中国・日本・米国における医薬品副作用/有害事象報告

30P-pm400
130th Annual Meeting of Pharmaceutical Society of Japan (PSJ) (日本薬学会第130年会), Okayama, Japan, 30 March 2010, ver. 1.1, 5 April 2010
中国・日本・米国における医薬品副作用/有害事象報告システムの比較
(Comparison of Post-marketing ADR/AE Reporting systems in China, Japan and USA)
陳鋒 (CHEN,
1)2)
Feng) ,
草間真紀子 (KUSAMA,
2)
Makiko) ,
津谷喜一郎 (TSUTANI,
3)
Kiichiro)
(Information Center, State Food & Drug Administration (SFDA), Beijing, China)
2東大院薬・医薬品評価科学講座 (Laboratory of Pharmaceutical Regulatory Science (PRS), Graduate School of Pharmaceutical Sciences, The University of Tokyo)
3東大院薬・医薬政策学講座 (Department of Drug Policy and Management (DPM), Graduate School of Pharmaceutical Sciences, The University of Tokyo)
1中国国家食品薬品監督管理局信息中心
Objective
Methods
The aim of this study was to compare the Adverse Drug Reaction (ADR) /
Adverse Event (AE) reporting systems in China, Japan and USA, in terms of
policy, regulation, technology and application, and to propose several
potential improving points for each country’s reporting system.
Both regulatory and academic literatures regarding the policy, regulation, technology
and application of ADR/AE reporting systems in China, Japan and USA were collected,
including those from websites. Based on qualitative analyses, some critical aspects
concerning ADR/AE reporting system are compared and discussed.
Results
Table 1 Forms for ADR / AE Reporting in China, Japan and USA
China
Table 4 Comparison of ADR/AE reporting route
Japan
USA
[J-1] 医薬品安全性情報報告書
[J-2] 医療機器安全性情報報告書
[J-3] 医薬品副作用感染症症例報告書
[J-4] 医薬品副作用感染症症例票(国内.外国)
[J-5] 医療機器不具合感染症症例報告書
[J-6] 予防接種後副反応報告書
[J-7] 健康食品等に関する健康被害受付処理票
[C-1] 药品不良反应/事件报告表
[C-2] 可疑医疗器械不良事件报告表
[C-3] 医疗器械不良事件补充报告表
[U-1] Form FDA 3500: FDA Safety Information and
Adverse Event Reporting Program
[U-2] Form FDA 3500A
[U-3] Form VAERS-1(FDA) Vaccine Adverse Event
Reporting System
To Whom
Customers/patients
Healthcare professionals
Industry (Importer, Manufacturer, Distributor, etc.)
Health care professional, consumer
（医療従事者、消費者）
Industries
（企業（輸入業者、製造者、販売者））
FDA
MHLW or Industry
In User facility, medical device AE:
If Death: both FDA and Manufacturer;
If Serious injuries: Manufacturer or FDA
distributor
Regional Center
importer
Regional Center
manufacturer
Regional Center
Regional Center
National Center
–
–
National Center
–
–
–
FDA
In Japan, only the marketing
authorization holders (MAHs) are
required to report ADR/AEs to PMDA.
FDA
FDA
Mandatory
Voluntary
Mandatory
Mandatory
Mandatory
Drugs
[C-1]
[J-1]
[U-1]
[C-1]
[J-3] [J-4]
[U-2]
Biologics
[C-1]
[J-1]
[U-1]
[C-1]
[J-3] [J-4]
[U-2]
Medical Devices
[C-2]
[J-2]
[U-1]
[C-2] [C-3]
[J-5]
[U-2]
Combination Products
Not specified
Not specified
[U-1]
Not specified
Not specified
[U-2]
Customers/patients
Reporting
NA
Reporting
Vaccine
Not specified
[J-6]
[U-3]
Not specified
Not specified
[U-2]
Healthcare professionals
Initial assessing and reporting
Reporting
Reporting
Cosmetics
Not specified
[J-1]
[U-1]
Not specified
[J-3] [J-4]
[U-2]
[U-1]
Not specified
USA
Regional Center
Voluntary/Mandatory
[J-7]
Japan
–
Voluntary/
Mandatory
Not specified
China
Regional Center
China
Special nutritional
products
USA
USA
Country
Product Scope
Japan
Japan7)
FDA (If necessary, FDA will forward it to
manufacturer)
Table 2 Classification of the forms [Codes refer to Table 1]
Reporter
（報告者）
China
Not specified
Monitoring institution
Table 5 Comparison of the reporters’ roles
China
[U-2]
Industries
distributor
Initial assessing and reporting
importer
Initial assessing and reporting
manufacturer
Table 3 Comparison of ADR/AE reporting forms for drugs and biologics by healthcare professionals / patients
[C-1]
China
[J-1]
Japan
[U-1]
USA
Death (Cause and Time) （死亡）
Y
Y
Y
Life-threatening （死亡又は障害につながる）
Y
Y
Y
Hospitalization -initial or prolonged （入院／入院期間の延長）
Y
Y
Y
ITEM
Roles
Japan
Monitoring institution
Regional Center
National Center
Collecting, investigating, assessing and
reporting
Validating, analyzing, assessing,
reporting
Analyzing and assessing
In Japan, the marketing authorization
holders (MAHs) are responsible for
collecting, investigating, assessing and
reporting.
USA
Reporting
Reporting
Collecting, investigating, assessing and reporting
NA
NA
Analyzing and assessing
Analyzing and assessing
1. Report Scope （報告事項）
Serious
（重篤）
Adverse Event
（有害事象）
Disability or permanent damage （障害）
Y
Y
Y
Congenital anomaly/birth defect （後世代における先天性の疾病/異常）
Y
Y
Y
Other serious(Important Medical Events) （その他重篤）
N
Y
Y
Y
Y
N
Product problem (e.g., defects / malfunctions) （製品問題 例：欠陥／故障）
N
Y
Y
Product Use Error (medication error, or possible leading to medication error) （製品使用エラー）
N
N
Y
Problem with different Manufacturer of Same Medicine （異なる製造業者で同一の医薬品の問題）
N
N
Y
Name
Initials
Initials
Y
N
N
Y
N
N
Age at time of Event or Date of Birth （事象発生における年齢・生年月日）
Y
Y
Y
Sex（性別）
Y
Y
Y
Weight（体重）
Y
Y
Y
Race/ethnicity （人種・民族）
Y
N
Y
Other Relevant History: allergies, smoking, alcohol use, drug abuse, Radioactive treatment（治療歴・体質・嗜好）
N
Y
Y
ADR/AE history for patient’s family members （有害事象・副作用の家族歴）
Y
N
N
Before ADR/AE, whether accepted these treatments, such as radioactive, blood transfusion, medical operation,
and narcotherapy （有害事象・副作用発現前の措置・治療（放射線、輸血、手術、麻酔、など））
N
Y
N
Non-serious （非重篤）
Table 6 Comparison of timeframe for initial ADR/AE reporting
Scope
1. Death
Adverse Event
2. Patient Information （患者情報）
Patient- identifier （患者識別）
Contact Information
Medical record #
（患者連絡先）
（カルテ番号）
3. Event Description （有害事象について）
Date of Event （事象発生日）
Y
Y
Y
Date of Report （事象報告日）
Y
Y
Y
China
Serious
2. Life-threatening
3. Hospitalization -initial or
prolonged
4. Disability or permanent
damage
5. Congenital anomaly/birth
defect
6. Required intervention to
Prevent Permanent
impairment/damage devices
7. Other serious (Important
Medical Events)
Non-serious Unexpected
Expected
Product Problem
Product Use Error (medication error, or possible leading to
medication error)
Problem with different Manufacturer of Same Medicine
Drugs: Immediately
Medical devices: 5 days
15 days
Japan
15 days
15days: Unknown AE or all serious
events resulted from infections
and drugs with new active
ingredients within 2 years from
the date of approval .
30days: Known serious AE
NA
NA
Periodical
NA
NA
NA
NA
NA
Periodical
USA
5days: When need remedial action to
prevent substantial harm due to
suspect medical devices (MD).
7days: When the blood collection or
transfusion fatalities are concerned.
10days: When death or serious harm
happened in user facilities due to
suspect medical devices.
15days: When serious and unexpected
adverse events happened due to
suspect drug and biologic, including
human cell, tissue, and cellular and
tissue-based product.
30days: When possible death or serious
harm would happen due to suspect
MD.
NA
15 days
15 days (only for healthcare professionals and
consumers)
Discussions
• A uniformed form for different health related products used in USA may be convenient to reporters and may streamline
causality assessment between the adverse events and suspect products.
• Sweden (1978), USA (1993), China (1999), Australia (2003), Netherlands (2003), Canada (2003), Denmark (2003) and UK
(2005) have already begun to accept ADR reports from consumers, which have been playing increasingly significant roles
in post marketing surveillance8) 9) .
Consequence of
ADR/AE （副作用等の転帰）
Death, Recovered, Recovering, Treated and recovered, Complication （死亡、回復、など）
Y
Y
Y
Influence on fetus or causing fetus death （胎児に影響有、胎児死亡）
N
Y
N
Report type （種類）
Unlabelled, known （既知、未知）
Y
N
N
Signs and symptoms （症状）
Y
Y
Y
Medical status prior to the event （有害事象発生前の状態）
Y
Y
Y
Clinical course （経過）
Y
Y
Y
Treatment and outcome （処置と結果）
Y
Y
Y
Event abated after stopped or dose reduced of the suspect products? (Dechallenge) （被疑薬投与中止後の症状）
Y
N
Y
Event reappeared after reintroduction of the respect products? (Rechallenge) （被疑薬投与再開後の再発状況）
Y
Y
Y
Relevant tests/laboratory data, including dates （臨床検査値の記載）
Y
Y
Y
Name （名称）
Y
Y
Y
Strength （規格）
Y
Y
Y
• It is worth considering to launch a pilot project to allow consumers to report ADR/AE directly in Japan.
Manufacturer （製造者）
Y
Y
Y
Lot # （ロット番号）
Y
N
Y
• China is supposed to accelerate adaptation process of Chinese ICSRs to ICH E2B format.
Diagnosis or reason for use （診断・使用理由）
Y
Y
Y
Dose or Amount, Frequency （使用量、頻度）
Y
Y
Y
Dates of use （使用期間）
Y
Y
Y
Route of administration （投与経路）
Y
Y
Y
Expiration date （使用期限）
N
N
Y
NDC(national drug code) number or Unique ID （医薬品コード）
N
N
Y
Product name （名称）
Y
Y
Y
Therapy dates （治療日）
Y
N
Y
Strength （規格）
Y
N
N
Manufacturer （製造者）
Y
N
N
Lot #
Y
N
N
Y
N
N
only
only
both
6. Evaluation to AE （有害事象の評価）
Y
N
N
7. Product availability (Product available for evaluation) （評価のために報告先が製品を入手することは可能か否か）
N
N
Y
Description of ADE
（有害事象の記載方法）
4. Suspect Medicine Products （被疑薬・機器）
5. Concomitant medical products（併用薬・機器）
（ロット番号）
Diagnosis or reason for use （診断・使用理由）
Product scope includes only drug or only medical device, or both（併用薬/医療機器のみ記載か、不問か）
8. Also reported to （他組織への報告）
Manufacturer, user facility, distributor/importer （製造者、使用施設、販売者、輸入者）
Y
Y
Y
• China and UMC (Uppsala Monitoring Center, http://www.who-umc.org/) have decided in 2008 to collaborate with
adaptation Chinese Individual Case Safety Reports (ICSRs) to the international E2B format, which includes detailed
analysis regarding the ADR terminology and representation of Chinese drug names10 ).
• Some studies showed that positive and timely feedback to reporters would greatly encourage their reporting11).
Conclusions
• China and Japan could consider consolidating their separate ADR/AE reporting forms into one uniformed form, and
providing a single point of entry for all reporters.
• All 3 countries are recommended to build timely feedback mechanism to reporters.
References
1.
2.
3.
4.
日本公定書協会（編）. PMSの概要とノウハウ―製造販売後安全管理・調査担当者必携. 東京: じほう, 2008. p. 6-20.
Kessler DA. Introducing MEDWatch: A New Approach to Reporting Medication and Device Adverse Effects and Product Problems. JAMA. 1993;269(21):2765-8.
FDA. A MEDWatch Continuing Education Article, 1996. http://www.fda.gov/downloads /Safety/MedWatch /UCM168505.pdf (accessed on 18 November 2009)
FDA. Instructions for Completing Form FDA 3500.
http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/ucm149236.htm (accessed on 18 November 2009)
5. PMDA. 医療機関等からの医薬品又は医療機器についての副作用、感染症及び不具合報告の実施要領の改訂について. 6 July 2005.
http://www.info.pmda.go.jp/info/file/iryoukikan20050706.pdf (accessed on 16 December 2009)
6. SFDA. Provision for Monitoring and Management of Adverse Drug Reaction Reporting (SFDA Decree No.7), State Food & Drug Administration of China, 4 March 2004.
http://www.sfda.gov.cn/WS01/CL0053/24477.html (accessed on 18 December 2009)
7. PMDA. 医薬品の添付文書改訂業務に至る標準的な作業の流れについて. 10 February 2010.
http://www.info.pmda.go.jp/iyaku/file/h220210-001.pdf (accessed on 19 March 2010)
8. Blenkinsopp A, Wilkie P, Wang M, et al. Patient reporting of suspected adverse drug reactions: a review of published literature and international experience. Br J Clin Pharmacol.
2006; 63: 148-56.
9. Aagaard L, Nielsen LH, Hansen EH. Consumer reporting of adverse drug reactions: A retrospective analysis of the Danish adverse drug reaction database from 2004 to 2006.
Drug Saf. 2009; 32 (11): 1067-74.
10. Olsson S. Making Chinese ADR data available to the world. Uppsala Reports 2008; 43: 10.
11. Susanna M. et al. Reporting of adverse drug reactions may be influenced by feedback to the reporting doctor. Eur J Clin Pharmacol. 2007; 63: 505–8.
Acknowledgements
The authors sincerely appreciate the valuable comments from Dr. ONO, Shunsuke (Associate Professor) and Mr. YAMADA, Toru (PhD candidate)
and other members of the Laboratory of Pharmaceutical Regulatory Science (PRS), Faculty of Pharmaceutical Sciences, The University of Tokyo.