- Kaede Tomoeda, M.D., Ichiro Matsuda, M.D., Ph.D.
Dept. Pediatrics, Kumamoto University School of Medicine
Honjo 1-1-1, Kumamoto City 860-8556 JAPAN
Eubios Journal of Asian and International Bioethics 8 (1998), 75-76.
The favorable results in PKU screening in USA and other countries, including Japan, led to an increase of the number of the diseases which qualified for NMSP. In 1989 these were maple syrup urine disease, homocystinuria, galactosemia, hypothyroidism and 21-hydroxyase deficiency. Some of these disorders are important public health concerns, even in developing countries. NMSP has been playing an important role in child health care systems in Japan since 1970. In Japan, almost all newborns are being tested under NMSP. It has become an essential part of our country's health program.
As has been discussed in other fields of medicine, NMSP in Japan also requires a new view based on biomedical ethics. There are several ethical issues that need to be resolved:
(1) Most diseases under NMSP are genetic ones, therefore, genetic aspects of the diseases should be explained to the family in the case of a positive test (President's Commission Report in USA, 1983).
It is generally accepted that genetic tests be done after acquisition of written informed consent (Holtzman, 1989), the only exception being the lack of competence such as in minors. In such cases, a proxy consent should be obtained from biological parents or legal guardians, and the content of decision should be based on only the interest of such persons (Wertz et al. 1995, Matsuda et al. 1997). In many states in the USA, NMSP has been conducted on a mandatory rather than a voluntary basis. The reason for such management is that a refusal of the newborn screening test by a proxy could result in an inescapable disadvantage to some newborns, since they may lose the opportunity to be treated at an early stage for a disease detectable in NMSP. Thus, refusal of a screening test by parents is thought to be against the principle of nonmaleficence in biomedical ethics (Beauchamp and Childress, 1989), and coercion of the management could occur. Equal access to screening for infants is another reason for such management. In Japan, NMSP has been carried out on voluntary grounds, but in reality has been done on mandatory grounds. In some countries like in Denmark, the screening is not mandatory, but very few of the newborns are not tested (Pederson, personal communication). Nevertheless, information of NMSP should be given to parents prior to the blood sampling of newborns.
Things could change in the future, if NMSP is to include intractable diseases, such as fragile X syndrome, Duchenne muscle dystrophy, or disease for which there is no clear therapy. Written informed consent/refusal is necessary for screening in such cases.
(2) NMSP may require additional aspects of macro-biomedical ethics, similar to epidemiological studies, which differs from micro-biomedical ethics that concentrates on the standpoint of the individual. While, considering both aspects, the confidential data on affected babies needs to be protected (Bankowski et al. 1991).
To confirm the suspected disease, newborns should be sent to pediatricians with sufficient knowledge of the disease and experience to treat them appropriately. When a positive diagnosis is given, then the true reciprocity of physician-patient (parents) relationship can be established, where genetic counseling, in addition to therapy, is an obligation. It should be noted, however, that parents have a right to know or not to know. Therefore, a careful approach is essential, as suggested in the guidelines proposed by WHO (1995) and the Japan Society of Human Genetics (JSHG, 1997). Information must be protected by confidentiality. However, retrospective follow-up studies of each case are necessary, and the collected data will aid in treating the affected subjects, at present and in the future. Thus, arrangement to protect privacy of these patients, for example, collecting clinical records with subjects given coded numbered should be considered to protect individual identity (Bankowski et al. 1991).
(3) Cost/benefits, cost/effectiveness and cost/utility (distributive justice, under principles of the biomedical ethics by Beauchamp and Childress, 1989) are other issues for evaluating NMSP. Especially when new diseases or new screening methods are proposed in NMSP, using official resources, it is important that scientific significance, safety and limitation, cost/effectiveness, cost/benefits and cost/utility in the attempt should be confirmed by pertinent pilot studies.
(4) How to legally re-use samples collected by NMSP for other purposes (Laberge, 1994).
Generally, blood samples provided in NMSP should be used only for the original purpose, but could be used for anonymous research or surveillance, when the following conditions are proved: (1) a regional ethical committee or an ethical committee of the Japan Society of Newborn Mass Screening is informed that such studies are being conducted, (2) samples are anonymous and unlinked to avoid possible individual or population discrimination, and (3) conducted studies using left over samples should be available only for supporting development of medical science and benefits to the society.
To ensure the rights of the patient and family when performing mass screening tests and handling of the test samples, guidelines were prepared by the Japan Society of Mass Screening in 1997 (President: Shouichi Sakamoto, M.D., Ph.D.). This is as follows:
Guidelines on Mass Screening
1. Performing currently accepted mass screening programs
1) Neonatal or infant mass screening requires voluntary consent from the guardian. A thorough explanation of the purpose and other information of the test must be given before consent. Refusal to be screened must not bring unjust disadvantages.
2) Test results and information of the individual are protected under confidentiality rights unless there is a substantial reason [*See 'Guidelines prepared by the Japan Society of Human Genetics, 1997.]. If clinical information of the individual is given anonymously for retrospective epidemiological or follow-up studies, a signed document is unnecessary, but informing the guardians in advance is advised. Both research projects are indispensable in achieving the original goal of mass screening.
3) Samples for screening must not be used for other purposes. However, if it applies to both of the following, the sample may be used for research after being approved by the ethical committee of the Institute of the researcher (or by the Japan Mass Screening Society's Ethics Committee) and by the prefecture (Mass Screening Committee).
a) The purpose of the project/research is advancement in medicine.
b) The sample is anonymous and all identifiable characterizations are concealed.
2. Research and development in new mass screening tests.
1) Consent from the Japan Mass Screening Society Ethics Committee or from the Mass Screening Committee of the prefecture is necessary to perform experimental studies for the establishment of new mass screening tests. Consent from the guardian following a thorough explanation of the purpose and the procedure (informed consent) must precede the test.
2) Issues concerning 'test results and information of the individual' and 'handling of test samples' are consistent with items 2) , 3) of performing currently accepted mass screening programs as mentioned above.
3. Initiation of a new mass screening test using public funds requires sufficient results from an experimental study. The study must include analysis of the risks, effectiveness (both for testing and treatment), validity (availability of other methods), review of its necessity and cost effectiveness.
1. Bankowski Z, Bryant J H, Last J M, Ethics and Epidemiology: International Guidelines, CIOMS, 1991.
2. Beachamp T L and Childress J F, Principles of Biomedical Ethics, (4th ed.),Oxford University Press, 1994.
3. Holtzman N A, Proceed with Caution - Predicting genetic risks in the recombinant DNA era, John Hopkins University Press, 1989.
4. Laberge C, Public health rational for newborn screening and civic values, in New Horizons in Neonatal Screening (eds Farrisux I P and Dhondt J P), International Congress Series 1041, Excepta Medica, Amsterdam, 1994.
5. Matsuda K, Satoh K, Suzumori K, Niikawa N, Fukusima Y, Fuziki N, Miwa S., Guideline for genetic counselling and prenatal diagnosis - JSHG, 1994, Jpn J Human Genet, 142: 375-377.1997 [also in EJAIB].
6. Matsuda I, Satoh K, Suzumori K, Niikawa N, Fukusima Y, Fuziki N, Matsui I, Kanazawa I, Tsuji S, Miwa S, Guideline for genetic testing, using DNA analysis - JSHG, 1995, Jpn J Human Genet, 142: 377-379, 1997 [also in EJAIB].
7. President's Commission for the Study of Ethical Problems in Medicine and Behavioral Research: Screening and counselling for genetic conditions, A report on the ethical social, and legal implications of genetic screening, counselling and education programs. USA Government Printing Office, Washington DC, 1983.
8. Wertz D C, Fletcher J C, Berg K, Bouljenkov V, Guidelines on ethical issues in medical genetics and the provision of genetic services. WHO, 1995.