- Email: [email protected]
Very High Compliance in an Expanded MS-MS-Based Newborn Screening Program despite Written Parental Consent
Preventive Medicine 34, 127–131 (2002) doi:10.1006/pmed.2001.0952, available online at http://www.idealibrary.com on
Very High Compliance in an Expanded MS–MS-Based Newborn Screening Program despite Written Parental Consent Bernhard Liebl, M.D.,*,1 Uta Nennstiel-Ratzel, M.D., M.P.H.,* Ru¨diger von Kries, M.D.,† Ralph Fingerhut, Ph.D.,‡ Bernhard Olgemo¨ller, M.D., Ph.D.,‡ Andreas Zapf, M.D.,§ and Adelbert A. Roscher, M.D.¶ *Public Health Newborn Screening Center of the State of Bavaria, Landesuntersuchungsamt Su¨dbayern, D-85762 Oberschleissheim, Germany; †Institute for Social Pediatrics and Adolescent Medicine and ¶Children’s Hospital, University of Munich, Munich, Germany; ‡Labor Becker, Olgemo¨ller & Kollegen, Munich, Germany; and §Bavarian State Ministry of Health, Munich, Germany Published online December 20, 2001
Objectives. In Bavaria, Germany, an expanded MS– MS-based newborn screening program was implemented in 1999. The coverage of new additional conditions and novelty of technology required introduction of written parental consent. Here we evaluated the influence of the consent procedure on compliance by systematic demographic tracking. Methods. Comprehensive information was provided for parents, professionals, and the public. Screening notifications were matched with all birth notifications on name and date of birth. Parents of children without screening notification were contacted and counseled. Results. Between August 1, 1999, and July 31, 2000, 123,284 children eligible for screening were born. Of these, 116,652 were matched successfully. Among 6,632 parents contacted, 2,516 (2%) did not respond. Three thousand thirty-four children were screened but the parents initially refused to participate in tracking. Five hundred ninety-four were screened outside the program. Four hundred eighty-eight untested newborns were identified. Three hundred twenty-five screening failures due to logistic problems were tested subsequently. Screening was definitely refused by the parents of 163 children (0.1% of target population). Conclusions. With appropriate information provided and surveillance by tracking, high compliance with newborn screening can be achieved despite a written consent requirement. 䉷 2001 American Health Foundation and Elsevier Science (USA)
1
To whom correspondence and reprint requests should be addressed at the Public Health Newborn Screening Center of the State of Bavaria, Landesuntersuchungsamt Su¨dbayern, D-85762 Oberschleissheim, Germany. Fax: ⫹⫹49-89-31560-458. E-mail: [email protected].
Key Words: newborn screening; tandem mass spectrometry; consent; tracking.
INTRODUCTION
Tandem mass spectrometry (MS–MS) is a both promising and challenging new technology that has began to have significant impact in newborn screening. MS– MS is a highly sensitive and specific method to detect phenylketonuria (PKU). Compared with previously used diagnostic methods (e.g., bacterial inhibition assay, fluorometric assay) screening can be performed earlier and with lower false positive rates [1–3]. In addition to PKU, MS–MS allows one to screen for further disorders in the same analytical run without significant additional test costs. Among these are maple syrup urine disease (MSUD) [4], homocystinuria [5], and medium chain acyl-CoA dehydrogenase (MCAD) deficiency [6], as well as at least a dozen other disorders in amino, organic, and fatty acid metabolism [7]. Although very few of the diseases likely to be detected by MS–MS are regarded as completely untreatable, the long-term outcome in some of the more severe forms is dubious [8]. There are controversial views over screening for such diseases. One opinion is that early knowledge of a poorly or even untreatable serious disorder might cause more harm than good [9]. Another point of view is that under the provision of minor technical risk perfect treatment options are not a prerequisite as long as the affected newborn may benefit. Furthermore, parents usually want to be informed about the child’s problems as soon as possible [10,11]. It even can be argued that there is a “right” to information and that withholding information is an unjustifiable form of medical paternalism [12].
127
0091-7435/01 $35.00 䉷 2001 American Health Foundation and Elsevier Science (USA) All rights reserved.
128
LIEBL ET AL.
In this context the question of adequate pretest counseling and consent arises. There is disagreement in the ethical and legal literature as to whether parents should have the right to refuse “standard health care” that might benefit their child, e.g., screening for PKU [13–15]. On the other hand, they have a clear right to refuse screening that is being done primarily for the benefit of the family [16]. The traditional parental “informed refusal” approach may be acceptable for screening for some of the diseases detectable by MS–MS (e.g., PKU). However, when disorders for which evidence for effective treatability is incomplete are included, individualized informed consent must be obtained [17]. Unlike screening programs in other countries, in Germany screening has always been regarded as a medical act. Participation is voluntary, even for basic tests such as for PKU and congenital hypothyroidism (CH), though there has been no clear policy on the question of individual counseling and consent. In the state of Bavaria (120,000–130,000 births per annum) [18], a prospective MS–MS-based model program was implemented in 1999 following an intense medical, ethical, and legal debate. Adequate pretest information and written consent by the parents were required for participation in the program extended to screening for MSUD; homocystinuria; MCAD deficiency; glutaric acidemia type I; propionic, methylmalonic, and isovaleric acidemia; and other diseases investigated under research conditions. Non-MS–MS-based tests are used to screen for CH, congenital adrenal hyperplasia (CAH), biotinidase deficiency, and galactosemia. A comprehensive information strategy assisted by a demographic tracking system was introduced to ensure high quality of the entire screening process. The goal was to ensure equitable access and to attain the highest level of voluntary compliance possible. The aim of this study was to find out whether a high compliance with the screening program can be achieved despite the move to written parental consent. METHODS
Information Policy With the increasing number of diseases being covered by the screening program and the need for written consent, information strategy has become increasingly important. Policies were designed and approved by appropriate scientific, ethical, and legal committees. Detailed written information on the individual tests, interpretation of results, and the various disorders screened for is summarized in a screening manual for professionals. A leaflet for health care workers was designed as short information for all those taking specimens (physicians, midwives, nurses) and to assist pretest counseling. A parent information pamphlet and consent sheet provides additional written information about the aims
of the program, the test procedures applied, and the features and consequences of the defects that may be identified. Two forms of written parental consent were asked for independently: (1) for taking part in the laboratory investigations as a whole (expanded MS–MSbased screening as well as basic tests such as for PKU, CH, CAH, biotinidase deficiency and galactosemia) and (2) for transmission of personal data to the state screening center for the purpose of demographic tracking facilitating quality assurance of the entire screening process. Parents are given three alternatives to sign the consent form accompanying the information pamphlet: (1) consent to both the laboratory investigations and the data transmission from the laboratory to the public health services, (2) consent to only the laboratory investigations and not to data transmission, and (3) refusal of newborn screening. The form signed by one of the parents stays with the patient record held by the specimen submitter. The submitter marks the parents’ choice (alternative 1 or 2) on the screening card. A telephone inquiry service for all participants (health care workers and parents) has been established for assistance for all questions concerning the program. Through this central service senders of blood samples and attending physicians can also ask for screening results of children in their care. Program-specific education of medical personnel was simultaneously intensified by teaching at midwife and public health schools. Half-yearly newsletters reporting on the progress of the program, detection rates, and difficulties and problems are distributed to all participants. The public is regularly informed by interviews, reports, and official statements in the media (TV, radio, press). Demographic Tracking All procedures involved in this system were approved by the Bavarian data protection commissioner. The laboratory service, the state screening center, and the regional public health offices cooperate to ensure that the new expanded program is offered to every baby in Bavaria (Fig. 1). Those who do not wish to participate in this state-supported program can obtain newborn screening at some private laboratory services still offering less comprehensive programs. All demographic data of the children screened within the statesupported program are recorded electronically by the laboratory. In the case of parental consent to participate in tracking, these data are transmitted electronically to the state center. This center arranges the data according to place of residence and generates individual lists with names and dates of birth (no results) of tested newborns for each of the 76 regional public health offices covering the entire state territory (71,000 km2) [18]. The regional public health offices receive these
129
CONSENT IN NEWBORN SCREENING
FIG. 1. Demographic tracking. Scheme of information flow.
lists on a weekly basis and match them with the birth notifications in their region. In Bavaria, registration offices report birth notifications to public health offices in the areas of the newborns’ residences. This was already established before implementation of the newborn screening tracking system for the purpose of health consultation of families. The parents of children missing on the screening lists are contacted individually. The reasons may be (1) procedural failures (e.g., lost specimens), (2) refusal of data transmission, (3) screened outside the program, or (4) refusal of screening. If screening cannot be confirmed the parents are again specifically counseled on the importance of newborn screening. The personal data are extinguished immediately after matching, at the latest 6 weeks after receipt. On a monthly basis, the regional public health offices report anonymous statistical data on the results of follow-up to the state screening center. RESULTS
Between August 1, 1999, and July 31, 2000, 123,284 children eligible for screening were born (Table 1). Of these, 116,652 newborns were successfully matched on name and date of birth. Parents of 6,632 newborns had to be contacted by regional public health workers because the names of their children were missing on the
TABLE 1 Results of Demographic Tracking in Bavaria from August 1, 1999, to July 31, 2000
Notified births First 3 days deaths Target population Successfully matched (Names of screened newborns against birth notifications) Parental contact by regional public health offices (due to missing names on screening lists) Positive parental response to contact by regional public health office Results Screened Within model program, data transmission to state center refused Outside model program Untested “Human errors”: misunderstandings, lost samples, etc. (subsequently screened) Screening refused Screening confirmed No parental response to contact by regional public health office (screening status uncertain)
N
% of target population
123,490 206 123,284
100%
116,652
94.6%
6,632
5.4%
4,116
3.3%
3,034 594
2.5% 0.5%
325 163 120,605
0.3% 0.1% 97.8%
2,516
2.0%
130
LIEBL ET AL.
screening lists. In 4,116 cases (62% of parental contacts) the parents responded so that the reason for the names of their children missing on the screening lists could be clarified. There were 3,034 children who had been screened, but the parents had refused to identify to the screening center. Five hundred ninety-four children had been screened by other programs, mostly because of delivery outside the state of Bavaria. Four hundred eighty-eight untested newborns were identified. Missing screening in 325 of these (0.3% of the target population) was due to logistic problems (“human errors”). Sixty-four cases were caused by the specimen not having been taken or having failed to reach the laboratory. Other reasons were misunderstandings in the responsibility for sampling, transfer to another hospital, or early discharge (⬍48 h) and omission of recommended early sampling. In all these cases the parents had wanted their baby to be tested and these children were screened subsequently. Screening was definitely refused by the parents of 163 children (0.1% of target population). Screening could be positively confirmed in 97.8% of the target population. There remained 2.0% of the target population (2,516 newborns) of which parents were contacted by regional public health offices due to missing screening notifications. They, however, did not respond, so that screening status of these newborns could not be checked. In the meanwhile the rate of nonresponders is continuously decreasing (data not shown). DISCUSSION
Although the importance of informed consent preceded by counseling is widely accepted in genetic screening, the practicability in the context of newborn screening has been doubted [19]. Lack of knowledge of genetic disorders has been considered to be a particular barrier to informed consent. Difficulties have also been seen in the fact that those giving consent, i.e., parents, may not be those who will be directly involved in the consequences of the test, i.e., the possibly affected child. On the other hand, newborn screening must be recognized as a “medical act” [17]. This implies the obligation to respect fundamental ethical principles, i.e., the aim being medical intervention for the benefit of the newborn tested but also the principles of consent, confidentiality, and counseling of the recipients (or in this case their parents) [15]. The recognition of newborn screening as a medical act is also important because it imposes limits on the degree of state intervention in the program since these fundamental principles must be respected [17]. Although in newborn screening truly informed consent is difficult to achieve [19], the Bavarian approach has been to inform parents as thoroughly as possible. A recently performed inquiry by questionnaire has shown very high acceptability of the program
within the medical community and confirmed the practicability of the procedures involved. It has already been reported that adequately informed parents have a strong positive attitude toward early detection of diseases through screening [16]. The Bavarian approach shows that obtaining written consent is indeed practicable in newborn screening. The comprehensive information strategy may have been instrumental. From January 1999 to September 2000 three newsletters were used to direct specific information to the senders of specimens and public health offices. These newsletters contained up-to-date data on the detected cases and on the development of regional and overall participation rates. In addition, the reports were used to deal with various issues recognized by the continuous process of monitoring and evaluating the system, e.g., awareness of the clinical relevance of early detection of “new” disorders, the benefits of demographic tracking in protecting newborns from procedural screening failures, and the importance of early sampling. Another factor is the implementation of effective process quality assurance measures. The system allows for continuously monitored coverage on a regional basis so that intensified measures of information and education can be directed to regions or individual birth units where weaknesses are detected. Individual measures (e.g., discussions with responsible health care workers and articles in local newspapers) were regularly taken when the regional statistical data or other evidence indicated local problems (e.g., noticeable refusal rates for data transmission or screening or delayed sampling time). One key element of the program is the tracking and counseling of parents of those newborns without screening notification. Another major advantage of this system is that procedural failures can be quickly corrected, allowing for still timely testing of initially unscreened children. Studies on screening failures leading to missed cases of disease have shown that infants who are never screened represent a serious problem in newborn screening, although their absolute number is low [20]. Our data on procedural failures underscore the call for the development of “fail-safe” mechanisms that can detect, prevent, or correct the usually underlying human errors. In this context it is important to note that in only a minority of untested children detected by demographic tracking in Bavaria was lack of screening due to refusal of the parents. Interestingly, the number of children not initially screened due to procedural problems (0.3% of the target population) is in good agreement with the figure extrapolated from missed cases of PKU and congenital hypothyroidism in various mandatory programs throughout the United Kingdom (0.25%) [16]. Definite refusal of screening accounted for only a few cases in Bavaria (163 newborns, corresponding to 0.1%
CONSENT IN NEWBORN SCREENING
of the target population). There is uncertainty regarding screening among children of nonresponders to parental contacts by the public health services (2.0% of the target population). This 2%, whose parents failed to respond to contact by their public health office, consists of three groups: (1) children screened outside the program, (2) children screened within the program whose parents refused data transmission to the screening center (their names could not be matched with the list of names from the screening center), and (3) truly unscreened children. These three groups cannot be distinguished. It is likely, however, that most of these were in group 2: parents who explicitly refused data transmission to the screening center are unlikely to be pleased about contacts related to an issue that they wanted to be left to their discretion. Those presumed few who had explicitly refused both data transmission and laboratory investigations would have missed screening, but were given a second chance for access to the program by the tracking procedure. In conclusion, the data show that the requirement for written consent does not prevent high compliance with newborn screening provided there is an appropriate strategy to disseminate information and surveillance by a tracking system. This encourages the obtainment of potential benefits of expanded MS–MSbased newborn screening in accordance with respect for individual rights.
5.
6.
7. 8.
9. 10. 11. 12.
13.
14.
15. 16.
REFERENCES 1. Chace DH, Millington DS, Terada N, Kahler SG, Roe CR, Hofman LF. Rapid diagnosis of phenylketonuria by a quantitative analysis for phenylalanine and tyrosine in neonatal blood spots by tandem mass spectrometry. Clin Chem 1993;39:66–71. 2. Chace DH, Sherwin JE, Hillman SL, Lorey F, Cunningham GC. Use of phenylalanine-to-tyrosine ratio determined by tandem mass spectrometry to improve newborn screening for phenylketonuria of early discharge specimens collected during the first 24 hours. Clin Chem 1998;44:2405–9. 3. Levy HL. Newborn screening by tandem mass spectrometry: a new era. Clin Chem 1998;44:2401–2. 4. Chace DH, Hillman SL, Millington DS, Kahler SG, Roe CR, Naylor EW. Rapid diagnosis of maple syrup urine disease in
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blood spots from newborns by tandem mass spectrometry. Clin Chem 1995;41:62–8. Chace DH, Hillman SL, Millington DS, Kahler SG, Adam BW, Levy HL. Rapid diagnosis of homocystinuria and other hypermethioninemias from newborns’ blood spots by tandem mass spectrometry. Clin Chem 1996;42:349–55. Clayton PT, Doig M, Ghafari S, Meaney C, Taylor C, Leonard JV, et al. Screening for medium-chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry. Arch Dis Child 1998;79:109–15. Barlett K, Pourfarzam M. Tandem mass-spectrometry—the potential. J Inherited Metab Dis 1999;22:568–71. Green A, Pollit RJ. Population newborn screening for inherited metabolic disease: current UK perspectives. J Inherited Metab Dis 1999;22:572–9. Wald NJ, Morris JK. Neonatal screening for cystic fibrosis. Br Med J 1998;316:404–5. Dodge JA. Cystic fibrosis should be added to diseases sought in all newborns. Br Med J 1998;317:411. Hall DM, Michel JM. Screening in infancy. Arch Dis Child 1995;72:93–6. Stone DH, Stewart S. Screening and the new genetics: a public health perspective on the ethical debate. J Public Health Med 1996;18:3–5. Faden R, Holtzman NA, Chwalow AJ. Parental rights, child welfare, and public health: the case of PKU screening. Am J Public Health 1982;72:1396–400. Holtzman NA, Faden R, Chwalow AJ, Horn SD. Effect of informed consent on mother’s knowledge of newborn screening. Pediatrics 1983;72:807–12. Edwards A. Neonatal screening: pretest counselling and informed consent should be prerequisites. Br Med J 1996;312:182–3. Pollit RJ, Green A, McCabe CJ, Booth A, Cooper NJ, Leonard JV, Nicholl J, Nicholson P, Tunaley JR, Virdi NK. Neonatal screening for inborn errors of metabolism: cost, yield and outcome. Health Technol Assess 1997;1:1–202. Knoppers BM, Laberge CM, editors. Genetic screening: from newborns to DNA typing. Amsterdam/New York/Tokyo/Singapore: Elsevier, 1990:379–90. Bavarian State Office for Statistics and Data Processing (Bayerisches Landesamt fu¨r Statistik und Datenverarbeitung), editor. Bayern-Daten. Available at http://www.bayern.de. Accessed January 29, 2001. Chadwick R, ten Have H, Husted J, Levitt M, McGleenan T, Shickle D, Wiesing U. Genetic screening and ethics: European perspectives. J Med Philos 1998;23:255–73. Holtzman C, Slazyk WE, Cordero JF, Hannon WH. Descriptive epidemiology of missed cases of phenylketonuria and congenital hypothyroidism. Pediatrics 1986;78:553–8.
Very High Compliance in an Expanded MS–MS-Based Newborn Screening Program despite Written Parental Consent Bernhard Liebl, M.D.,*,1 Uta Nennstiel-Ratzel, M.D., M.P.H.,* Ru¨diger von Kries, M.D.,† Ralph Fingerhut, Ph.D.,‡ Bernhard Olgemo¨ller, M.D., Ph.D.,‡ Andreas Zapf, M.D.,§ and Adelbert A. Roscher, M.D.¶ *Public Health Newborn Screening Center of the State of Bavaria, Landesuntersuchungsamt Su¨dbayern, D-85762 Oberschleissheim, Germany; †Institute for Social Pediatrics and Adolescent Medicine and ¶Children’s Hospital, University of Munich, Munich, Germany; ‡Labor Becker, Olgemo¨ller & Kollegen, Munich, Germany; and §Bavarian State Ministry of Health, Munich, Germany Published online December 20, 2001
Objectives. In Bavaria, Germany, an expanded MS– MS-based newborn screening program was implemented in 1999. The coverage of new additional conditions and novelty of technology required introduction of written parental consent. Here we evaluated the influence of the consent procedure on compliance by systematic demographic tracking. Methods. Comprehensive information was provided for parents, professionals, and the public. Screening notifications were matched with all birth notifications on name and date of birth. Parents of children without screening notification were contacted and counseled. Results. Between August 1, 1999, and July 31, 2000, 123,284 children eligible for screening were born. Of these, 116,652 were matched successfully. Among 6,632 parents contacted, 2,516 (2%) did not respond. Three thousand thirty-four children were screened but the parents initially refused to participate in tracking. Five hundred ninety-four were screened outside the program. Four hundred eighty-eight untested newborns were identified. Three hundred twenty-five screening failures due to logistic problems were tested subsequently. Screening was definitely refused by the parents of 163 children (0.1% of target population). Conclusions. With appropriate information provided and surveillance by tracking, high compliance with newborn screening can be achieved despite a written consent requirement. 䉷 2001 American Health Foundation and Elsevier Science (USA)
1
To whom correspondence and reprint requests should be addressed at the Public Health Newborn Screening Center of the State of Bavaria, Landesuntersuchungsamt Su¨dbayern, D-85762 Oberschleissheim, Germany. Fax: ⫹⫹49-89-31560-458. E-mail: [email protected].
Key Words: newborn screening; tandem mass spectrometry; consent; tracking.
INTRODUCTION
Tandem mass spectrometry (MS–MS) is a both promising and challenging new technology that has began to have significant impact in newborn screening. MS– MS is a highly sensitive and specific method to detect phenylketonuria (PKU). Compared with previously used diagnostic methods (e.g., bacterial inhibition assay, fluorometric assay) screening can be performed earlier and with lower false positive rates [1–3]. In addition to PKU, MS–MS allows one to screen for further disorders in the same analytical run without significant additional test costs. Among these are maple syrup urine disease (MSUD) [4], homocystinuria [5], and medium chain acyl-CoA dehydrogenase (MCAD) deficiency [6], as well as at least a dozen other disorders in amino, organic, and fatty acid metabolism [7]. Although very few of the diseases likely to be detected by MS–MS are regarded as completely untreatable, the long-term outcome in some of the more severe forms is dubious [8]. There are controversial views over screening for such diseases. One opinion is that early knowledge of a poorly or even untreatable serious disorder might cause more harm than good [9]. Another point of view is that under the provision of minor technical risk perfect treatment options are not a prerequisite as long as the affected newborn may benefit. Furthermore, parents usually want to be informed about the child’s problems as soon as possible [10,11]. It even can be argued that there is a “right” to information and that withholding information is an unjustifiable form of medical paternalism [12].
127
0091-7435/01 $35.00 䉷 2001 American Health Foundation and Elsevier Science (USA) All rights reserved.
128
LIEBL ET AL.
In this context the question of adequate pretest counseling and consent arises. There is disagreement in the ethical and legal literature as to whether parents should have the right to refuse “standard health care” that might benefit their child, e.g., screening for PKU [13–15]. On the other hand, they have a clear right to refuse screening that is being done primarily for the benefit of the family [16]. The traditional parental “informed refusal” approach may be acceptable for screening for some of the diseases detectable by MS–MS (e.g., PKU). However, when disorders for which evidence for effective treatability is incomplete are included, individualized informed consent must be obtained [17]. Unlike screening programs in other countries, in Germany screening has always been regarded as a medical act. Participation is voluntary, even for basic tests such as for PKU and congenital hypothyroidism (CH), though there has been no clear policy on the question of individual counseling and consent. In the state of Bavaria (120,000–130,000 births per annum) [18], a prospective MS–MS-based model program was implemented in 1999 following an intense medical, ethical, and legal debate. Adequate pretest information and written consent by the parents were required for participation in the program extended to screening for MSUD; homocystinuria; MCAD deficiency; glutaric acidemia type I; propionic, methylmalonic, and isovaleric acidemia; and other diseases investigated under research conditions. Non-MS–MS-based tests are used to screen for CH, congenital adrenal hyperplasia (CAH), biotinidase deficiency, and galactosemia. A comprehensive information strategy assisted by a demographic tracking system was introduced to ensure high quality of the entire screening process. The goal was to ensure equitable access and to attain the highest level of voluntary compliance possible. The aim of this study was to find out whether a high compliance with the screening program can be achieved despite the move to written parental consent. METHODS
Information Policy With the increasing number of diseases being covered by the screening program and the need for written consent, information strategy has become increasingly important. Policies were designed and approved by appropriate scientific, ethical, and legal committees. Detailed written information on the individual tests, interpretation of results, and the various disorders screened for is summarized in a screening manual for professionals. A leaflet for health care workers was designed as short information for all those taking specimens (physicians, midwives, nurses) and to assist pretest counseling. A parent information pamphlet and consent sheet provides additional written information about the aims
of the program, the test procedures applied, and the features and consequences of the defects that may be identified. Two forms of written parental consent were asked for independently: (1) for taking part in the laboratory investigations as a whole (expanded MS–MSbased screening as well as basic tests such as for PKU, CH, CAH, biotinidase deficiency and galactosemia) and (2) for transmission of personal data to the state screening center for the purpose of demographic tracking facilitating quality assurance of the entire screening process. Parents are given three alternatives to sign the consent form accompanying the information pamphlet: (1) consent to both the laboratory investigations and the data transmission from the laboratory to the public health services, (2) consent to only the laboratory investigations and not to data transmission, and (3) refusal of newborn screening. The form signed by one of the parents stays with the patient record held by the specimen submitter. The submitter marks the parents’ choice (alternative 1 or 2) on the screening card. A telephone inquiry service for all participants (health care workers and parents) has been established for assistance for all questions concerning the program. Through this central service senders of blood samples and attending physicians can also ask for screening results of children in their care. Program-specific education of medical personnel was simultaneously intensified by teaching at midwife and public health schools. Half-yearly newsletters reporting on the progress of the program, detection rates, and difficulties and problems are distributed to all participants. The public is regularly informed by interviews, reports, and official statements in the media (TV, radio, press). Demographic Tracking All procedures involved in this system were approved by the Bavarian data protection commissioner. The laboratory service, the state screening center, and the regional public health offices cooperate to ensure that the new expanded program is offered to every baby in Bavaria (Fig. 1). Those who do not wish to participate in this state-supported program can obtain newborn screening at some private laboratory services still offering less comprehensive programs. All demographic data of the children screened within the statesupported program are recorded electronically by the laboratory. In the case of parental consent to participate in tracking, these data are transmitted electronically to the state center. This center arranges the data according to place of residence and generates individual lists with names and dates of birth (no results) of tested newborns for each of the 76 regional public health offices covering the entire state territory (71,000 km2) [18]. The regional public health offices receive these
129
CONSENT IN NEWBORN SCREENING
FIG. 1. Demographic tracking. Scheme of information flow.
lists on a weekly basis and match them with the birth notifications in their region. In Bavaria, registration offices report birth notifications to public health offices in the areas of the newborns’ residences. This was already established before implementation of the newborn screening tracking system for the purpose of health consultation of families. The parents of children missing on the screening lists are contacted individually. The reasons may be (1) procedural failures (e.g., lost specimens), (2) refusal of data transmission, (3) screened outside the program, or (4) refusal of screening. If screening cannot be confirmed the parents are again specifically counseled on the importance of newborn screening. The personal data are extinguished immediately after matching, at the latest 6 weeks after receipt. On a monthly basis, the regional public health offices report anonymous statistical data on the results of follow-up to the state screening center. RESULTS
Between August 1, 1999, and July 31, 2000, 123,284 children eligible for screening were born (Table 1). Of these, 116,652 newborns were successfully matched on name and date of birth. Parents of 6,632 newborns had to be contacted by regional public health workers because the names of their children were missing on the
TABLE 1 Results of Demographic Tracking in Bavaria from August 1, 1999, to July 31, 2000
Notified births First 3 days deaths Target population Successfully matched (Names of screened newborns against birth notifications) Parental contact by regional public health offices (due to missing names on screening lists) Positive parental response to contact by regional public health office Results Screened Within model program, data transmission to state center refused Outside model program Untested “Human errors”: misunderstandings, lost samples, etc. (subsequently screened) Screening refused Screening confirmed No parental response to contact by regional public health office (screening status uncertain)
N
% of target population
123,490 206 123,284
100%
116,652
94.6%
6,632
5.4%
4,116
3.3%
3,034 594
2.5% 0.5%
325 163 120,605
0.3% 0.1% 97.8%
2,516
2.0%
130
LIEBL ET AL.
screening lists. In 4,116 cases (62% of parental contacts) the parents responded so that the reason for the names of their children missing on the screening lists could be clarified. There were 3,034 children who had been screened, but the parents had refused to identify to the screening center. Five hundred ninety-four children had been screened by other programs, mostly because of delivery outside the state of Bavaria. Four hundred eighty-eight untested newborns were identified. Missing screening in 325 of these (0.3% of the target population) was due to logistic problems (“human errors”). Sixty-four cases were caused by the specimen not having been taken or having failed to reach the laboratory. Other reasons were misunderstandings in the responsibility for sampling, transfer to another hospital, or early discharge (⬍48 h) and omission of recommended early sampling. In all these cases the parents had wanted their baby to be tested and these children were screened subsequently. Screening was definitely refused by the parents of 163 children (0.1% of target population). Screening could be positively confirmed in 97.8% of the target population. There remained 2.0% of the target population (2,516 newborns) of which parents were contacted by regional public health offices due to missing screening notifications. They, however, did not respond, so that screening status of these newborns could not be checked. In the meanwhile the rate of nonresponders is continuously decreasing (data not shown). DISCUSSION
Although the importance of informed consent preceded by counseling is widely accepted in genetic screening, the practicability in the context of newborn screening has been doubted [19]. Lack of knowledge of genetic disorders has been considered to be a particular barrier to informed consent. Difficulties have also been seen in the fact that those giving consent, i.e., parents, may not be those who will be directly involved in the consequences of the test, i.e., the possibly affected child. On the other hand, newborn screening must be recognized as a “medical act” [17]. This implies the obligation to respect fundamental ethical principles, i.e., the aim being medical intervention for the benefit of the newborn tested but also the principles of consent, confidentiality, and counseling of the recipients (or in this case their parents) [15]. The recognition of newborn screening as a medical act is also important because it imposes limits on the degree of state intervention in the program since these fundamental principles must be respected [17]. Although in newborn screening truly informed consent is difficult to achieve [19], the Bavarian approach has been to inform parents as thoroughly as possible. A recently performed inquiry by questionnaire has shown very high acceptability of the program
within the medical community and confirmed the practicability of the procedures involved. It has already been reported that adequately informed parents have a strong positive attitude toward early detection of diseases through screening [16]. The Bavarian approach shows that obtaining written consent is indeed practicable in newborn screening. The comprehensive information strategy may have been instrumental. From January 1999 to September 2000 three newsletters were used to direct specific information to the senders of specimens and public health offices. These newsletters contained up-to-date data on the detected cases and on the development of regional and overall participation rates. In addition, the reports were used to deal with various issues recognized by the continuous process of monitoring and evaluating the system, e.g., awareness of the clinical relevance of early detection of “new” disorders, the benefits of demographic tracking in protecting newborns from procedural screening failures, and the importance of early sampling. Another factor is the implementation of effective process quality assurance measures. The system allows for continuously monitored coverage on a regional basis so that intensified measures of information and education can be directed to regions or individual birth units where weaknesses are detected. Individual measures (e.g., discussions with responsible health care workers and articles in local newspapers) were regularly taken when the regional statistical data or other evidence indicated local problems (e.g., noticeable refusal rates for data transmission or screening or delayed sampling time). One key element of the program is the tracking and counseling of parents of those newborns without screening notification. Another major advantage of this system is that procedural failures can be quickly corrected, allowing for still timely testing of initially unscreened children. Studies on screening failures leading to missed cases of disease have shown that infants who are never screened represent a serious problem in newborn screening, although their absolute number is low [20]. Our data on procedural failures underscore the call for the development of “fail-safe” mechanisms that can detect, prevent, or correct the usually underlying human errors. In this context it is important to note that in only a minority of untested children detected by demographic tracking in Bavaria was lack of screening due to refusal of the parents. Interestingly, the number of children not initially screened due to procedural problems (0.3% of the target population) is in good agreement with the figure extrapolated from missed cases of PKU and congenital hypothyroidism in various mandatory programs throughout the United Kingdom (0.25%) [16]. Definite refusal of screening accounted for only a few cases in Bavaria (163 newborns, corresponding to 0.1%
CONSENT IN NEWBORN SCREENING
of the target population). There is uncertainty regarding screening among children of nonresponders to parental contacts by the public health services (2.0% of the target population). This 2%, whose parents failed to respond to contact by their public health office, consists of three groups: (1) children screened outside the program, (2) children screened within the program whose parents refused data transmission to the screening center (their names could not be matched with the list of names from the screening center), and (3) truly unscreened children. These three groups cannot be distinguished. It is likely, however, that most of these were in group 2: parents who explicitly refused data transmission to the screening center are unlikely to be pleased about contacts related to an issue that they wanted to be left to their discretion. Those presumed few who had explicitly refused both data transmission and laboratory investigations would have missed screening, but were given a second chance for access to the program by the tracking procedure. In conclusion, the data show that the requirement for written consent does not prevent high compliance with newborn screening provided there is an appropriate strategy to disseminate information and surveillance by a tracking system. This encourages the obtainment of potential benefits of expanded MS–MSbased newborn screening in accordance with respect for individual rights.
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