation of results of genetic research, and benefits and risks of study participation. The second survey was designed to evaluate alterations in the participants’ attitudes after the seminar, and therefore, con tained more detailed questionnaires. One year later (December 2011), a third survey was con ducted in 105 new participants. This survey was intended to confirm findings of the previous two surveys. Consequently, this third survey combined the questions contained in the prior two surveys, but omitted the complicated questions covered in the previous seminar, as the seminar had not been taken by the new participants. All survey participants were recruited from among sub jects who voluntarily participated in a clinical study titled “An Intervention Study on Excise and Nutrients to Establish a Health Index” conducted by the Life-Care Center, Tokai University School of Medicine. This clinical study aimed to assess the effects of exercise and diet supplements on the health status of healthy Japanese women. The current
R esu lts a n d D iscu ssio n Answers to Questions Regarding Basic Knowledge o f Genetics
In the first survey, 43% of the participants answered that they understood the meaning of the word, “gene” (Table 1, Ql). The rest of the participants had some knowledge about the meaning of the word. Similarly, 51% of the participants understood the meaning of the word, “DNA” (Table 1, Q2), and the rest of the participants had some knowledge about the word. In contrast, only 8% of the participants under stood, and 30% had not heard of the word, “genome” (Table 1, Q3), and therefore, had difficulty understanding the dif ference between gene and genome (Table 1, Q4). In the third survey, 47% understood the meaning of “gene,” 39% understood the meaning of “DNA,” but only 3% understood the meaning of “genome” (Table 3, Q l, Q2, and Q3), thereby, confirming the first-year findings. Whole genome sequencing, also frequently referred to as “personal genome sequencing,” is rapidly being incorporated into routine assessments in clinical research and may bring some new bioethical concerns (Hudson, 2011; Motojima & Ichikawa, 2009; Motojima, Inoue, Yonemoto, & Ichikawa, 2011; van El et al., 2013). In this regard, the meaning of “genome” was too complicated to understand by the survey partici pants and, therefore, may be too complex for subjects in particular studies that involve genetic/genome analysis. Such limitations may become a more urgent concern in an era of whole genome sequencing when obtaining effective informed consent. Some researchers have given up informed consent with adequate understanding (Angrist, 2009). In the second survey, although 54% understood the sem inar well (Table 2, Q13), some participants commented that confidence of their understanding became weaker after the seminar. Therefore, researchers should keep in mind that repeated explanations about genetic/genomic research dur ing the informed consent process are needed until study subjects’ understanding of the genetic/genomic research is assured. Ideally, depending on subjects’ literacy in genetics and genomics, researchers should try not to obtain consent at the first visit and wait until the following visit so as to give them sufficient time to consider the study. Effects o f Inform ation Seminar on Attitudes Toward Genetic!Genomic Research o f Common Diseases
In the first survey, 35% of the participants showed a strongly positive attitude toward participating in genetic research of common diseases (selected “Definitely yes” in Table 1, Q9)
Moriya et al.
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T a b le I . First Q u e stio n n a ire (Septem ber 2010).
%(n) Q 1. D o you kn o w th e w o rd “ gene” ? Yes 1 do. 1 k n o w th e meaning.
43 (38)
Yes, 1 do. 1 have heard o f it.
57 (51)
No
0 (0 )
Q 2. D o you kn o w th e w o rd “ D N A ” ? Yes 1 do. 1 k n o w th e meaning.
51 (45)
Yes, 1 do. 1 have heard o f it.
48 (43)
No
0 (0 )
Q 3. D o you kn o w th e w o rd “ genom e” ? Yes 1 do. 1 k n o w the meaning.
8 (7 )
Yes, 1 do. 1 have heard o f it.
62 (55)
No
30 (27)
Q 4. Can you distinguish “ gene” fro m “ genom e' 7 Yes 1 can. 1 k n o w th e difference.
6 (5 )
Perhaps
30 (27)
No
64 (57)
Q 5. Have you ever participated in genetic research? Yes No
1 (1) 98 (87)
Q 6. T h e re are a p p roxim ately 22,000 genes in human. G enetic research reveals genes th a t de te rm in e susceptibility to many diseases and tra its such as hypertension, diabetes, and height. D o you w a n t to learn m o re about genes? Strongly positive
37 (33)
Som ew hat positive
53 (47)
N o t sure
7 (6 )
Som ew hat negative
0 (0 )
No
0 (0 )
Q 7. D o you w a n t to kn o w y o u r genotype? Strongly positive
54 (48)
Som ew hat positive
40 (36)
N o t sure
3 (3 )
Som ew hat negative
0 (0 )
N ever 0 (0 ) Q 8. D o you th in k y o u r genetic in fo rm a tio n reflects y o u r fam ily’s a n d /o r relative's inform ation? Yes
94 (84)
No
0 (0 )
1 d o n ’t know .
3(3)
Q 9. W ill you participate in genetic research th a t seeks susceptible genes o f lifestyle diseases such as diabetes, obesity, and hypertension? D e fin ite ly yes
35 (31)
Maybe yes
34 (30)
1 d o n ’t know .
17 (1 5 )
Maybe no
6 (5 )
N ever
0 (0 )
Depends on th e type o f study.
7 (6 )
Note. Participant number: 89.
and 34% were more tentative about participation (selected “Maybe yes”). Overall, almost 70% of the participants showed positive attitudes. Similar results were obtained in the third survey showing that 35% chose “Definitely yes” and 40% chose “Maybe yes” (Table 3, Q9). Positive atti tudes toward participating in genetic research have also been reported from Sweden, Iceland, the United Kingdom, Ireland, the United States, Scotland, Saudi Arabia, and Jordan (Ahram, Othman, & Shahrouri, 2013; Al-Jumah et al., 2011; Johnsson et al., 2010; Treweek, Doney, & Leiman, 2009). After the seminar, the number of strongly positive participants was reduced to 20% (Table 2, Q2) and the number of somewhat negative (from 6% to 12%) and strongly negative participants (from 0% to 1%) doubled indicating that increased knowledge about genetic/genomic research affects decision making. The increased negativity is apparently due to their having realized how knowing their genotype can affect their life and hence, having become anxious about participating in genomic research. In the first survey, most participants showed positive attitudes toward knowing their own genotype (Strongly positive: 54%, Somewhat positive: 40%, Table 1, Q6). This trend was confirmed by the third survey (Strongly positive: 56%, Somewhat positive: 40%, Table 3, Q6). Even after the seminar, almost half of the participants remained interested in obtaining their own test results of genetic/genomic research despite an explanation that results of genetic stud ies mostly provide uncertain results (Everything including uncertain results: 52%, Table 2, Q10). However, the number of participants who showed negative attitudes toward know ing their genotype increased after the seminar, from 0% to 7% (Somewhat negative: 7%, Table 2, Q10). These overall results indicate that understanding of genetic/genome research in elderly Japanese women is rather limited and that it needs to be reinforced with repeated explanations. “The Ethical Guidelines for Analytical Research on the Human Genome/Genes” recommend dis closing results of genetic tests or genome analysis to study subjects. However, when the preliminary results are likely to cause confusion and/or anxiety, researchers can choose not to disclose the results under the new guidelines. Controversy regarding whether and how to disclose research results of genetic analysis have a long history in worldwide ethical debates (Hudson, 2011). When disclosing test results to a subject, a research team needs to consider whether the subject has adequate literacy in genetics/genomics to under stand the test results, and whether disclosure of test results benefits the subject. The research team should provide an opportunity for participants to learn more about genetics/ genomics if the team decides to disclose test results to sub jects with low genetic/genomic literacy. The researchers
32 T a b le 2.
Journal of Empirical Research on Human Research Ethics 9(3) Second Questionnaire After a Seminar (December 2010). % (n)
Q 1. Do you want to learn more about gene, genome, and DNA? 39 (33) Strongly positive 46 (39) Somewhat positive II (9) Not sure 4(3) Somewhat negative No 1 (1) Q2. Will you participate in genetic research if you are asked to join the research? 20 (17) Definitely yes 48 (41) Maybe yes 12 (10) 1don't know. 12 (10) Maybe no Never 1 (1) 5(4) Depends on the type of study. Q3. For participants who answered “ (1) Definitely yes” or “ (2) Maybe yes" in Question 2, please choose the most appropriate reason to participate in the study. 25 (21) The research may improve medicine. 4(3) 1want to cure disease(s) that 1suffer from. 35 (29) 1want to know my susceptibility to diseases. 7(6) 1want to contribute to the progress of science. 1 don’t have any reason to refuse. 1 (1) 0(0) Others Q4. For participants who answered “ (5) Never” or “ (4) Maybe no” in Question 2, please chose the most appropriate reason not to participate in the study. 4(3) 1don’t want to know my susceptibility to diseases. There is a risk of leaking my personal information. 1 (1) 2(2) My susceptibility to diseases may uncover my families’ disease. 1can’t imagine what kind of harm arising from the study. 1 (1) 1can’t understand gene and genome. 3(3) 0(0) Others Q5. For participants who answered “ (6) Depends on the type of study” in Question 2, what kind of study will you participate in? Please specify. Preventive medicine. Future cure of intractable diseases, cancer, etc. Results of the study increase the possibility of prevention or cure of the disease. Studies intend to prevent or cure the disease. Also depend on the type of disease. Q6. Do you think that the explanation provided by study personnel, that is, researcher or research coordinator, is necessary to make your decision to participate in genetic or genome research? 75 (64) Need detailed explanation 24 (20) Need general explanation 0(0) Either will do. 0(0) No Q7. What is the most important factor to make a decision to participate in a genetic study? 39 (33) The research purpose 19(16) Social significance of the study 13(11) Interest in the study 4(3) Reliability of the study personnel 0(0) Personality of the study personnel 16(14) Your own benefit (cure your disease, etc.) 5(4) Opinion of family members 2(2) Others (continued)
Moriya et at.
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T a b le 2. (continued)
% (n) Q 8. Degree o f im p orta n ce o f fo llo w in g issues in explanations o f genetic study (5 -p o in t scale): I = unimportant. 2 = slightly important, 3 important, 4 = very important, 5 = critical 5
4
3
Basic explanations a b o ut genes, genom e, and research.
48 (41)
25 (21)
1 8 (15)
1 (1)
1 (1)
Explanations on the disease o f th e study.
58 (49)
30 (25)
9 (8 )
1 (1) 0 1 (1) 0
2
1
Explanations about the relation betw een the disease and the gene.
58 (49)
31 (26)
7 (6 )
1 (1) 2 (2 )
Explanations a b o ut study m ethods.
51 (43)
25 (21)
1 9 (16)
2 (2 )
Explanations on th e handling o f personal info rm a tio n .
75 (64)
I I (9)
I I (9)
Explanations o f th e handling o f genetic in fo rm a tio n , medical records, blo o d samples.
72 (61)
1 8 (15)
8 (7 )
1 (1) 0
D isclosure o f study results.
58 (49)
22 (19)
I I (9)
5 (4 )
0
Explanations on benefits o f the study p articipation.
50 (42)
25 (21)
21 (18)
0
Explanations on risks o f th e study participation.
59 (50)
2 2 (1 9 )
1 5 (13)
1 (1) 0
Freedom to w ith d ra w a l fro m th e study.
58 (49)
25 (21)
I I (9)
4 (3 )
0
0
0
Q 9. H o w long do you w a n t to hear about the genetic study w hen you are asked to participate i Less than 5 min 5-10 min
0( 0) 1 4 (12)
10-30 min
1 4 (12)
30-60 min
60 (41)
M ore than 60 min
2 2 (1 9 )
Q 10. If you participate in a genetic study, do you w a n t to kn o w yo u r genotype, although the link betw een genotype and disease may be unclear? Everything including uncertain results
52 (44)
O n ly validated results
34 (29)
E ither w ill do
6 (5 )
Som ew hat negative
7 (6 )
N e ve r
0 ( 0)
Q I I . If a m uta tio n th a t causes a serious disease is found by chance, do you w a n t to be inform ed? Yes
65 (55)
Yes, b u t only in case th e re is a therapy o r prevention
29 (25)
No
I (I)
N o , b u t te ll the resu lt to m y fam ily o r hom e d o c to r
2 (2)
O th e rs (I) Q 1 2. If y o u r sample is used fo r a new study th a t was n o t explained d u ring th e initial in form ed consent, do you wish to participate in th e study? Yes, 1 do.
18 (1 5 )
Yes, b u t 1 re s tric t th e use o f my sample to th e study.
1 0 (9 )
Yes, b u t 1 need to be inform ed as to w h a t is the in te n t o f the study.
40 (34)
Yes, b u t com m unicate w ith me a b o ut w h a t study it is to be used by In te rn e t o r a p o ste r in the hospital.
1 (1)
Yes, b u t my sample should be com pletely anonymous.
15 (1 3 )
N o , 1 d o n ’t.
13 (1 1 )
O th e r
2 (2 )
Q I3 . D id you understand to d ay’s seminar well? Yes, 1 u n d ersto o d it com pletely.
16 (1 4 )
Yes, 1 u n d ersto o d it well.
38 (32)
H alf o f it.
3 6 (3 1 )
N o t so well.
6 (5 )
N o t a t all.
0 (0 )
Note. Participant number: 85.
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Journal o f Empirical Research on Hum an Research Ethics 9(3)
Table 3.
Third Questionnaire of New Volunteers (December 2011, Second Year). % (n)
Q 1. D o you know the w o rd “ gene” ? Yes 1do. 1 know the meaning.
47 (49)
Yes, 1 do. 1have heard o f it.
53 (56)
No
0 (0 )
Q2. Do you know the w ord “ D N A ” ? Yes 1do. 1 know the meaning.
39 (41)
Yes, 1 do. 1have heard o f it.
58 (61)
No
1 (1)
Q3. D o you know the w ord “ genome” ? Yes 1do. 1 know the meaning.
3(3)
Yes, 1 do. 1have heard o f it.
69 (72)
No
29 (30)
Q4. Can you distinguish “ gene” from “ genome” ? Yes 1can. 1 know the difference. Perhaps
1 (1) 28 (29)
No
70 (74)
Q5. Have you ever participated in genetic research? Yes Never
1 (1) 98 (103)
Q6. There are approximately 22,000 genes in human. Genetic research reveals genes that determine susceptibility to many diseases. Do you want to learn m ore about genes? Strongly positive
31 (33)
Somewhat positive
58 (61)
N o t sure
8 (8 )
Somewhat negative
2 (2 )
Never
0 (0 )
Q7. D o you want to know your genotype? Strongly positive
56 (59)
Somewhat positive N o t sure
40 (42)
Somewhat negative
1 (1) 0 (0 )
Never
2 (2 )
Q8. Do you think your genetic information reflects your family’s information? Yes
94 (99)
No
2 (2 )
1don’t know.
1 (1) Q9. W ill you participate in genetic research that seeks susceptible genes o f lifestyle diseases such as diabetes, obesity, and hypertension? 35 (37) Definitely yes Maybe yes
40 (42)
1do n't know.
19 (20) 4 (4 )
Maybe no Never
0 (0 )
Depends on the type o f study.
2 (2 ) QIO. For participants w ho answered “ (1) Definitely yes” o r “ (2) Maybe yes” in Question No. 9, please choose the most appropriate reason to participate in the study. 21 (22) The research may improve medicine. 1want to cure disease(s) that 1 suffer from. 1want to know my susceptibility to diseases. 1want to contribute to the progress of science. 1don’t have any reason to refuse. Others
5 (5 ) 47 (49) 2 (2 ) 2 (2 ) 0 (0 ) (continued)
Moriya et al.
35
T a b le 3. (continued)
__________________________________ %(n) _________ Q I I . For participants w ho answered “ (5) N ever” o r “ (4) Maybe no” in Question 9, please choose the most appropriate reason not to participate in the study. I don’t want to know my susceptibility to diseases.
2 (2)
There is a risk o f leaking my personal information.
0 (0)
My susceptibility to diseases may uncover my families’ disease.
0 (0)
I can’t imagine what kind of harm w ill arise from the study.
0 (0)
I can’t understand gene and genome. O thers
0 (0) |
Q 12. For participants w ho answered “ (6) Depends on the type o f study" in Question 9, what kind o f study w ill you participate in? Does not cause mental stress N o answer Q 1 3. D o you want to learn more about gene, genome, and DNA? Strongly positive
27 (28)
Somewhat positive
60 (62)
N o t sure
8 (8)
Somewhat negative
2 (2)
No
0 (0)
Q I4 . D o you think that the explanation by the study personnel is necessary to make your decision to participate in genetic o r genome research? Need detailed explanation Need general explanation
84 (88)
10 ( 10) 2 (2) 0 (0)
Either w ill do. No Q 1 5. W h a t is the most im portant factor to make a decision to participate in a genetic study? The research purpose
55 (58)
Social significance o f the study
12(13)
Interest in the study
15(16)
Reliability o f the study personnel
3 (3 )
Personality of the study personnel
0 (0 )
Y our own benefit (cure your disease, etc.) Opinion of family members
6 ( 6)
O thers
0 (0 )
3(3)
Q 1 6. H ow long do you want to spend to hear about the genetic study when you are asked to participate in? Less than 5 min 5-10 min
0 ( 0) 4 (4 )
10-30 min
13(14)
30-60 min
49 (51)
More than 60 min
29 (30)
Q 1 7. If a mutation that causes a serious disease is found by chance, do you want to be informed? Yes
90 (94)
Yes, but only in case there is a therapy o r prevention. No
5 (5 )
No, but tell the result to my family o r home doctor. Others
I (I) 0 (0 )
I (I)
Note. Participant number: 105.
may consult with the IRB for additional guidance; many Japanese institutions have IRB members specializing in reviewing genetic/genomic research. In the second (post-seminar) survey, 65% of the partici pants wished to be informed about incidental findings that
cause serious diseases regardless of an available cure or pre vention, whereas 29% wanted to be informed about inciden tal findings only if a cure or prevention is available (Table 2, Q11). In the third survey, 90% wished to be informed of incidental findings, and only 5% wished to be informed
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Journal o f Empirical Research on H um an Research Ethics 9(3)
when prevention or cure is available (Table 3, Q17). Therefore, the seminar may have increased participants’ understanding of a “right not to know” and the limitations of genetic/genomic findings. However, the majority of the survey participants still wished to know incidental findings regardless of prevention or cure. Researchers or professional geneticists may overestimate public understanding of genetics and genomics (Condit, 2010). Disclosing incidental findings to study subjects with out adequate explanation and genetic counseling may cause unnecessary anxiety especially when their literacy in genet ics and genomics is low. It is therefore recommended that during informed consent, researchers provide sufficient explanations about types of incidental findings that may emerge, including the chance of prevention and/or the avail ability of therapy of the particular disease especially when subjects’ literacy in genetics and genomics is low.
study is disclosed to the public by an Internet website or a poster in the responsible hospital. According to our second survey, if the survey participants were asked to donate their DNA samples for a study that was not specified in the con sent form, only 1% of them would agree to the use of their samples without re-consent for a new study even when information on the study is disclosed by Internet or posters in responsible hospitals (Table 2, Q12). The Japanese ethical guidelines have shifted toward shared use of DNA samples, genetic/genomic information, and medical records to promote deposits from institutions to huge repositories. In the previous guidelines, when a researcher transfers research participants’ samples and ano nymized medical records to other institutions, the samples and medical records need to be completely de-identified by removing all personal identifiers. The revised guidelines permit retention of a correspondence table that enables link age of personal information and a code replacing personal identifiers in a sample and clinical information. It also per mits obtaining so-called “broad consent” for future studies. Thus, repositories that collect DNA/tissue samples and medical records of research participants can update partici pants’ medical records in ongoing and future studies. It is probable that in the future, DNA samples, genetic/genomic information, and medical records of study subjects will be used in research that the subject never imagined. The cur rent surveys demonstrate that regarding the use of samples for a new study, 10% preferred restricting the use to the study indicated, 40% requested researchers to inform them directly about the purpose of the new study, 15% refused to take part in the study, and 13% accepted only if the samples are fully de-identified to disconnect them from their per sonal information (Table 2, Q12). Thus, the majority of the survey participants reveal a preference to be directly informed as to what studies their samples and information will be used. This attitude of the survey participants may not be limited to elderly Japanese women. In a survey con ducted in New York, more than 60% of the participants felt uncomfortable with the use of their samples in a new study and worried about the new study (Kerath et al., 2013). In a survey conducted in Finland, one third would require re consent for every new study and 44% would like to limit the use of their samples (Tupasela et al., 2010).
Responses to Questions Regarding Informed Consent In the second survey after the seminar, 75% of the partici pants requested detailed explanation of the genetic research when they were asked to participate in a research project (Table 2, Q6). Although the adequacy of explanation is often a qualitative matter, it is necessary to devote sufficient time to ensure adequate understanding of the scientific con cepts. Because 60% of the participants chose 30 to 60 min as appropriate time to spend for the explanation (Table 2, Q9), this implies a 30- to 60-min informed consent process. In the third survey, 30 to 60 min was also the most preferred duration of time for the explanation (49% chosen, Table 3, Q16). Therefore, it appears that 30 to 60 min is recognized as an appropriate time length to understand issues of the informed consent by elderly Japanese women. To assess the concerns about participating in a genetic study, we asked the survey participants to rank the impor tance of issues explained (Table 2, Q8). Handling personal information (75% chose “Critical”) as well as genetic infor mation, medical records, and samples (72%) was identified as the most important issue, indicating that the major con cern of the survey participants is how the confidentiality of their personal information and samples is protected and secured. Similarly, in a survey conducted in New York, a major reason for refusing to participate in a huge repository of DNA and health records was personal privacy (Kerath et al., 2013). Of note, a recent survey comparing 10 differ ent countries showed that the Japanese population, includ ing both men and women, was most concerned about protecting personal information (Yamamoto et al., 2011). In the Japanese ethical guidelines, researchers are allowed to use genome DNA samples without obtaining re consent when meeting all of the following conditions: (a) It is impossible to obtain re-consent from the subjects, (b) the IRB approves the use, and (c) the information on a new
Conclusion The surveys indicated limited understanding of genetic con cepts in elderly Japanese women. However, their attitudes toward genetic research were similar to previous reports from other countries. Best Practices Researchers may need to provide extensive, and even redun dant, explanations about genetic/genomic research to obtain
Moriya et al.
adequate informed consent. They should provide genetic counseling if results or incidental findings are to be returned to study subjects. And they should provide updated informa tion when donated samples are to be re-used in new studies. Research Agenda
Further research is needed to assess how their knowledge of genetics/genomics, age, and gender affects their attitudes toward genetic/genomic research. We also need to clarify what knowledge of genetics/genomics are required for adequate decision making to participate in genetic/genomic research. E ducational Im plication
IRB members and researchers need to be taught about basic genetics/genomics and research ethics. A c k n o w le d g m e n t
The authors thank Dr. Valentina Kon, Vanderbilt University, for advice and comments on the article. D e c l a r a t i o n o f C o n f l ic t i n g In t e r e s t s
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. F u n d in g
The author(s) received no financial support for the research, authorship, and/or publication of this article.
R e fe re n c e s
Ahram, M., Othman, A., & Shahrouri, M. (2013). Public support and consent preference for biomedical research and biobank ing in Jordan. European Journal o f Human Genetics, 21, 567570. doi: 10.1038/ejhg.2012.213 Al-Jumah, M., Abolfotouh, M. A., Alabdulkareem, 1. B., Balkhy, H. H., Al-Jeraisy, M. I., Al-Swaid, A. F., . . .Al-Knawy, B. (2011). Public attitude towards biomedical research at outpa tient clinics of King Abdulaziz Medical City, Riyadh, Saudi Arabia. East Mediterranean Health Journal, 17, 536-545. Angrist, M. (2009). Eyes wide open: The personal genome project, citizen science, and veracity in informed consent. Personalized medicine, 6, 691-699. doi: 10.2217/pme.09.48 Condit, C. M. (2010). Public understandings of genetics and health. Clinical Genetics, 77, 1-9. doi: 10.111 l/j. 13990004.2009.01316.x Hudson, K. L. (2011). Genomics, health care, and society. New England Journal o f Medicine, 365, 1033-1041. doi: 10.1056/ NEJMral010517 Johnsson, L., Helgesson, G., Rafnar, T., Halldorsdottir, I., Chia, K. S., Eriksson, S., & Hansson, M. G. (2010). Hypothetical and factual willingness to participate in biobank research. European Journal o f Human Genetics, 18, 1261-1264. doi: 10.1038/ejhg.2010.106
37 Kawashima, H. (1992). Different client's response at genetic clinics in Japan and the USA, and its ethical background. In N. Fujiki & D. R. J. Macer (Eds.), Human Genome Research and Society: Proceedings of the Second International Bioethics Seminar in Fukui, Eubios Ethics Institute (pp. 145146). Retrieved from http://www.eubios.info/HGR.htm Kerath, S. M., Klein, G., Kern, M., Shapira, I., Witthuhn, J., Norohna, N., . . .Taioli, E. (2013). Beliefs and attitudes towards participating in genetic research— A population based cross-sectional study. BMC Public Health, 13, Article 114. doi:10.1186/1471-2458-13-114 Motojima, M., & Ichikawa, I. (2009). The impact of recent revisions in the Japanese Ethical Guidelines for Clinical Research. Asian Bioethics Review, 1, 329-341. doi: 10.1353/ asb.2009.0003 Motojima, M., Inoue, I., Yonemoto, S., & Ichikawa, I. (2011). Progress in human genome research prompts a paradigm shift in research ethics. Rinsho Hyoka (Clinical Evaluation), 38, 855-867. Second Policy-Oriented Research Group, National Institute of Science and Technology Policy, Ministry of Education, Culture, Sports, Science and Technology. (2002). The 2001 survey fo r public attitudes towards and understanding o f science & technology in Japan. Retrieved from http://www .nistep.go.jp/achiev/sum/eng/rep072e/rep72se.pdf Second Policy-Oriented Research Group, National Institute of Science and Technology Policy, Ministry of Education, Culture, Sports, Science and Technology. (2011). International comparison o f the public attitudes towards and understanding o f science and technology: Comparative study o f internet survey in Japan, the United States o f America, and the United Kingdom. Retrieved from http://www.nistep.go.jp/ achiev/abs/eng/mat 196e/pdf/mat 196ae.pdf Treweek, S., Doney, A., & Leiman, D. (2009). Public attitudes to the storage of blood left over from routine general prac tice tests and its use in research. Journal o f Health Service Research Policy, 14, 13-19. doi: 10.1258/jhsrp.2008.008016 Tupasela, A., Sihvo, S., Snell, K., Jallinoja, P., Aro, A. R., & Hemminki, E. (2010). Attitudes towards biomedical use of tissue sample collections, consent, and biobanks among Finns. Scandinavian Journal o f Public Health, 38, 46-52. doi: 10.1177/1403494809353824 van El, C. G., Cornel, M. C., Borry, P., Hastings, R. J., Fellmann, F., & Hodgson, S. V., . . . ESHG Public and Professional Policy Committee. (2013). Whole-genome sequencing in health care: Recommendations of the European Society of Human Genetics. European Journal o f Human Genetics, 21, 580-584. doi: 10.1038/ejhg.2013.46 Yamamoto, T., Chiba, N., Magata, F., Takahashi, K., Ueda, If, Sekiya, N .,... Hashimoto, Y. (2011). Joint research onAnshin in Internet usage. NTT Technical Review. Retrieved from https://www.ntt-review.jp/archive/ntttechnical.php7contents =ntr201110fa8.pdf&mode=show_pdf A u t h o r B io g r a p h ie s
Hiromi Moriya is an assistant professor of nursing at Tokai University School o f Health Science. Her research interests include genetic education and genetic counseling. She was responsible for
38
Jo u rn al o f E m p irical R esearch on H u m a n Research Ethics 9 (3 )
the design and implementation of the seminar and contributed to the study design and preparation of the research paper.
Naoaki Ishii is a professor of life-care center at Tokai University School of Medicine. His research interests include preventive medicine, health care, and aging. He was a principal investigator of a clinical study from which the survey participants were recruited and contributed to the study design and preparation of the research paper.
Ituro Inoue is a professor of integrated genetics at National Institute of Genetics. His research interests include genomics of human diseases and ethics in genome research. He advised about the design o f the seminar and the study, and contributed to discus sion of the survey results and brush-up o f the research paper. Mayumi Ikeuchi is an assistant professor of nursing at Tokai University School of Health Science. Her research interests include preventive medicine and health care. She conducted the surveys and discussed the survey results.
Masaru Motojima is an assistant professor of clinical pharmacol ogy at Tokai University School of Medicine. His research interests include developmental biology, congenital kidney anomaly, and research ethics. He was responsible for the design of the study and took the lead in drafting the research paper.
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S u rv e y o f A ttitu d e s o f Japanese W o m e n
Hum an Research Ethics 2014, Vol. 9(3) 2 9-3 8 © The A u th o r(s ) 2014
T o w a r d G e n e tic /G e n o m ic R e s e a rc h
Reprints and permissions: sagepub.com/journalsPermissions.nav D O I: 10.1177/1556264614540597 jre.sagepub.com
DSAGE H ir o m i M o r iy a 1, I t u r o In o u e 2, M a y u m i Ik e u c h i1, N a o a k i Is h ii1, a n d M a s a ru M o t o j i m a 1
A b s tra c t
Previous surveys have suggested th a t e ld e rly Japanese w o m e n have th e lo w e s t scien tific in te re s t and lite ra cy w ith in th e Japanese p o p u la tio n and am ong pop ulatio n s across W e s te rn co u n trie s. Because re c e n t tre m e n d o u s advances in genom e analysis are like ly to be in c o rp o ra te d in to standard b iom edical assessments th ro u g h o u t th e w o rld , w e co n d u cte d surveys to investigate th e a ttitu d e s to w a rd g e n etic/g e no m ic research o f Japanese w o m e n aged b etw e en 55 and 65 years. C u r re n t surveys indicate th a t o b ta in in g adequate in fo rm e d co n se n t fro m e ld e rly Japanese w o m e n is co m p lica te d. T h e lim ita tio n is especially re le va n t to p a rticip a n ts’ lite ra c y in genetics and gen om ic studies. Results o f th e surveys also indicate th a t even a fte r th e in fo rm e d co n se n t is o bta ine d, researchers m u st co n tin u e to supply updated stu dy in fo rm a tio n to th e study subjects, w h ich enables th e m to o bta in a dd itio n a l in fo rm a tio n on th e use o f th e ir samples and g e n etic/g e no m ic in fo rm a tio n . Failure to co n sid e r these o bliga tion s may lead to a loss o f th e p u b lic’s tr u s t and thus a ffe ct research progress on m edical genom ics.
K e y w o rd s
g e n e tic/g e n o m ic research, in fo rm e d consent, Japanese guidelines
In tr o d u c t io n
Surveys conducted by the National Institute of Science and Technology Policy (NISTEP) of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan in 2009 revealed that interest in issues of science and tech nology of Japanese people was lower than that of the United States and the United Kingdom (Second Policy-Oriented Research Group, NISTEP, MEXT, 2011). The surveys also showed that scientific literacy in Japan was the lowest among these countries. Furthermore, women scored lower in both scientific interest and literacy than men across all nationalities. In addition, decline of scientific literacy was observed in the elderly. These findings confirmed earlier surveys conducted in 14 countries, including Japan, the United States, the United Kingdom, and EU members (Second Policy-Oriented Research Group, NISTEP, MEXT, 2002). Together, these observations suggest that elderly Japanese women may be regarded as a group having the lowest scientific interest and literacy. Scientific interest and literacy of elderly Japanese women may play a critical role in shaping their perception of genetic testing and genetic/ genomic research, and in Japanese perception of genetic research generally. How might they wield such influence? In Japanese tradition, mothers are expected to play much greater roles in raising children than those of mothers in
most Western countries because many Japanese believe that it is a mother’s task and that fathers should work hard every day, although this trend may be weakening recently due to increasing number of working mothers. When a baby is born with a genetic disease, the mother bears a huge burden to take care of the child in Japan. In addition, Japanese mothers have been reported to experience extremely high negative pressure from older females as well as other family members if they have a child with a genetic disorder (Kawashima, 1992). Consequently, the perception of genet ics held by elderly Japanese women who have experienced child-raising may affect other family members’ decisions to participate in genetic/genomic research. In this article, we report the findings of surveys that assess basic attitudes of elderly Japanese women toward genetic/genomic research and identify potential obstacles in obtaining effective informed consent. There have been very few studies that specifically investigate attitudes toward genetic research.
'T o k a i U n iv e r s ity , Ise h a ra , Japan N a t i o n a l I n s t it u te o f G e n e tic s , M is h im a , Japan
C o r r e s p o n d in g A u t h o r : M a s a ru M o to jim a , D e p a r t m e n t o f C lin ic a l P h a rm a c o lo g y , S c h o o l o f M e d ic in e , T o k a i U n iv e r s ity , 143 S h im o k a s u y a , Is e h a ra , K a n a g a w a , Japan. E m ail: m - m o to ji@ is .ic c .u - to k a i.a c .jp
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Journal o f Empirical Research on Hum an Research Ethics 9(3)
By comparing the current surveys with previous reports, we can assess the effects of race, gender, and age on attitudes. Moreover, in February 2013, “The Ethical Guidelines for Analytical Research on the Human Genome/Genes” have been jointly renewed by three ministries of Japanese Government: the Ministry of Economy, Trade, and Industry; the MEXT; and the Ministry of Health, Labor, and Welfare of Japan. Many changes in the revised version loosen the requirements for the transfer of stored samples to other institutions. Thus, the revisions may facilitate accumulation of samples in huge repositories. The guidelines, which were originally established in 2002, were intended to serve as a “soft law.” In practice, Japanese researchers generally adhere to the guidelines, because otherwise, they may become the subject of criticism by the Japanese media, lose the trust of the general public, and lose support from the regulatory and funding agencies. Based on results of the current surveys, impacts of the current revisions on require ments for informed consent are discussed.
survey was approved by an institutional review board (IRB) in Tokai University School of Medicine (IRB File 10-206).
M e th o d
The first survey was conducted with 89 Japanese women, 55 to 65 years old (September 2010). The survey was intended to obtain information regarding basic knowledge of genetics and also to assess their primary attitudes toward genetic/genomic research of common diseases. Three months later, a second survey was conducted with the same participants ( n = 85). Before administration of the second survey, a 30-min seminar explaining genetic/genomic research of common diseases was provided by the genome medical research coordinator (H.M.) that simulated the informed consent process to enroll participants. The semi nar covered the following topics: significance of genetic research, genes genome DNA, genes and diseases, method ology of genetic research, interpretation of results of genetic research, and benefits and risks of study participation. The second survey was designed to evaluate alterations in the participants’ attitudes after the seminar, and therefore, con tained more detailed questionnaires. One year later (December 2011), a third survey was con ducted in 105 new participants. This survey was intended to confirm findings of the previous two surveys. Consequently, this third survey combined the questions contained in the prior two surveys, but omitted the complicated questions covered in the previous seminar, as the seminar had not been taken by the new participants. All survey participants were recruited from among sub jects who voluntarily participated in a clinical study titled “An Intervention Study on Excise and Nutrients to Establish a Health Index” conducted by the Life-Care Center, Tokai University School of Medicine. This clinical study aimed to assess the effects of exercise and diet supplements on the health status of healthy Japanese women. The current
R esu lts a n d D iscu ssio n Answers to Questions Regarding Basic Knowledge o f Genetics
In the first survey, 43% of the participants answered that they understood the meaning of the word, “gene” (Table 1, Ql). The rest of the participants had some knowledge about the meaning of the word. Similarly, 51% of the participants understood the meaning of the word, “DNA” (Table 1, Q2), and the rest of the participants had some knowledge about the word. In contrast, only 8% of the participants under stood, and 30% had not heard of the word, “genome” (Table 1, Q3), and therefore, had difficulty understanding the dif ference between gene and genome (Table 1, Q4). In the third survey, 47% understood the meaning of “gene,” 39% understood the meaning of “DNA,” but only 3% understood the meaning of “genome” (Table 3, Q l, Q2, and Q3), thereby, confirming the first-year findings. Whole genome sequencing, also frequently referred to as “personal genome sequencing,” is rapidly being incorporated into routine assessments in clinical research and may bring some new bioethical concerns (Hudson, 2011; Motojima & Ichikawa, 2009; Motojima, Inoue, Yonemoto, & Ichikawa, 2011; van El et al., 2013). In this regard, the meaning of “genome” was too complicated to understand by the survey partici pants and, therefore, may be too complex for subjects in particular studies that involve genetic/genome analysis. Such limitations may become a more urgent concern in an era of whole genome sequencing when obtaining effective informed consent. Some researchers have given up informed consent with adequate understanding (Angrist, 2009). In the second survey, although 54% understood the sem inar well (Table 2, Q13), some participants commented that confidence of their understanding became weaker after the seminar. Therefore, researchers should keep in mind that repeated explanations about genetic/genomic research dur ing the informed consent process are needed until study subjects’ understanding of the genetic/genomic research is assured. Ideally, depending on subjects’ literacy in genetics and genomics, researchers should try not to obtain consent at the first visit and wait until the following visit so as to give them sufficient time to consider the study. Effects o f Inform ation Seminar on Attitudes Toward Genetic!Genomic Research o f Common Diseases
In the first survey, 35% of the participants showed a strongly positive attitude toward participating in genetic research of common diseases (selected “Definitely yes” in Table 1, Q9)
Moriya et al.
31
T a b le I . First Q u e stio n n a ire (Septem ber 2010).
%(n) Q 1. D o you kn o w th e w o rd “ gene” ? Yes 1 do. 1 k n o w th e meaning.
43 (38)
Yes, 1 do. 1 have heard o f it.
57 (51)
No
0 (0 )
Q 2. D o you kn o w th e w o rd “ D N A ” ? Yes 1 do. 1 k n o w th e meaning.
51 (45)
Yes, 1 do. 1 have heard o f it.
48 (43)
No
0 (0 )
Q 3. D o you kn o w th e w o rd “ genom e” ? Yes 1 do. 1 k n o w the meaning.
8 (7 )
Yes, 1 do. 1 have heard o f it.
62 (55)
No
30 (27)
Q 4. Can you distinguish “ gene” fro m “ genom e' 7 Yes 1 can. 1 k n o w th e difference.
6 (5 )
Perhaps
30 (27)
No
64 (57)
Q 5. Have you ever participated in genetic research? Yes No
1 (1) 98 (87)
Q 6. T h e re are a p p roxim ately 22,000 genes in human. G enetic research reveals genes th a t de te rm in e susceptibility to many diseases and tra its such as hypertension, diabetes, and height. D o you w a n t to learn m o re about genes? Strongly positive
37 (33)
Som ew hat positive
53 (47)
N o t sure
7 (6 )
Som ew hat negative
0 (0 )
No
0 (0 )
Q 7. D o you w a n t to kn o w y o u r genotype? Strongly positive
54 (48)
Som ew hat positive
40 (36)
N o t sure
3 (3 )
Som ew hat negative
0 (0 )
N ever 0 (0 ) Q 8. D o you th in k y o u r genetic in fo rm a tio n reflects y o u r fam ily’s a n d /o r relative's inform ation? Yes
94 (84)
No
0 (0 )
1 d o n ’t know .
3(3)
Q 9. W ill you participate in genetic research th a t seeks susceptible genes o f lifestyle diseases such as diabetes, obesity, and hypertension? D e fin ite ly yes
35 (31)
Maybe yes
34 (30)
1 d o n ’t know .
17 (1 5 )
Maybe no
6 (5 )
N ever
0 (0 )
Depends on th e type o f study.
7 (6 )
Note. Participant number: 89.
and 34% were more tentative about participation (selected “Maybe yes”). Overall, almost 70% of the participants showed positive attitudes. Similar results were obtained in the third survey showing that 35% chose “Definitely yes” and 40% chose “Maybe yes” (Table 3, Q9). Positive atti tudes toward participating in genetic research have also been reported from Sweden, Iceland, the United Kingdom, Ireland, the United States, Scotland, Saudi Arabia, and Jordan (Ahram, Othman, & Shahrouri, 2013; Al-Jumah et al., 2011; Johnsson et al., 2010; Treweek, Doney, & Leiman, 2009). After the seminar, the number of strongly positive participants was reduced to 20% (Table 2, Q2) and the number of somewhat negative (from 6% to 12%) and strongly negative participants (from 0% to 1%) doubled indicating that increased knowledge about genetic/genomic research affects decision making. The increased negativity is apparently due to their having realized how knowing their genotype can affect their life and hence, having become anxious about participating in genomic research. In the first survey, most participants showed positive attitudes toward knowing their own genotype (Strongly positive: 54%, Somewhat positive: 40%, Table 1, Q6). This trend was confirmed by the third survey (Strongly positive: 56%, Somewhat positive: 40%, Table 3, Q6). Even after the seminar, almost half of the participants remained interested in obtaining their own test results of genetic/genomic research despite an explanation that results of genetic stud ies mostly provide uncertain results (Everything including uncertain results: 52%, Table 2, Q10). However, the number of participants who showed negative attitudes toward know ing their genotype increased after the seminar, from 0% to 7% (Somewhat negative: 7%, Table 2, Q10). These overall results indicate that understanding of genetic/genome research in elderly Japanese women is rather limited and that it needs to be reinforced with repeated explanations. “The Ethical Guidelines for Analytical Research on the Human Genome/Genes” recommend dis closing results of genetic tests or genome analysis to study subjects. However, when the preliminary results are likely to cause confusion and/or anxiety, researchers can choose not to disclose the results under the new guidelines. Controversy regarding whether and how to disclose research results of genetic analysis have a long history in worldwide ethical debates (Hudson, 2011). When disclosing test results to a subject, a research team needs to consider whether the subject has adequate literacy in genetics/genomics to under stand the test results, and whether disclosure of test results benefits the subject. The research team should provide an opportunity for participants to learn more about genetics/ genomics if the team decides to disclose test results to sub jects with low genetic/genomic literacy. The researchers
32 T a b le 2.
Journal of Empirical Research on Human Research Ethics 9(3) Second Questionnaire After a Seminar (December 2010). % (n)
Q 1. Do you want to learn more about gene, genome, and DNA? 39 (33) Strongly positive 46 (39) Somewhat positive II (9) Not sure 4(3) Somewhat negative No 1 (1) Q2. Will you participate in genetic research if you are asked to join the research? 20 (17) Definitely yes 48 (41) Maybe yes 12 (10) 1don't know. 12 (10) Maybe no Never 1 (1) 5(4) Depends on the type of study. Q3. For participants who answered “ (1) Definitely yes” or “ (2) Maybe yes" in Question 2, please choose the most appropriate reason to participate in the study. 25 (21) The research may improve medicine. 4(3) 1want to cure disease(s) that 1suffer from. 35 (29) 1want to know my susceptibility to diseases. 7(6) 1want to contribute to the progress of science. 1 don’t have any reason to refuse. 1 (1) 0(0) Others Q4. For participants who answered “ (5) Never” or “ (4) Maybe no” in Question 2, please chose the most appropriate reason not to participate in the study. 4(3) 1don’t want to know my susceptibility to diseases. There is a risk of leaking my personal information. 1 (1) 2(2) My susceptibility to diseases may uncover my families’ disease. 1can’t imagine what kind of harm arising from the study. 1 (1) 1can’t understand gene and genome. 3(3) 0(0) Others Q5. For participants who answered “ (6) Depends on the type of study” in Question 2, what kind of study will you participate in? Please specify. Preventive medicine. Future cure of intractable diseases, cancer, etc. Results of the study increase the possibility of prevention or cure of the disease. Studies intend to prevent or cure the disease. Also depend on the type of disease. Q6. Do you think that the explanation provided by study personnel, that is, researcher or research coordinator, is necessary to make your decision to participate in genetic or genome research? 75 (64) Need detailed explanation 24 (20) Need general explanation 0(0) Either will do. 0(0) No Q7. What is the most important factor to make a decision to participate in a genetic study? 39 (33) The research purpose 19(16) Social significance of the study 13(11) Interest in the study 4(3) Reliability of the study personnel 0(0) Personality of the study personnel 16(14) Your own benefit (cure your disease, etc.) 5(4) Opinion of family members 2(2) Others (continued)
Moriya et at.
33
T a b le 2. (continued)
% (n) Q 8. Degree o f im p orta n ce o f fo llo w in g issues in explanations o f genetic study (5 -p o in t scale): I = unimportant. 2 = slightly important, 3 important, 4 = very important, 5 = critical 5
4
3
Basic explanations a b o ut genes, genom e, and research.
48 (41)
25 (21)
1 8 (15)
1 (1)
1 (1)
Explanations on the disease o f th e study.
58 (49)
30 (25)
9 (8 )
1 (1) 0 1 (1) 0
2
1
Explanations about the relation betw een the disease and the gene.
58 (49)
31 (26)
7 (6 )
1 (1) 2 (2 )
Explanations a b o ut study m ethods.
51 (43)
25 (21)
1 9 (16)
2 (2 )
Explanations on th e handling o f personal info rm a tio n .
75 (64)
I I (9)
I I (9)
Explanations o f th e handling o f genetic in fo rm a tio n , medical records, blo o d samples.
72 (61)
1 8 (15)
8 (7 )
1 (1) 0
D isclosure o f study results.
58 (49)
22 (19)
I I (9)
5 (4 )
0
Explanations on benefits o f the study p articipation.
50 (42)
25 (21)
21 (18)
0
Explanations on risks o f th e study participation.
59 (50)
2 2 (1 9 )
1 5 (13)
1 (1) 0
Freedom to w ith d ra w a l fro m th e study.
58 (49)
25 (21)
I I (9)
4 (3 )
0
0
0
Q 9. H o w long do you w a n t to hear about the genetic study w hen you are asked to participate i Less than 5 min 5-10 min
0( 0) 1 4 (12)
10-30 min
1 4 (12)
30-60 min
60 (41)
M ore than 60 min
2 2 (1 9 )
Q 10. If you participate in a genetic study, do you w a n t to kn o w yo u r genotype, although the link betw een genotype and disease may be unclear? Everything including uncertain results
52 (44)
O n ly validated results
34 (29)
E ither w ill do
6 (5 )
Som ew hat negative
7 (6 )
N e ve r
0 ( 0)
Q I I . If a m uta tio n th a t causes a serious disease is found by chance, do you w a n t to be inform ed? Yes
65 (55)
Yes, b u t only in case th e re is a therapy o r prevention
29 (25)
No
I (I)
N o , b u t te ll the resu lt to m y fam ily o r hom e d o c to r
2 (2)
O th e rs (I) Q 1 2. If y o u r sample is used fo r a new study th a t was n o t explained d u ring th e initial in form ed consent, do you wish to participate in th e study? Yes, 1 do.
18 (1 5 )
Yes, b u t 1 re s tric t th e use o f my sample to th e study.
1 0 (9 )
Yes, b u t 1 need to be inform ed as to w h a t is the in te n t o f the study.
40 (34)
Yes, b u t com m unicate w ith me a b o ut w h a t study it is to be used by In te rn e t o r a p o ste r in the hospital.
1 (1)
Yes, b u t my sample should be com pletely anonymous.
15 (1 3 )
N o , 1 d o n ’t.
13 (1 1 )
O th e r
2 (2 )
Q I3 . D id you understand to d ay’s seminar well? Yes, 1 u n d ersto o d it com pletely.
16 (1 4 )
Yes, 1 u n d ersto o d it well.
38 (32)
H alf o f it.
3 6 (3 1 )
N o t so well.
6 (5 )
N o t a t all.
0 (0 )
Note. Participant number: 85.
34
Journal o f Empirical Research on Hum an Research Ethics 9(3)
Table 3.
Third Questionnaire of New Volunteers (December 2011, Second Year). % (n)
Q 1. D o you know the w o rd “ gene” ? Yes 1do. 1 know the meaning.
47 (49)
Yes, 1 do. 1have heard o f it.
53 (56)
No
0 (0 )
Q2. Do you know the w ord “ D N A ” ? Yes 1do. 1 know the meaning.
39 (41)
Yes, 1 do. 1have heard o f it.
58 (61)
No
1 (1)
Q3. D o you know the w ord “ genome” ? Yes 1do. 1 know the meaning.
3(3)
Yes, 1 do. 1have heard o f it.
69 (72)
No
29 (30)
Q4. Can you distinguish “ gene” from “ genome” ? Yes 1can. 1 know the difference. Perhaps
1 (1) 28 (29)
No
70 (74)
Q5. Have you ever participated in genetic research? Yes Never
1 (1) 98 (103)
Q6. There are approximately 22,000 genes in human. Genetic research reveals genes that determine susceptibility to many diseases. Do you want to learn m ore about genes? Strongly positive
31 (33)
Somewhat positive
58 (61)
N o t sure
8 (8 )
Somewhat negative
2 (2 )
Never
0 (0 )
Q7. D o you want to know your genotype? Strongly positive
56 (59)
Somewhat positive N o t sure
40 (42)
Somewhat negative
1 (1) 0 (0 )
Never
2 (2 )
Q8. Do you think your genetic information reflects your family’s information? Yes
94 (99)
No
2 (2 )
1don’t know.
1 (1) Q9. W ill you participate in genetic research that seeks susceptible genes o f lifestyle diseases such as diabetes, obesity, and hypertension? 35 (37) Definitely yes Maybe yes
40 (42)
1do n't know.
19 (20) 4 (4 )
Maybe no Never
0 (0 )
Depends on the type o f study.
2 (2 ) QIO. For participants w ho answered “ (1) Definitely yes” o r “ (2) Maybe yes” in Question No. 9, please choose the most appropriate reason to participate in the study. 21 (22) The research may improve medicine. 1want to cure disease(s) that 1 suffer from. 1want to know my susceptibility to diseases. 1want to contribute to the progress of science. 1don’t have any reason to refuse. Others
5 (5 ) 47 (49) 2 (2 ) 2 (2 ) 0 (0 ) (continued)
Moriya et al.
35
T a b le 3. (continued)
__________________________________ %(n) _________ Q I I . For participants w ho answered “ (5) N ever” o r “ (4) Maybe no” in Question 9, please choose the most appropriate reason not to participate in the study. I don’t want to know my susceptibility to diseases.
2 (2)
There is a risk o f leaking my personal information.
0 (0)
My susceptibility to diseases may uncover my families’ disease.
0 (0)
I can’t imagine what kind of harm w ill arise from the study.
0 (0)
I can’t understand gene and genome. O thers
0 (0) |
Q 12. For participants w ho answered “ (6) Depends on the type o f study" in Question 9, what kind o f study w ill you participate in? Does not cause mental stress N o answer Q 1 3. D o you want to learn more about gene, genome, and DNA? Strongly positive
27 (28)
Somewhat positive
60 (62)
N o t sure
8 (8)
Somewhat negative
2 (2)
No
0 (0)
Q I4 . D o you think that the explanation by the study personnel is necessary to make your decision to participate in genetic o r genome research? Need detailed explanation Need general explanation
84 (88)
10 ( 10) 2 (2) 0 (0)
Either w ill do. No Q 1 5. W h a t is the most im portant factor to make a decision to participate in a genetic study? The research purpose
55 (58)
Social significance o f the study
12(13)
Interest in the study
15(16)
Reliability o f the study personnel
3 (3 )
Personality of the study personnel
0 (0 )
Y our own benefit (cure your disease, etc.) Opinion of family members
6 ( 6)
O thers
0 (0 )
3(3)
Q 1 6. H ow long do you want to spend to hear about the genetic study when you are asked to participate in? Less than 5 min 5-10 min
0 ( 0) 4 (4 )
10-30 min
13(14)
30-60 min
49 (51)
More than 60 min
29 (30)
Q 1 7. If a mutation that causes a serious disease is found by chance, do you want to be informed? Yes
90 (94)
Yes, but only in case there is a therapy o r prevention. No
5 (5 )
No, but tell the result to my family o r home doctor. Others
I (I) 0 (0 )
I (I)
Note. Participant number: 105.
may consult with the IRB for additional guidance; many Japanese institutions have IRB members specializing in reviewing genetic/genomic research. In the second (post-seminar) survey, 65% of the partici pants wished to be informed about incidental findings that
cause serious diseases regardless of an available cure or pre vention, whereas 29% wanted to be informed about inciden tal findings only if a cure or prevention is available (Table 2, Q11). In the third survey, 90% wished to be informed of incidental findings, and only 5% wished to be informed
36
Journal o f Empirical Research on H um an Research Ethics 9(3)
when prevention or cure is available (Table 3, Q17). Therefore, the seminar may have increased participants’ understanding of a “right not to know” and the limitations of genetic/genomic findings. However, the majority of the survey participants still wished to know incidental findings regardless of prevention or cure. Researchers or professional geneticists may overestimate public understanding of genetics and genomics (Condit, 2010). Disclosing incidental findings to study subjects with out adequate explanation and genetic counseling may cause unnecessary anxiety especially when their literacy in genet ics and genomics is low. It is therefore recommended that during informed consent, researchers provide sufficient explanations about types of incidental findings that may emerge, including the chance of prevention and/or the avail ability of therapy of the particular disease especially when subjects’ literacy in genetics and genomics is low.
study is disclosed to the public by an Internet website or a poster in the responsible hospital. According to our second survey, if the survey participants were asked to donate their DNA samples for a study that was not specified in the con sent form, only 1% of them would agree to the use of their samples without re-consent for a new study even when information on the study is disclosed by Internet or posters in responsible hospitals (Table 2, Q12). The Japanese ethical guidelines have shifted toward shared use of DNA samples, genetic/genomic information, and medical records to promote deposits from institutions to huge repositories. In the previous guidelines, when a researcher transfers research participants’ samples and ano nymized medical records to other institutions, the samples and medical records need to be completely de-identified by removing all personal identifiers. The revised guidelines permit retention of a correspondence table that enables link age of personal information and a code replacing personal identifiers in a sample and clinical information. It also per mits obtaining so-called “broad consent” for future studies. Thus, repositories that collect DNA/tissue samples and medical records of research participants can update partici pants’ medical records in ongoing and future studies. It is probable that in the future, DNA samples, genetic/genomic information, and medical records of study subjects will be used in research that the subject never imagined. The cur rent surveys demonstrate that regarding the use of samples for a new study, 10% preferred restricting the use to the study indicated, 40% requested researchers to inform them directly about the purpose of the new study, 15% refused to take part in the study, and 13% accepted only if the samples are fully de-identified to disconnect them from their per sonal information (Table 2, Q12). Thus, the majority of the survey participants reveal a preference to be directly informed as to what studies their samples and information will be used. This attitude of the survey participants may not be limited to elderly Japanese women. In a survey con ducted in New York, more than 60% of the participants felt uncomfortable with the use of their samples in a new study and worried about the new study (Kerath et al., 2013). In a survey conducted in Finland, one third would require re consent for every new study and 44% would like to limit the use of their samples (Tupasela et al., 2010).
Responses to Questions Regarding Informed Consent In the second survey after the seminar, 75% of the partici pants requested detailed explanation of the genetic research when they were asked to participate in a research project (Table 2, Q6). Although the adequacy of explanation is often a qualitative matter, it is necessary to devote sufficient time to ensure adequate understanding of the scientific con cepts. Because 60% of the participants chose 30 to 60 min as appropriate time to spend for the explanation (Table 2, Q9), this implies a 30- to 60-min informed consent process. In the third survey, 30 to 60 min was also the most preferred duration of time for the explanation (49% chosen, Table 3, Q16). Therefore, it appears that 30 to 60 min is recognized as an appropriate time length to understand issues of the informed consent by elderly Japanese women. To assess the concerns about participating in a genetic study, we asked the survey participants to rank the impor tance of issues explained (Table 2, Q8). Handling personal information (75% chose “Critical”) as well as genetic infor mation, medical records, and samples (72%) was identified as the most important issue, indicating that the major con cern of the survey participants is how the confidentiality of their personal information and samples is protected and secured. Similarly, in a survey conducted in New York, a major reason for refusing to participate in a huge repository of DNA and health records was personal privacy (Kerath et al., 2013). Of note, a recent survey comparing 10 differ ent countries showed that the Japanese population, includ ing both men and women, was most concerned about protecting personal information (Yamamoto et al., 2011). In the Japanese ethical guidelines, researchers are allowed to use genome DNA samples without obtaining re consent when meeting all of the following conditions: (a) It is impossible to obtain re-consent from the subjects, (b) the IRB approves the use, and (c) the information on a new
Conclusion The surveys indicated limited understanding of genetic con cepts in elderly Japanese women. However, their attitudes toward genetic research were similar to previous reports from other countries. Best Practices Researchers may need to provide extensive, and even redun dant, explanations about genetic/genomic research to obtain
Moriya et al.
adequate informed consent. They should provide genetic counseling if results or incidental findings are to be returned to study subjects. And they should provide updated informa tion when donated samples are to be re-used in new studies. Research Agenda
Further research is needed to assess how their knowledge of genetics/genomics, age, and gender affects their attitudes toward genetic/genomic research. We also need to clarify what knowledge of genetics/genomics are required for adequate decision making to participate in genetic/genomic research. E ducational Im plication
IRB members and researchers need to be taught about basic genetics/genomics and research ethics. A c k n o w le d g m e n t
The authors thank Dr. Valentina Kon, Vanderbilt University, for advice and comments on the article. D e c l a r a t i o n o f C o n f l ic t i n g In t e r e s t s
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. F u n d in g
The author(s) received no financial support for the research, authorship, and/or publication of this article.
R e fe re n c e s
Ahram, M., Othman, A., & Shahrouri, M. (2013). Public support and consent preference for biomedical research and biobank ing in Jordan. European Journal o f Human Genetics, 21, 567570. doi: 10.1038/ejhg.2012.213 Al-Jumah, M., Abolfotouh, M. A., Alabdulkareem, 1. B., Balkhy, H. H., Al-Jeraisy, M. I., Al-Swaid, A. F., . . .Al-Knawy, B. (2011). Public attitude towards biomedical research at outpa tient clinics of King Abdulaziz Medical City, Riyadh, Saudi Arabia. East Mediterranean Health Journal, 17, 536-545. Angrist, M. (2009). Eyes wide open: The personal genome project, citizen science, and veracity in informed consent. Personalized medicine, 6, 691-699. doi: 10.2217/pme.09.48 Condit, C. M. (2010). Public understandings of genetics and health. Clinical Genetics, 77, 1-9. doi: 10.111 l/j. 13990004.2009.01316.x Hudson, K. L. (2011). Genomics, health care, and society. New England Journal o f Medicine, 365, 1033-1041. doi: 10.1056/ NEJMral010517 Johnsson, L., Helgesson, G., Rafnar, T., Halldorsdottir, I., Chia, K. S., Eriksson, S., & Hansson, M. G. (2010). Hypothetical and factual willingness to participate in biobank research. European Journal o f Human Genetics, 18, 1261-1264. doi: 10.1038/ejhg.2010.106
37 Kawashima, H. (1992). Different client's response at genetic clinics in Japan and the USA, and its ethical background. In N. Fujiki & D. R. J. Macer (Eds.), Human Genome Research and Society: Proceedings of the Second International Bioethics Seminar in Fukui, Eubios Ethics Institute (pp. 145146). Retrieved from http://www.eubios.info/HGR.htm Kerath, S. M., Klein, G., Kern, M., Shapira, I., Witthuhn, J., Norohna, N., . . .Taioli, E. (2013). Beliefs and attitudes towards participating in genetic research— A population based cross-sectional study. BMC Public Health, 13, Article 114. doi:10.1186/1471-2458-13-114 Motojima, M., & Ichikawa, I. (2009). The impact of recent revisions in the Japanese Ethical Guidelines for Clinical Research. Asian Bioethics Review, 1, 329-341. doi: 10.1353/ asb.2009.0003 Motojima, M., Inoue, I., Yonemoto, S., & Ichikawa, I. (2011). Progress in human genome research prompts a paradigm shift in research ethics. Rinsho Hyoka (Clinical Evaluation), 38, 855-867. Second Policy-Oriented Research Group, National Institute of Science and Technology Policy, Ministry of Education, Culture, Sports, Science and Technology. (2002). The 2001 survey fo r public attitudes towards and understanding o f science & technology in Japan. Retrieved from http://www .nistep.go.jp/achiev/sum/eng/rep072e/rep72se.pdf Second Policy-Oriented Research Group, National Institute of Science and Technology Policy, Ministry of Education, Culture, Sports, Science and Technology. (2011). International comparison o f the public attitudes towards and understanding o f science and technology: Comparative study o f internet survey in Japan, the United States o f America, and the United Kingdom. Retrieved from http://www.nistep.go.jp/ achiev/abs/eng/mat 196e/pdf/mat 196ae.pdf Treweek, S., Doney, A., & Leiman, D. (2009). Public attitudes to the storage of blood left over from routine general prac tice tests and its use in research. Journal o f Health Service Research Policy, 14, 13-19. doi: 10.1258/jhsrp.2008.008016 Tupasela, A., Sihvo, S., Snell, K., Jallinoja, P., Aro, A. R., & Hemminki, E. (2010). Attitudes towards biomedical use of tissue sample collections, consent, and biobanks among Finns. Scandinavian Journal o f Public Health, 38, 46-52. doi: 10.1177/1403494809353824 van El, C. G., Cornel, M. C., Borry, P., Hastings, R. J., Fellmann, F., & Hodgson, S. V., . . . ESHG Public and Professional Policy Committee. (2013). Whole-genome sequencing in health care: Recommendations of the European Society of Human Genetics. European Journal o f Human Genetics, 21, 580-584. doi: 10.1038/ejhg.2013.46 Yamamoto, T., Chiba, N., Magata, F., Takahashi, K., Ueda, If, Sekiya, N .,... Hashimoto, Y. (2011). Joint research onAnshin in Internet usage. NTT Technical Review. Retrieved from https://www.ntt-review.jp/archive/ntttechnical.php7contents =ntr201110fa8.pdf&mode=show_pdf A u t h o r B io g r a p h ie s
Hiromi Moriya is an assistant professor of nursing at Tokai University School o f Health Science. Her research interests include genetic education and genetic counseling. She was responsible for
38
Jo u rn al o f E m p irical R esearch on H u m a n Research Ethics 9 (3 )
the design and implementation of the seminar and contributed to the study design and preparation of the research paper.
Naoaki Ishii is a professor of life-care center at Tokai University School of Medicine. His research interests include preventive medicine, health care, and aging. He was a principal investigator of a clinical study from which the survey participants were recruited and contributed to the study design and preparation of the research paper.
Ituro Inoue is a professor of integrated genetics at National Institute of Genetics. His research interests include genomics of human diseases and ethics in genome research. He advised about the design o f the seminar and the study, and contributed to discus sion of the survey results and brush-up o f the research paper. Mayumi Ikeuchi is an assistant professor of nursing at Tokai University School of Health Science. Her research interests include preventive medicine and health care. She conducted the surveys and discussed the survey results.
Masaru Motojima is an assistant professor of clinical pharmacol ogy at Tokai University School of Medicine. His research interests include developmental biology, congenital kidney anomaly, and research ethics. He was responsible for the design of the study and took the lead in drafting the research paper.
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