E2B(R) CLINICAL SAFETY DATA MANAGEMENT: 

DATA ELEMENTS FOR TRANSMISSION OF 

INDIVIDUAL CASE SAFETY REPORTS 

Revision 2 

This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current 

thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 

bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of 

the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA 

staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call 

the appropriate number listed on the title page of this guidance. 

For questions regarding this draft document contact (CDER) Roger Goetsch 301-770-9299, or 

(CBER) Lise Stevens-Hawkins 301-827-6085. 
INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS 

FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE 

ICH HARMONISED TRIPARTITE GUIDELINE 

REVISION OF THE ICH GUIDELINE ON 

CLINICAL SAFETY DATA MANAGEMENT: 

DATA ELEMENTS FOR TRANSMISSION OF 

INDIVIDUAL CASE SAFETY REPORTS 

E2B(R) 

Version 2.0 

12 May 2005 

Recommended for Adoption 

at Step 2 of the ICH Process 

on 12 May 2005 

by the ICH Steering Committee 

This Guideline has been developed by the appropriate ICH Expert Working Group E2B(R) and is subject 

to consultation by the regulatory parties, in accordance with the ICH Process 
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1 

2 E2B (R) 

3 REVISION OF THE ICH GUIDELINE ON 

4 CLINICAL SAFETY DATA MANAGEMENT: 

5 

6 DATA ELEMENTS FOR TRANSMISSION OF 

7 INDIVIDUAL CASE SAFETY REPORTS 

8 

9 

10 TABLE OF CONTENTS 

11 

12 

13 PREAMBLE........................................................................................................... 

14 

15 1. INTRODUCTION................................................................................................ 

16 1.1 Scope of this guideline ....................................................................................... 

17 1.2 Background ........................................................................................................ 

18 1.3 Notes on format of this document ...................................................................... 

19 1.4 Definition of data elements ................................................................................ 

20 1.5 Minimum information ........................................................................................ 

21 1.6 General principles........................................................................ 

22 

23 2. GUIDELINE: CONTENT OF THE DATA ELEMENTS .............................. 

24 

25 A. Administrative and Identification Information................................................ 

26 A.1 Identification of the case safety report ............................................................... 

27 A.2 Primary source(s) of information ....................................................................... 

28 A.3 Information on sender and receiver of case safety report.................................... 

29 

30 B. Information on the Case .................................................................................... 

31 B.1 Patient characteristics.......................................................................................... 

32 B.2 Reaction(s)/event(s)........................................................................................... 

33 B.3 Results of tests and procedures relevant to the investigation of the patient ....... 

34 B.4 Drug(s) information ........................................................................................... 

35 B.5 Narrative case summary and further information .............................................. 

36 

37 3. GLOSSARY......................................................................................................... 

38 

39 ATTACHMENTS: 

40 

41 1. Definition of Interval List.. .............................................................. 

42 2. Examples .............................................................................................................
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43 E2B(R) 

44 REVISION OF THE ICH GUIDELINE ON 

45 CLINICAL SAFETY DATA MANAGEMENT : 

46 

47 DATA ELEMENTS FOR TRANSMISSION OF 

48 INDIVIDUAL CASE SAFETY REPORTS 

49 

50 PREAMBLE 

51 This guideline provides additional information and clarification as well as some modifications to the ICH 

52 E2B guideline signed off on July 17, 1997 and modified as E2B(M) guideline in November 2000. It 

53 incorporates adjustments based on the experience gained after the implementation of the guideline in the 

54 three regions. It is recommended that the reader reviews this document as well as the companion 

55 document M2 ICSR Message Specification. 

56 

57 1. INTRODUCTION 

58 

59 1.1 Scope of this guideline 

60 The objectives of the working group are to standardize the data elements for transmission of individual 

61 case safety reports by identifying and where necessary or advisable within a particular region, by defining 

62 the data elements for the transmission of all types of individual case safety reports, regardless of source 

63 and destination. This guideline includes data elements of case safety reports for both pre and post approval 

64 periods and covers both adverse drug reaction and adverse event reports. It is not intended that this format 

65 should be used for cases in the integrated safety summary of a marketing license application dossier. For 

66 adverse reactions encountered in clinical trials, this format should be used only for those subject to 

67 expedited reporting. The scope of this topic does not encompass the definition of database structures, the 

68 design of a paper report form, quality control/quality assurance aspects, or technical security issues.

69 

70 1.2 Background 

71 Because of national and international agreements, rules, and regulations, individual case safety reports of 

72 adverse drug reactions and adverse events should be transmitted 

73 − from identified reporting sources to regulatory authorities and pharmaceutical companies; 

74 − between regulatory authorities; 

75 − between pharmaceutical companies and regulatory authorities; 

76 − within authorities or pharmaceutical companies; 

77 − from clinical investigators, via the sponsor, to ethics committees; 

78 − from authorities to the World Health Organization (WHO) Collaborating Center for International Drug 

79 Monitoring. 

80 

81 The transmission of such individual case safety reports relies on paper-based formats (e.g., yellow cards, 

82 CIOMS I forms, MedWatch) or electronic media usually by on-line access, tape or file transfer.

83 Considering the large number of potential participants in a world-wide exchange of information, there 

84 should be an electronic format capable of accommodating direct database to database transmission using 

85 message transfers. Successful electronic transmission of information relies on the definition of common 

86 data elements, provided in this document, and standard transmission procedures to be determined by the 

87 ICH Electronic Standards for the Transfer of Regulatory Information (ESTRI) Expert Working Group 

88 (M2). 

89 

90 1.3 Notes on format of this document 

91 Section 2 and its subsections designated A and B contain notes that are directed toward clarifying the 

92 nature of the data that should be provided. In addition, there are notes to assist in defining the format that 

93 should be used to transmit the data. In order to distinguish between these notes, the format is presented in 
E2B(R) Electronic Transmission of Individual Case Safety Reports 

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94 standard type of a slightly smaller font. 

95 

96 If a data element has a limited set of choices, the options are presented in bold Italic type. 

97 The standard allows for this information to be transmitted in encoded format. 

98 

99 1.4 Definition of data elements 

100 The format for individual case safety reports includes provisions for transmitting all the relevant data 

101 elements useful to assess an individual adverse drug reaction or adverse event report. The data elements 

102 are sufficiently comprehensive to cover complex reports from most sources, different data sets, and 

103 transmission situations or requirements; therefore, information for each and every data element will not be 

104 available for every transmission. In many, if not most instances, a substantial number of the data elements 

105 will not be known and therefore not included in the transmission. Where it was deemed important, 

106 provisions for unknown/not applicable were included (e.g., outcome, route of administration). However, 

107 since the transmission is intended to be electronic, it was thought to be unnecessary to include provisions 

108 to assign values of unknown for all data elements. Different ways of including the same data have been 

109 provided to cope with differing information contents: e.g., age information can be sent as date of birth and 

110 date of reaction/event, age at the time of reaction/event, or patient age group according to the available 

111 information (see section B.1.2 and the respective user guidance). In this example, age should be provided 

112 by the most precise available data element rather than including multiple elements of redundant data. 

113 Structured data are strongly recommended in electronic transmission and provisions for including 

114 information in this way have been made. However, structuring of the data also implies the use of 

115 controlled vocabularies, which are not yet available for some data elements. Electronic transmission of 

116 individual case safety reports should be implemented with MedDRA and the ICH M5 data elements and 

117 standards where applicable. The version number of MedDRA for the ICSR should be provided in the new 

118 field A.1.0.2 and as indicated in the companion document. MedDRA terms and ICH M5 related 

119 standards should be provided as codes. 

120 

121 In certain instances, there are provisions for the transmission of some free text items, including a full text 

122 case summary narrative. The transmission of other unstructured data, such as full clinical records or 

123 images is outside the scope of this guideline. However technical recommendations are made in the 

124 companion document. 

125 

126 1.5 Minimum information 

127 The minimum information for the transmission of a report should include at least one identifiable patient 

128 (section B.1), one identifiable reporter (section A.2), one reaction/event (section B.2), and one suspect 

129 drug with exceptions as described in user guidance of the section B.4. Because it is often difficult to 

130 obtain all the information, any one of several data elements is considered sufficient to define an 

131 identifiable patient (e.g., initials, age, sex) or an identifiable reporter (e.g., initials, address, qualification). 

132 It is also recognized that the patient and the reporter can be the same individual and still fulfill the 

133 minimum reporting criteria. Due to data privacy legislation in some countries the patient’s initials cannot 

134 be exchanged between countries. However, field B.1.1 may still be populated and user guidance for this 

135 field is provided. 

136 

137 In addition, to properly process the report, the following administrative information should be provided: 

138 the sender’s (case) safety report unique identifier (A.1.0.1), the date of the most recent information 

139 (A.1.7), the worldwide unique case identification number (A.1.10), the sender identifier (A.3.1.2), whether 

140 this case fulfills the local criteria for an expedited report (A.1.9), the type of report (A.1.4) and in the case 

141 of a “Report from study” the study type in which the reaction(s)/event(s) were observed (A.2.3.3).

142 

143 1.6 General Principles 
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144 The complete information available for a case should be provided in each ICSR. This applies to all types 

145 of ICSRs, i.e., reports with initial information on the case, follow-up information, and cases highlighted 

146 for nullification. The information available should be reported in a fully structured format using the 

147 relevant E2B(R) data elements and the applicable standard terminology. Text fields are intended only for 

148 additional information, which could not be provided in structured format using a reference standard 

149 terminology. However, a case narrative, i.e., a description of the case, should be provided (section B.5). 

150 For international transmissions, English is the generally accepted language.

151 

152 2. GUIDELINE: CONTENT OF THE DATA ELEMENTS 

153 The message content contains header information followed by E2B Data Elements. See the M2 ICSR 

154 Message Specification for information about the header. 

155 

156 The data elements are divided into sections pertaining to: 

157 A: Administrative and Identification Information 

158 A.1 - Identification of the case safety report 

159 A.2 - Primary source(s) of information 

160 A.3 - Information on sender and receiver of case safety report 

161 B: Information on the Case: 

162 B.1 - Patient characteristics 

163 B.2 - Reaction(s)/event(s) 

164 B.3 - Results of tests and procedures relevant to the investigation of the patient 

165 B.4 - Drug(s) information 

166 B.5 - Narrative case summary and further information

167 

168 

169 A. ADMINISTRATIVE AND IDENTIFICATION INFORMATION 

170 

171 A.1 Identification of the case safety report 

172 

173 A.1.0.1 Sender’s (case) safety report unique identifier 

174 User Guidance: 

175 

176 This identifier should remain constant in subsequent transmissions of the case by the same sender. Retransmitters 

177 should replace this value with their own unique identifier. The value should be a concatenation of “country code178 company or regulator name-report number”. Country code is the country of the primary source of the report (A.1.1). 

179 The company or regulator name is an internationally unique abbreviation or code for the sender’s organisation. The 

180 report number is the organisation’s international case number. Each component is separated from the other by a hyphen. 

181 For example, a report transmitted by a company to a regulatory authority concerning a case from France would populate 

182 A.1.0.1 with “FR-companyname-12345” where 12345 is a company’s unique case report number.

183 

184 In the case of an organisational change, (e.g., a merger between companies or a name change), follow up reports should 

185 be identified in A.1.0.1 by the identifier of the newly named organisation. However, the worldwide unique case 

186 identifier number (A.1.10) used in previous transmissions of the case should remain the same (see below). 

187 

188 A.1.0.2 MedDRA version used in this case safety report 

189 User Guidance: 

190 

191 See the companion document for appropriate format of the version. Only one version of MedDRA should be used to 

192 code all the relevant data elements. The version that should be used is always the last one released by the maintenance 

193 organisation. 

194 

195 A.1.1 Identification of the country of the primary source 

196 User Guidance: 

197 

198 Generally, this item would be the only country provided. This country should be that of the reporter (see Glossary). Provisions 

199 have been made to include other countries for unusual cases concerning foreign travel and sources of manufactured material 
E2B(R) Electronic Transmission of Individual Case Safety Reports 

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200 (A.1.2 and B.4.k.2.3). For example a patient living in country A experienced headache while traveling in country B; this headache 

201 was suspected to be an adverse drug reaction and was reported by a healthcare professional in country C. This field should be 

202 populated with the code of country C. See the companion document for appropriate country codes. 

203 

204 A.1.2 Identification of the country where the reaction/event occurred 

205 User Guidance: 

206 

207 This should be the country where the reaction occurred (i.e., the reaction occurred while the patient was traveling, but the report 

208 was made by a health professional on the patient’s return). In the example provided in the paragraph above, this field should be 

209 populated with the code of country B, the country in which the traveler experienced the reaction. 

210 

211 A.1.3 Date of this transmission 

212 User Guidance: 

213 

214 A full precision date should be used (i.e., day, month, year) 

215 

216 A.1.4 Type of report 

217 - Spontaneous report 

218 - Report from study 

219 - Other 

220 - Not available to sender (unknown) 

221 User Guidance: 

222 

223 A separate category for the designation of a literature source is covered in item A.2.2 and is not duplicated in this section which is 

224 intended to capture the type of report. If the case in the literature arises from spontaneous observations, “type of report” should be 

225 Spontaneous report. If the case arises from a study, “type of report” should be Report from study and the field A.2.3.3 should be 

226 populated with the appropriate value (see the User Guidance for that field). If it is unclear from the literature report whether or not 

227 the case(s) cited are spontaneous observations or whether they arise from a study, then this item should be Other. 

228 

229 Differentiation between types of studies (e.g. clinical trials or others should be given in section A.2.3.3). 

230 

231 The Not available to sender option allows for the transmission of information by a secondary sender (e.g., regulatory authority) 

232 where the initial sender did not specify the type of report; it differs from Other, which indicates that the sender knows the type of 

233 report but cannot fit it into the categories provided. 

234 

235 A.1.5 Seriousness 

236 User Guidance: 

237 

238 It is assumed that case seriousness is assessed by the reporter, otherwise it should be assessed by the sender. 

239 

240 A.1.5.1 Serious 

241 -Yes/no 

242 

243 A.1.5.2 Seriousness criteria (more than one can be chosen) 

244 - Results in death 

245 - Is life-threatening 

246 - Requires inpatient hospitalization or prolongation of existing hospitalization 

247 - Results in persistent or significant disability/incapacity (as per reporter's opinion) 

248 - Is a congenital anomaly/birth defect 

249 - Other medically important condition 

250 User Guidance: 

251 

252 The terms life-threatening and other medically important condition are defined in the ICH E2A and E2D guidelines. 

253 All the criteria apply to the case as a whole and should not be confused with the outcome(s) of individual 

254 reactions(s)/event(s) that are provided in section B.2.i.6. In addition section B.2.i.2.2 can be used to identify the 

255 seriousness criteria of each reaction/event in accordance with the user guidance for that section. 

256 

257 A.1.6 Date report was first received from source 
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258 User Guidance: 

259 

260 For senders dealing with initial information, this should be the date the information was received from the primary source. When 

261 retransmitting information received from another regulatory agency or another company or any other secondary source, A.1.6 

262 should be the date the retransmitter first received the information. 

263 

264 A full precision date should be used (i.e., day, month, year). 

265 

266 A.1.7 Date of the most recent information for this case 

267 User Guidance: 

268 

269 This date should be changed each time follow up information is received by the sender. However if the case is amended for any 

270 other reason (e.g., internal review by the sender or expert opinion) this date should not be changed but the field A.1.13 should be 

271 populated with the value “amendment” indicating that the case was amended by the sender. (See the User Guidance for the field 

272 A.1.13) 

273 

274 Because reports are sent at different times to multiple receivers, the initial/follow up status is dependent upon the receiver. For 

275 this reason an item to capture follow-up status is not included. However, the date of receipt of the most recent information taken 

276 together with the “sender identifier” (A.3.2) and “sender’s (case) report unique identifier” (A.1.0.1) provide a mechanism for each 

277 receiver to identify whether the report being transmitted is an initial or follow-up report. For this reason these items are considered 

278 critical for each transmission. 

279 A full precision date should be used (i.e., day, month, year). 

280 

281 A.1.8 Additional available documents held by sender 

282 

283 A.1.8.1 Are additional documents available? 

284 -yes/no 

285 

286 A.1.8.2 List of documents held by sender 

287 User Guidance: 

288 

289 The documents received from the primary source (e.g., clinical records, hospital records, autopsy reports) should be 

290 listed. It is recognized that these documents might not be obtainable in many instances. 

291 

292 A.1.9 Does this case fulfill the local criteria for an expedited report? 

293 - yes/no 

294 

295 User Guidance: 

296 

297 The definition of expedited is dependent upon the local regulatory requirements. This item should be used by the sender to 

298 indicate whether the case fulfills the local expedited requirements. When the countries of origin and destination of the 

299 transmission differ, the receiver should be aware that the information might not be applicable to the receiver’s country’s 

300 regulatory requirements. 

301 

302 A.1.10 Worldwide unique case identification number. 

303 User Guidance: 

304 

305 Only A.1.10.1 or A.1.10.2 should be used. No case should have more than one of these items completed. The contents of 

306 whichever item is used should remain unchanged for any transmissions subsequent to the original transmission. 

307 When a regulator is the initial sender, A.1.10.1 should be used. 

308 When an entity other than a regulator is the initial sender, A.1.10.2 should be used. When a sender has not previously received a 

309 valid E2B/M2 report electronically, the identifiers (content and format) in A.1.0.1 and A.1.10.1 or A.1.10.2 should be identical. 

310 Retransmitters should use their own sender’s (case) safety report unique identifier (A.1.0.1), but not change A.1.10.1 or A.1.10.2. 

311 See examples in attachment 2. 

312 

313 A.1.10.1 Regulatory authority’s case report number 

314 

315 A.1.10.2 Other sender’s case report number 

316 
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317 A.1.11 Other case identifiers in previous transmissions 

318 -yes 

319 User Guidance: 

320 

321 This item should be completed only if the answer is yes. 

322 

323 A.1.11.1 Source(s) of the case identifier (e.g., name of the company, name of regulatory 

324 agency) (repeat as necessary)

325 User Guidance: 

326 

327 This repeatable item should be used in conjunction with A.1.11.2 to provide all other case identifiers electronically 

328 transmitted, perhaps by multiple other senders. If the case has been received from another sender all other case 

329 identifiers included in A.1.11.1 and A.1.11.2 should be present. In addition the identifier of the previous sender 

330 (A.1.0.1) should be included here by the retransmitter. See examples in attachment 2 

331 

332 A.1.11.2 Case identifier(s) 

333 

334 A.1.12 Identification number of the report which is linked to this report (repeat as necessary)

335 User Guidance: 

336 

337 This section should be used to identify reports or cases that warrant being evaluated together. This includes, but is not limited to, a 

338 mother-child pair where both had reactions/events, siblings with common exposure, several reports involving the same patient 

339 (e.g., a report sent via paper without a valid E2B/M2 electronic report identifier), several similar reports from same reporter

340 (cluster). The reason for the linkage between ICSRs should be provided in B.5.4. See examples in attachment 2. 

341 

342 A.1.13 Report nullification / amendment 

343 - nullification 

344 - amendment 

345 User Guidance: 

346 

347 This item should be used to indicate that a previously transmitted report is either considered completely void (nullified), (for 

348 example when the whole case was found to be erroneous), or amended, (for example when after an internal review or according to 

349 an expert opinion some items have been modified such as adverse event terms, seriousness, seriousness criteria or causality 

350 assessment). It is important to use the same case report number previously submitted. The date originally reported in A.1.7 

351 should not be changed in an amended report. 

352 

353 A.1.13.1 Reason for nullification / amendment (free text)

354 

355 A.1.14 Was the case medically confirmed, if not initially from a health professional? 

356 - yes/no 

357 User Guidance: 

358 

359 This section should be completed if the primary source of information was a lawyer, consumer, or other non-health professional.

360 It is important because of regional differences in regulations concerning lay reports. 

361 

362 A.2 Primary source(s) of information 

363 The primary source(s) of the information is the person who reports the facts. This should be distinguished 

364 from senders (secondary sources) who are transmitting the information, (e.g., industry to regulatory 

365 authority).

366 Any or all of the three subsections (A.2.1, A.2.2, A.2.3) can be used. In the case of a published study or 

367 published individual case, the reporter would be the investigator or first author, and details on publication 

368 and trial type should also be provided. 

369 

370 A.2.1 Primary source(s) (repeat as necessary) 

371 

372 A.2.1.1 Reporter identifier (name or initials) 

373 User Guidance: 
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374 

375 The identification of the reporter could be prohibited by certain national confidentiality laws or directives. The 

376 information should be provided when it is in conformance with the regional confidentiality requirements. In any case, at 

377 least one subsection should be completed to ensure there is an identifiable reporter. If only the name of the reporter is 

378 known and providing this name is prohibited because of confidentiality requirements, initials can be used. 

379 

380 A.2.1.2 Reporter’s address 

381 User Guidance: 

382 

383 See the companion document for format specifications. 

384 

385 A.2.1.3 Country 

386 User Guidance: 

387 

388 See the companion document for format specifications. 

389 

390 A.2.1.4 Qualification 

391 − Physician 

392 − Pharmacist 

393 − Other health professional 

394 − Lawyer 

395 − Consumer or other non health professional

396 User Guidance: 

397 

398 In some regions, consumer and lawyer reports should be transmitted only when there is medical confirmation. 

399 

400 A.2.2 Literature reference(s) 

401 User Guidance: 

402 

403 References should be provided in the Vancouver Convention (known as "Vancouver style") as developed by the International 

404 Committee of Medical Journal Editors. The standard format, as well as formats for special situations can be found in the 

405 following reference which is in the Vancouver style. International Committee of Medical Journal Editors. Uniform requirements 

406 for manuscripts submitted to biomedical journals. N Engl J Med 1997; 336:309-15. 

407 

408 A.2.3 Study identification 

409 

410 A.2.3.0 Study registration number 

411 User Guidance 

412 

413 This field should be populated with the study registration number if applicable. 

414 

415 A.2.3.1 Study name 

416 User Guidance: 

417 

418 This field should be populated by the study name as approved by the regulator in each region. 

419 

420 A.2.3.2 Sponsor study number 

421 User Guidance: 

422 

423 This section should be completed only if the sender is the study sponsor or has been informed of the study number by 

424 the sponsor. 

425 

426 A.2.3.3 Study type in which the reaction(s)/event(s) were observed 

427 − Clinical trials 

428 − Individual patient use (e.g.,”compassionate use” or named patient basis)

429 − Other studies (e.g., pharmacoepidemiology, pharmacoeconomics, intensive monitoring)

430 User Guidance: 

431 
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432 This information should be provided if the field A.1.4 Type of report has been populated with “Report from study”. 

433 

434 A.3 Information on sender of case safety report 

435 

436 A.3.1 Type 

437 − Pharmaceutical company 

438 − Regulatory authority 

439 − Health professional 

440 − Regional pharmacovigilance center 

441 − WHO collaborating center for international drug monitoring 

442 − Other (e.g. distributor, study sponsor, or contract research organization)

443 User Guidance: 

444 

445 In this context, a pharmaceutical company includes biotechnology companies and other manufacturers required to 

446 submit individual case safety reports. 

447 

448 A.3.2 Sender identifier 

449 User Guidance: 

450 

451 Identifies the sender, (e.g., company name or regulatory authority name). It is important that this item should be completed. 

452 

453 A.3.3 Person responsible for sending the report 

454 User Guidance: 

455 

456 The name of person in the company or agency who is responsible for the authorization of report dissemination. This would 

457 usually be the same person who signs the covering memo for paper submissions. The inclusion of the name of this person in the 

458 transmission could be subject to national or international regulations. 

459 

460 A.3.4 Sender’s address, fax, telephone and E-mail address 

461 

462 B. INFORMATION ON THE CASE 

463 

464 B.1 Patient characteristics 

465 User Guidance: 

466 

467 This section applies to the subject who experienced one or several adverse reactions/events. 

468 In cases where a fetus or nursing infant is exposed to one or several drugs through the parent and experience one or several 

469 adverse reactions/events, information on both the parent and the child/fetus should be provided. Reports of these cases are 

470 referred to as parent-child/fetus reports. The following general principles should be used for filing these reports. 

471 

472 If there has been no reaction/event affecting the child/fetus, the parent-child/fetus report does not apply; i.e., the B.1 fields below 

473 apply only to the parent (mother or father) who experienced the adverse reaction/event. 

474 For those cases describing miscarriage or fetal demise or early spontaneous abortion, only a parent report is applicable, i.e., the 

475 B.1. fields below apply to the mother. However, if suspect drug(s) were taken by the father this information should be indicated in 

476 the field B.4.k.13. 

477 If both the parent and the child/fetus sustain adverse events, two separate reports, i.e., one for the parent (mother or father) and 

478 one for the child/fetus, should be provided but they should be linked by using sections A.1.12 in each report. 

479 

480 If only the child/fetus has an adverse reaction/event (other than early spontaneous abortion/fetal demise) the information provided 

481 in this section applies only to the child/fetus, and characteristics concerning the parent (mother or father) who was the source of 

482 exposure to the suspect drug should be provided in section B.1.10. 

483 

484 If both parents are the source of the suspect drug(s) then the case should reflect the mother’s information in section B.1.10 and the 

485 case narrative (section B.5.1) should describe the entire case, including the father’s information. 

486 

487 B.1.1 Patient (name or initials) 

488 User Guidance: 

489 

490 It is important that this field is populated. The identification of the patient may be prohibited by certain national confidentiality 
E2B(R) Electronic Transmission of Individual Case Safety Reports 

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491 laws or directives. The information should be provided when it is in conformance with the confidentiality requirements. This also 

492 applies to medical record number(s) (B.1.1.1).

493 If the initials of the patient are unknown to the sender, this field should be populated with “UNKNOWN”. 

494 If the initials are known to the sender but cannot be transmitted due to data privacy requirements, this field should be populated 

495 with “PRIVACY”. 

496 

497 B.1.1.1 Patient medical record number(s) and the source(s) of the record number (if 

498 allowable) 

499 User Guidance: 

500 

501 Record numbers can include the health professional record(s) number(s), hospital record(s) number(s), or patient/subject 

502 identification number in a study. The source of the number should be specified to ensure the possibility of retrieval 

503 when possible and desirable. 

504 

505 B.1.2 Age information 

506 User Guidance: 

507 

508 Only one of the elements describing age should be used. The choice should be based upon the most precise information available.

509 

510 B.1.2.1 Date of birth 

511 User Guidance: 

512 

513 If the full date of birth is not known, an incomplete date can be used. If only an approximate age is available this 

514 information can be captured in section B.1.2.2. 

515 

516 B.1.2.2 Age at time of onset of reaction/event 

517 User Guidance: 

518 

519 If several reactions/events are in the report, the age at the time of the first reaction/event should be used. For fetal 

520 reaction(s)/event(s) the next item B.1.2.2.1 “Gestation period when reaction/event was observed in the fetus” should be 

521 used. 

522 When providing the age in decades, please note that, for example, the 7th decade refers to a person in his/her 60’s. 

523 See the companion document for format specifications. 

524 

525 B.1.2.2.1 Gestation period when reaction/event was observed in the fetus 

526 User Guidance: 

527 

528 The gestation period at the time of exposure is captured in section B.4.k.9. See the companion document for format 

529 specifications. 

530 

531 B.1.2.3 Patient age group (as per reporter) 

532 − Neonate 

533 − Infant 

534 − Child 

535 − Adolescent 

536 − Adult 

537 − Elderly

538 

539 User Guidance: 

540 

541 These terms are not defined in this document and are intended to be used as they were reported by the primary source. 

542 This section should be completed only when the age is not provided more specifically in sections B.1.2.1 or B.1.2.2. 

543 

544 B.1.3 Body weight (kg) 

545 User Guidance: 

546 

547 Body weight at the time of the event/reaction. 

548 

549 B.1.4 Height (cm) 
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550 

551 B.1.5 Sex 

552 User guidance: 

553 

554 See the companion document for format specifications. 

555 

556 B.1.6 Last menstrual period date 

557 User guidance: 

558 

559 Imprecise dates can be included, (i.e., month, and year or year only). See the companion document for format specifications. 

560 

561 B.1.7 Relevant medical history and concurrent conditions (not including reaction/event) 

562 

563 B.1.7.1 Structured information on relevant medical history including onset and resolution 

564 date as well as relevant comments. (repeat as necessary) 

Disease / surgical 

procedure / etc. 

Start date Continuing 

Y/N/U 

End 

date 

Comment

s 

Family 

history Y 

 

565 

566 User Guidance: 

567 

568 Medical judgment should be exercised in completing this section. Information pertinent to understanding the case is desired (such 

569 as diseases, conditions such as pregnancy, surgical procedures, psychological trauma, risk factors, etc.). In case of prematurity, the 

570 birth weight should be recorded in the comments. Each of the items in the table can be repeated as appropriate. If precise dates 

571 are not known and a text description aids in understanding the medical history, or if concise additional information is helpful in 

572 showing the relevance of the past medical history, this information can be included in the Comments column. In order to identify 

573 relevant medical information of the family (e.g., hereditary diseases) a flag should be added to the appropriate disease(s). 

574 MedDRA LLT code should be used in the main descriptive column for disease/surgical procedure/etc. Imprecise dates can be 

575 used for both start and end dates. See the companion document for format specifications for the continuing column. 

576 

577 B.1.7.2 Text for relevant medical history and concurrent conditions (not including 

578 reaction/event)

579 User Guidance: 

580 

581 If structured information is not available in the sender’s database, this field should be used. Otherwise, it is preferable to 

582 send structured data in segment B.1.7.1. 

583 

584 B.1.8 Relevant past drug history (repeat as necessary) 

585 

Name of drug 

as reported 

MedID PhPID Start date End date Indication Reactions 

 

586 User Guidance: 

587 

588 This segment concerns drugs previously taken. It does not concern drugs taken concomitantly or drugs which might have 

589 potentially been involved in the current reaction(s)/event(s). Information concerning concomitant and other suspect drugs should 

590 be included in section B4. The information provided here can also include previous experience with similar drugs. Medical 

591 judgment should be exercised in completing this section. When completing the item concerning the name of the drug, it is 

592 important to use the words provided by the primary source. Trade name, generic name or class of drug can be used. 

593 To standardise this information, the ICH M5 guideline should be used. Based on the medicinal product name as reported by the 

594 primary source, the most specific identifier, being either the Medicinal Product Identifier (MedID) or the Pharmaceutical Product 

595 Identifier (PhPID) should be provided. If a MedID and a PhPID for the reported medicinal product are not available, this field 

596 should be left blank. 

597 The term "none" should be used when there is no previous exposure to the drug or vaccine. 

598 MedDRA LLT code should be used in the Indication and Reaction columns. In the event of previous exposure to drug(s) or 

599 vaccine(s) without reaction, the MedDRA code “No adverse drug effect” should be used in the Reaction column. Imprecise dates 

600 can be used for both start and end dates. 

601 
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602 B.1.9 In case of death 

603 B.1.9.1 Date of death 

604 User Guidance: 

605 

606 An imprecise date can be used. See the companion document for format specifications. 

607 

608 B.1.9.2 Reported cause(s) of death (repeat as necessary) 

609 User Guidance: 

610 

611 MedDRA LLT code should be used 

612 

613 B.1.9.3 Was autopsy done? 

614 Yes/No/Unknown 

615 

616 B.1.9.4 Autopsy-determined cause(s) of death (repeat as necessary) 

617 User Guidance: 

618 

619 MedDRA LLT code should be used 

620 

621 B.1.10 For a parent-child/fetus report, information concerning the parent 

622 User Guidance: 

623 

624 This section should be used in the case of a parent-child/fetus report where the parent had no reaction/event. See user guidance for 

625 section B.1. Guidance regarding confidentiality is provided in B.1.1, and should be considered before providing the parent 

626 identification. For the subsections B.1.10.4 through B.1.10.8, the guidances provided for B.1.3 through B.1.5 and B.1.7 through

627 B.1.8 should be reviewed. 

628 

629 B.1.10.1 Parent identification 

630 

631 B.1.10.2 Parent age information 

632 User Guidance: 

633 

634 The date of birth should be used if the precise birthday is known; otherwise the age should be used. 

635 

636 B.1.10.2.1 Date of birth of parent 

637 User Guidance: 

638 

639 If the full date of birth is not known, an incomplete date can be used. See the companion document for format 

640 specifications. 

641 B.1.10.2.2 Age of parent 

642 

643 B.1.10.3 Last menstrual period date 

644 User Guidance: 

645 

646 A full precision date should be used. See the companion document for format specifications. If a precise date is not 

647 available, the gestation period at time of exposure in B.4.k.9 should be completed. 

648 B.1.10.4 Body weight (kg) of parent 

649 B.1.10.5 Height (cm) of parent 

650 B.1.10.6 Sex of parent 

651 

652 B.1.10.7 Relevant medical history and concurrent conditions of parent (not including 

653 reaction/event) 

654 B.1.10.7.1 Structured information (parent)(repeat as necessary) 

Disease / surgical procedure/ 

etc. 

Start date Continuing 

Y/N/U 

End date Comments 

 

655 
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656 User Guidance: 

657 

658 MedDRA LLT code should be used in the main descriptive column for disease/surgical procedure/etc. 

659 

660 B.1.10.7.2 Text for relevant medical history and concurrent conditions of 

661 parent (not including reaction/event) 

662 B.1.10.8 Relevant past drug history of parent (repeat as necessary) 

Name of drug 

as reported 

MedID PhPID Start date End date Indication Reactions (if any and 

known) 

 

663 

664 User Guidance: 

665 

666 To standardise this information, the ICH M5 guideline should be used. Based on the medicinal product name as reported by the 

667 primary source, the most specific identifier, being either the Medicinal Product Identifier (MedID) or the Pharmaceutical Product 

668 Identifier (PhPID) should be provided. If a MedID and a PhPID for the reported medicinal product are not available, this field 

669 should be left blank. MedDRA LLT code should be used in the Indication and Reaction columns. 

670 

671 

672 B.2 Reaction(s)/event(s) 

673 User Guidance: 

674 

675 The designation of “i” in this section indicates that each item is repeatable and that it corresponds to the same “i” in all 

676 subsections. A separate block (i) should be used for each reaction/event term. For example, if two reactions are observed, the first 

677 reaction would be described in items B.2.1.0 through B.2.1.6, and the other reaction would be described in items B.2.2.0 through 

678 B.2.2.6. 

679 

680 B.2.i.0 Reaction/event as reported by the primary source 

681 User Guidance: 

682 

683 The original reporter's words and/or short phrases used to describe the reaction/event should be provided. These can 

684 also be included in the narrative B.5.1. 

685 

686 B.2.i.1 Reaction/event in MedDRA terminology 

687 User Guidance: 

688 

689 Only the MedDRA Lowest Level Term (LLT) most closely corresponding to the reaction/event as reported by the 

690 primary source should be provided. In the exceptional circumstance when a MedDRA term cannot be found the sender 

691 should use good clinical judgment to complete this item with the best MedDRA approximation (see MedDRATM TERM 

692 SELECTION:POINTS TO CONSIDER). MedDRA terms should be provided as code. 

693 

694 B.2.i.2 Term highlighted by the reporter and seriousness at event level 

695 

696 B.2.i.2.1 Term highlighted by the reporter 

697 

698 - yes, highlighted by the reporter 

699 User Guidance: 

700 

701 A highlighted term is a reaction/event that the primary source indicated was a major concern or reason for reporting the 

702 case. If the information is not explicitly provided by the initial reporter the term should not be considered a highlighted 

703 term. 

704 

705 B.2.i.2.2 Seriousness criteria at event level (more than one can be chosen) 

706 - Results in death 

707 - Is life-threatening 

708 - Requires inpatient hospitalization or prolongation of existing hospitalization 

709 - Results in persistent or significant disability/incapacity (as per reporter's opinion) 

710 - Is a congenital anomaly/birth defect 
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711 - Other medically important condition 

712 User Guidance: 

713 

714 The seriousness criteria of the reaction/event should be based on the definitions provided in the ICH E2A and E2D 

715 guidelines. 

716 

717 B.2.i.3 Date of start of reaction/event 

718 User Guidance: 

719 See the companion document for format specifications. 

720 

721 B.2.i.4 Date of end of reaction/event

722 User Guidance: 

723 

724 This field should include the date corresponding to the date the reaction/event is assessed as resolved/recovered or 

725 resolved/recovered with sequelae (B.2.i.6). 

726 

727 B.2.i.5 Duration of reaction/event 

728 User Guidance: 

729 

730 This section can usually be computed from start/end of reaction/event. Both dates and duration can be useful (e.g., for a 

731 reaction/event of short duration such as anaphylaxis or arrhythmia). 

732 Imprecise dates can be used. See the companion document for format specifications. 

733 

734 B.2.i.6 Outcome of reaction/event at the time of last observation 

735 − recovered/resolved 

736 − recovering/resolving 

737 − not recovered/not resolved 

738 − recovered/resolved with sequelae 

739 − fatal 

740 − unknown 

741 

742 User Guidance: 

743 

744 In case of irreversible congenital anomalies the choice not recovered/not resolved should be used. 

745 “Fatal” should be used when death is possibly related to the reaction/event. Considering the difficulty of deciding 

746 between "reaction/event caused death" and "reaction/event contributed significantly to death", both were grouped in a 

747 single category. Where the death is unrelated, according to both the reporter and the sender, to the reaction/event, death 

748 should not be selected here, but should be reported only under section B.1.9. 

749 

750 B.3 Results of tests and procedures relevant to the investigation of the patient 

751 User Guidance: 

752 

753 This section should capture the tests and procedures performed to diagnose or confirm the reaction/event, including those tests

754 done to investigate (exclude) a non-drug cause (e.g., serologic tests for infectious hepatitis in suspected drug-induced hepatitis). 

755 Both positive and negative results should be reported. While structured information is preferable, provisions have been made to

756 transmit the information as free text in B.3.2. 

757 

758 B.3.1 Structured information (repeat as necessary)

Date Test Result Unit Normal low range Normal high range More information 

available (Y/N) 

759 

760 User Guidance: 

761 

762 Imprecise dates can be used; units and normal ranges should be in free text unless covered by a controlled vocabulary. The 

763 column entitled "more information available" accepts only yes or no (see the companion document for the appropriate format). 

764 “Yes” means that more documentation is available upon request e.g., ECG strips, chest Xray. “No” means that no more 

765 documentation is available. 

766 MedDRA LLT codes should be used to code test names. 
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767 If results and units cannot be split, B.3.2 should be used. More than one test can be included in B.3.2. 

768 

769 B.3.2 Results of tests and procedures relevant to the investigation 

770 

771 

772 B.4 Drug(s) information 

773 User Guidance: 

774 

775 This section covers both suspect drugs and concomitant medications (including biologics). In addition, the section can be used to 

776 identify drugs thought to have an interaction. For each drug, the characterization of the drug role (B.4.k.1) is that indicated by the 

777 primary reporter, (i.e., the original source of the information) and the sender. The designation of ”k” in this section indicates that 

778 each item is repeatable and that it corresponds to the same “k” in all subsections. A separate block (k) should be used for each 

779 drug. Drugs used to treat the reaction/event should not be included here. 

780 

781 B.4.k.1 Characterization of drug role 

782 Suspect / Concomitant / Interacting / Drug Not Administered / Blinded 

783 User Guidance: 

784 

785 This field contains the characterization of the drug as provided by primary reporter or if this information is missing, by 

786 the sender. All spontaneous reports should have at least one suspect drug (see Section 1.5). If the reporter indicates a 

787 suspected interaction, “interacting” should be selected. All interacting drugs are considered to be suspect drugs. 

788 

789 “Drug not administered” can be used for example in two circumstances: 

790 - in clinical trial: if the adverse event occurred after the informed consent was signed but prior to the administration 

791 of the study drug e.g., during the screening period or the washout procedure. In general the adverse event should be 

792 reported as due to the trial procedure. In that case, the rest of the section B.4 should be left blank and the 

793 information on the suspect cause of the event should be provided in the section B.5. 

794 - medication error: if the patient did not receive the actual prescribed drug but another one, repeatable section B.4 

795 should be completed with the information about the prescribed drug (including the fact that it was not 

796 administered), as well as the information on the dispensed drug as the “suspect” drug. 

797 

798 “Blinded”: 

799 The ICH E2A guideline recommends that the case safety reports with blinded therapy should not be reported. However, 

800 if it is important to exchange a case safety report during a clinical trial, this value should be used. In that case the fields

801 of the section B.4.k.2 Drug identification should be populated with the characteristics of all the blinded study drug(s). 

802 

803 B.4.k.2 Drug identification 

804 User Guidance: 

805 

806 Medicinal product names and active ingredient names should be provided as they were reported. To standardise this 

807 information, the ICH M5 guideline should be used. In case of investigational drugs, only a code might be known and 

808 provided. If more than one active ingredient is specified, each should be included in item B.4.k.2.2,and can be repeated 

809 as necessary. 

810 

811 B.4.k.2.0 Medicinal product unique identifier 

812 User Guidance: 

813 

814 Based on the medicinal product name as reported by the primary source, the most specific identifier either the Medicinal 

815 Product Identifier (MedID) or the Pharmaceutical Product Identifier (PhPID) should be provided. If a MedID and a 

816 PhPID for the reported medicinal product are not available, this field should be left blank. 

817 

818 B.4.k.2.0.1 MedID and MedID operation date 

819 B.4.k.2.0.2 PhPID and PhPID operation date 

820 

821 B.4.k.2.1 Medicinal product name as reported by the primary source 

822 User Guidance: 

823 

824 The name should be that used by the reporter. It is recognized that a single product can have different proprietary names 

825 in different countries, even when produced by a single manufacturer. 
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826 

827 B.4.k.2.2 Active ingredient identifier (repeat as necessary) 

828 User Guidance: 

829 

830 Each active ingredient should be specified individually by repeating this section. For each active ingredient, the ICH M5 

831 active ingredient TermID should be provided if available. If the active ingredient TermID is not available, the INN or 

832 the active ingredient name or the drug identification code should be provided. 

833 

834 B.4.k.2.2.1 Active ingredient name 

835 B.4.k.2.2.2 Active ingredient TermID and TermID operation date

836 

837 B.4.k.2.3 Identification of the country where the drug was obtained. 

838 User Guidance: 

839 

840 See the companion document for the appropriate codes and format. 

841 

842 

843 B.4.k.3 Holder and authorization/application number of drug 

844 User Guidance: 

845 

846 If the ICH M5 MedID is not available for the reported medicinal product, the name of the holder should be provided 

847 with the authorization number in the country where the drug was obtained when the case report is sent to that country. 

848 These items apply to both applications and authorizations. Pharmaceutical companies should provide this information 

849 for their own suspect drug(s). 

850 

851 B.4.k.3.1 Authorization/Application Number

852 B.4.k.3.2 Country of authorization/application

853 User Guidance: 

854 

855 See the companion document for the appropriate codes and format. 

856 

857 B.4.k.3.3 Name of holder/applicant 

858 

859 B.4.k.4 Structured Dosage Information (repeat as necessary)

860 (e.g., 2 mg three times a day) 

861 B.4.k.4.1 dose (number) 2 

862 B.4.k.4.2 dose (unit) mg 

863 B.4.k.4.3 number of separate dosages 3 

864 B.4.k.4.4 number of units in the interval 1 

865 B.4.k.4.5 definition of the interval unit day 

866 

867 User Guidance: 

868 

869 For B.4.k.4.2 the dose unit should be provided in accordance with the ICH M5 units and measurements controlled 

870 vocabulary if available. For each unit, the respective TermID and the TermID operation date should be specified. Please 

871 note the above side-by-side illustration of how the structured dosage should be provided. For the more complex 

872 example of 5mg (in one dose) every other day, subsections B.4.k.4.1 through B.4.k.4.5 would be 5, mg, 1, 2, day, 

873 respectively. In the same way, 50mg daily would be 50, mg, 1, 1, day. 

874 

875 In the case of a parent-child/fetus report, the dosage section applies to the parental dose. 

876 If any of these pieces of information is unknown, the field should be left blank. 

877 For a dosage regimen that involves more than one dosage form and/or changes in dosage, the information should be 

878 provided in section B.4.k.4.10 as text. Categories for "definition of the interval unit" are described in attachment 1 

879 

880 B.4.k.4.6 Date of start of drug 

881 

882 B.4.k.4.7 Date of last administration

883 User Guidance: 
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884 

885 For ongoing drug administration after the onset of the reaction/event, this item should be blank and Action(s) taken with 

886 drug (B.4.k.11) should be used. 

887 

888 B.4.k.4.8 Duration of drug administration

889 User Guidance: 

890 

891 This item should be used if exact dates of drug administration are not available at the time of the report, but there is 

892 information concerning the duration of drug administration. The information requested is the overall duration of drug 

893 administration and covers intermittent administration. See the companion document for the appropriate format. 

894 

895 B.4.k.4.9 Batch/lot number 

896 User Guidance: 

897 

898 This information is particularly important for vaccines and biologics. The most specific information available should be 

899 provided. For expiration date and other related information, see additional information on drug (B.4.k.13). 

900 

901 B.4.k.4.10 Dosage text 

902 User Guidance: 

903 

904 This item should be used in cases where provision of structured dosage information is not possible. 

905 

906 B.4.k.5 Cumulative dose to the reaction/event 

907 User Guidance: 

908 

909 The cumulative dose provided should be the total dose administered until the first sign, symptom or reaction. Where 

910 possible, cumulative dose to the reaction/event should be structured as follows: (For standardised units see the user 

911 guidance of B.4.k.4.2.) 

912 

913 B.4.k.5.1 cumulative dose to first reaction (number) 

914 B.4.k.5.2 cumulative dose to first reaction (unit) 

915 

916 B.4.k.6 Pharmaceutical Dose form 

917 User Guidance: 

918 

919 Pharmaceutical dose form should be provided as TermID using the ICH M5 pharmaceutical dose form controlled 

920 vocabulary. If the pharmaceutical dose form TermID is not available, free text in B.4.k.6.1 should be used. 

921 

922 B.4.k.6.1 Pharmaceutical dose form 

923 B.4.k.6.2 Pharmaceutical dose form TermID and TermID operation date

924 

925 B.4.k.7 Route of administration 

926 User Guidance: 

927 

928 Route of administration should be provided as TermID using the ICH M5 Route of administration controlled 

929 vocabulary. If the route of administration TermID is not available, free text in B.4.k.7.1 should be used. For a parent930 child/fetus report, this indicates the route of administration of a drug given to the child/fetus. This is usually an indirect 

931 exposure, such as transmammary, but can include more usual routes of administration for other drugs given to the child. 

932 The parent’s route of administration should be provided in B.4.k.8. 

933 

934 B.4.k.7.1 Route of administration 

935 B.4.k.7.2 Route of administration TermID and TermID operation date

936 

937 B.4.k.8 Parent route of administration (in case of a parent child/fetus report) 

938 User Guidance: 

939 

940 This section should be used in a parent-child/fetus report and linked parent reports to indicate the route of 

941 administration to the parent. The parent route of administration should be provided as TermID using the ICH M5 Route 

942 of administration controlled vocabulary. If the Route of administration TermID is not available, free text in B.4.k.8.1 
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943 should be used. 

944 

945 B.4.k.8.1 Parent Route of administration 

946 B.4.k.8.2 Route of administration TermID and TermID operation date

947 

948 B.4.k.9 Gestation period at time of exposure 

949 User Guidance: 

950 

951 The gestational age at the time of the earliest exposure should be used. Gestation period at time of exposure should be 

952 expressed by providing both a number and designation of units of days, weeks, months or trimester. See the companion 

953 document for format specifications. 

954 

955 B.4.k.10 Indication for use in the case (repeat as necessary)

956 User Guidance: 

957 

958 The indication as reported by the primary source should be provided in B.4.k.10.1. The MedDRA LLT code should be 

959 used in B.4.k.10.2. 

960 

961 B.4.k.10.1 Indication as reported by the primary source 

962 B.4.k.10.2 Indication in MedDRA terminology (LLT code) 

963 

964 B.4.k.11 Action(s) taken with drug 

965 - Drug withdrawn 

966 - Dose reduced 

967 - Dose increased 

968 - Dose not changed 

969 - Unknown 

970 - Not applicable 

971 

972 User Guidance: 

973 

974 These data, taken together with the outcome of the reaction (B.2.i.6), provide the information concerning dechallenge. 

975 “Not applicable” should be used in circumstances such as when the patient has died or the treatment had been 

976 completed prior to reaction/event. 

977 

978 

979 B.4.k.12 Drug-reaction(s)/event(s) matrix (repeat B.4.k.12.1 through B.4.k.12.4 as necessary)

980 B.4.k.12.1 Reaction(s)/event(s) assessed 

981 User Guidance: 

982 

983 Generally the reaction(s)/event(s) assessed are ordered from the most important or the most serious to the least 

984 important. MedDRA LLT code should be used. 

985 

986 B.4.k.12.2 Relatedness of drug to reaction(s)/event(s) (repeat B.4.k.12.2.1 through B.4.k.12.2.3 as 

987 necessary) 

988 User Guidance: 

989 

990 This section provides the means to transmit the degree of suspected relatedness of each drug to the reaction(s)/event(s). 

991 The repeating items could also be used to provide the assessment of relatedness by different sources or methods of 

992 assessment. For the purpose of reporting, there is an implied suspicion of causality for spontaneous reports. It is 

993 recognized that information concerning the relatedness, especially for spontaneous reports, is often subjective and might 

994 not be available. 

995 • The following example illustrates the extensive functionality contained in this section. 

996 • Assume a patient being treated with two medications: Drug A and Drug B. 

997 • Assume the patient has had three adverse events: Event 1, Event 2, and Event 3 

998 • The reporter provided assessment of causality for events 1 and 2 for both Drug A and Drug B, but not for either drug 

999 concerning event 3. The reporter’s assessment of causality is based on overall impression, which the sender codes as 

1000 “global introspection”. 

1001 • The sender applies two methods of causality assessment, one with an algorithm (coded algorithm) and the other a 
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1002 bayesian analysis that provides a decimal probability (coded Bardi) but the sender does so only for the drug the sender 

1003 manufactures (in this case Drug A). 

1004 • From the above there are 4 sets of data for the reporter (2drugsX2eventsX1method of assessment) and 6 sets for the 

1005 sender (1drugX3eventsX2methods of assessment) for a total 10 sets of data. 

1006 • The appropriate item with the information is B.4.k.12 2(and its 3 subfields 1-3). In this example, k is replaced by Drug 

1007 A and Drug B respectively. Please note the subfields 1-3 are repeatable. Thus: 

1008 

B.4.k.12.1 B.4.k.12.2.1 B.4.k.12.2.2 B.4.k.12.2.3 

k(1) = DRUG A

reporter global introspection related 

company algorithm possibly related 

event1 

company Bardi 0.76 

reporter global introspection not related 

company algorithm possibly related 

event2 

company Bardi 0.48 

event3 company algorithm unlikely related 

company Bardi 0.22 

k(2) = DRUG B

event1 reporter global introspection not related 

event2 reporter global introspection not related 

1009 

1010 The order of the rows is not important since each one represents a complete set, however, the E2B message and M2 

1011 specifications state that all assessments for Drug A (k=1) should appear before Drug B (k=2). 

1012 For subsection B.4.k.12.1 MedDRA LLT codes should be used. Subsections B.4.k.12.2.1 through B.4.k.12.2.3 do not 

1013 call for a standardised methodology.

1014 

1015 B.4.k.12.2.1 Source of assessment (e.g., initial reporter, investigator, regulatory agency, company) 

1016 B.4.k.12.2.2 Method of assessment (e.g., global introspection, algorithm, Bayesian calculation). 

1017 B.4.k.12.2.3 Result 

1018 

1019 B.4.k.12.3 Time intervals between drug administration and start of reaction/event 

1020 User Guidance: 

1021 

1022 The major uses of intervals are to cover circumstances both in which the dates are known but the interval is very short 

1023 (e.g., minutes, such as in anaphylaxis), and in which only imprecise dates are known but more information concerning 

1024 the interval is known. Dates if available, should be transmitted in the appropriate items, rather than intervals. If the 

1025 sender wants to provide time intervals as well then the first day of administration should be counted as “1”. 

1026 The complexity of using intervals highlights the desirability of providing dates. See the companion document for format 

1027 specifications. 

1028 

1029 B.4.k.12.3.1 Time interval between beginning of drug administration and start of reaction/event

1030 

1031 B.4.k.12.3.2 Time interval between last dose of drug and start of reaction/event

1032 

1033 B.4.k.12.4 Did reaction recur on readministration? 

1034 - yes/no/unknown 

1035 User Guidance: 

1036 

1037 Unknown indicates that a rechallenge was done but it is not known whether the reaction recurred. This field should not 

1038 be completed if it is unknown whether a rechallenge was done. 

1039 

1040 B.4.k.13 Additional information on drug 

1041 User Guidance: 

1042 

1043 This should be used to specify any additional information pertinent to the case that is not covered by above sections 

1044 (e.g., beyond expiration date, batch and lot tested and found to be within specifications). This item can also be used to 

1045 provide additional information concerning the indication for the drug. For cases where the suspect drug was taken by 

1046 the father, this should be indicated in this field as e.g., Drug taken by the father. 
E2B(R) Electronic Transmission of Individual Case Safety Reports 

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1047 

1048 B.5 Narrative case summary and further information (repeat as necessary)

1049 

1050 B.5.1 Case narrative including clinical course, therapeutic measures, outcome and additional 

1051 relevant information 

1052 User Guidance: 

1053 

1054 A focused, factual and clear description of the case should be given, including the words or short phrases used by the reporter. 

1055 

1056 B.5.2 Reporter's comments 

1057 User Guidance: 

1058 

1059 This item should be used to include the reporter's comments on the diagnosis, causality assessment or other issues considered 

1060 relevant. 

1061 

1062 B.5.3 Sender's diagnosis/syndrome and/or reclassification of reaction/event (repeat as necessary)

1063 User Guidance: 

1064 

1065 This section provides the sender with an opportunity to combine signs and symptoms that were reported into a succinct diagnosis. 

1066 The reasoning would be included in section B.5.4. MedDRA LLT code should be used. 

1067 

1068 B.5.4 Sender's comments 

1069 User Guidance: 

1070 

1071 This section provides information concerning the sender's assessment of the case and can be used to describe disagreement with,

1072 and/or alternatives to the diagnoses given by the initial reporter. In case of linkage of multiple ICSRs using A.1.12, the reason 

1073 should be provided in these comments. 

1074 

1075 

1076 

1077 3. GLOSSARY 

1078 Parent-child/fetus report: Report in which the administration of medicines to a parent results in a 

1079 suspected reaction/event in a child/fetus. 

1080 

1081 Receiver: The intended recipient of the transmission. 

1082 

1083 Reporter: Reporter is the primary source of the information, i.e., the person who initially reports the facts. 

1084 This should be distinguished from the sender of the message, though the reporter could also be a sender. 

1085 

1086 Sender: The person or entity creating the message for transmission. Although the reporter and sender can 

1087 be the same person, the function of the sender should not be confused with that of the reporter. 
E2B(R) Electronic Transmission of Individual Case Safety Reports 

 - - 22

1088 

1089 ATTACHMENT 1 

1090 

1091 Definition of Interval List 

1092 Minutes 

1093 Hours 

1094 Days 

1095 Weeks 

1096 Months 

1097 Years 

1098 Cyclical 

1099 As necessary 

1100 Total 
E2B(R) Electronic Transmission of Individual Case Safety Reports 

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1101 ATTACHMENT 2 

1102 

1103 Examples of how to populate fields relevant to identifying cases and their reports 

1104 The figure provides an example of how one would populate the fields relevant to identifying cases and their reports. 

1105 Patient XX suffers three separate adverse events (AE1, AE2, AE3) spaced over a time period.

1106 

1107 Example of a simple single report from a company to a regulator 

1108 Hospital X reports AE1 to Company K who then in turn sends ICSR1 to Regulator. Population of relevant fields for 

1109 this case is illustrated in the first row of the table. Company K populates A.1.0.1 with Company K’s (case) safety 

1110 report unique identifier “JP-K-001”. 

1111 Company K populates A.1.10.2 with “JP-K-001” because company K is the initial sender of the report. Because 

1112 there has not been a previous E2B/M2 electronic report, the identifiers in A.1.0.1 and A.1.10.2 are the same.

1113 

1114 Example of company to company to company to regulator transmission 

1115 Hospital X reports AE1 to Company B who then in turn sends ICSR2 to Company C. 

1116 Population of relevant fields for this case is illustrated in the second row of the table. Company B populates A.1.0.1 

1117 with Company B’s (case) safety report unique identifier “JP-B-001”. 

1118 Company B populates A.1.10.2 with “JP-B-001” because company B considers itself the initial sender of the report 

1119 because it is unaware that Company K also sent an ICSR for this case. 

1120 Company C sends ICSR3 to Company D. The third row of the table indicates how Company C populates the relevant 

1121 fields. Company C populates A.1.0.1 with “JP-C-001”. 

1122 Company C populates A.1.10.2 with “JP-B-001”, leaving the field unchanged from the way Company B 

1123 populated it. In addition, Company C populates A.1.11.1 (Source of the case identifier) with the name of company B, 

1124 “B”. A.1.11.2 is populated with Case Identifier in the Previous Transmission by Company B “JP-B-001”. 

1125 Company D sends ICSR4 to Regulator. The fourth row of the table indicates how Company D populates the relevant 

1126 fields. Company D populates A.1.0.1 with “JP-D-001”. Company D retains in fields A.1.10.2, A.1.11.1, and 

1127 A.1.11.2 the information populated by Company C, and Company D adds to the retained information in repeatable 

1128 field A.1.11.1 “C” to represent that Company C is another source of the case identifier, and Company D adds in field 

1129 A.1.11.2 “JPC-001” to represent Company C’s case identifier from the previous transmission. 

1130 

1131 Example of a simple single report with follow-up from a company to a regulator 

1132 Hospital X reports AE1 to Company E who then in turn sends ICSR5 to Regulator. Population of relevant fields for 

1133 this case is illustrated in the fifth row of the table. Company E populates A.1.0.1 with Company E’s (case) safety 

1134 report unique identifier “JP-E-001”. Company E populates A.1.10.2 with “JP-E-001” because company E is the 

1135 initial sender of the report. 

1136 Because to Company E’s knowledge, there has not been a previous E2B/M2 electronic report, the identifiers in 

1137 A.1.0.1 and A.1.10.2 are the same. 

1138 ICSR6 represents Hospital X’s follow-up information about AE1 to Company E. Company E submits follow-up to 

1139 ICSR5 to the regulator. The relevant fields, A.1.0.1 and A.1.10.2, are populated the same as for ICSR5. ICSR6, a 

1140 follow-up report, is differentiated from ICSR5 by A.1.7, Date of Receipt of the Most Recent Information for this 

1141 Report.

1142 

1143 Example of Linking Two Separate Adverse Events Affecting the Same Patient 

1144 Patient XX later suffers a separate adverse event, AE2. Hospital X reports AE2 to Company K who then in turn 

1145 sends ICSR7 to Regulator. Population of relevant fields for this new case is illustrated in the seventh row of the 

1146 table. Company K populates A.1.0.1 with Company K’s (case) safety report unique identifier “JP-K-002”. Company 

1147 K assigns a new (case) safety report unique identifier “JP-K-002” because “JP-K-001”, as described above, represent 

1148 a separate adverse event. Company K populates A.1.10.2 with “JP-K-002” because company K is the initial sender 

1149 of the report. Because there has not been a previous E2B/M2 electronic report, the identifiers in A.1.0.1 and A.1.10.2 

1150 are the same. The previous report from Company K, “JP-K-001”, for patient XX should be represented in A.1.12, 

1151 Identification Number of the Report which is Linked to this Report. 

1152 In a contrasting example, Hospital X also reports AE2 to Company F. Company F had not previously received an AE 

1153 concerning Patient XX, and therefore there is no linked report and A.1.12 is not populated. As in the first example 

1154 concerning ICSR1, ICSR8 is a simple single report from a company to a regulator. 

1155 

1156 Example of Linking Three Separate Adverse Events Affecting the Same Patient
E2B(R) Electronic Transmission of Individual Case Safety Reports 

 - - 24

1157 Patient XX later suffers a third, separate and distinct adverse event, AE3. Hospital Y reports AE3 to Company K 

1158 who then in turn sends ICSR9 to Regulator. Population of relevant fields for this new case is illustrated in the ninth 

1159 row of the table. Company K populates A.1.0.1 with Company K’s (case) safety report unique identifier “JP-K-003”. 

1160 Company K assigns a new (case) safety report unique identifier “JP-K-003” because “JP-K-001” and “JP-K-002”, as 

1161 described above, represent separate, adverse events. Company K populates A.1.10.2 with “JPK-003” because 

1162 company K is the initial sender of the report. The previous reports from Company K, “JP-K-001” and “JP-K-002”, 

1163 for patient XX should be represented in the repeatable field A.1.12, Identification Number of the Report which is 

1164 Linked to this Report. 

K 

B 

E 

AE1 C D 

AE3 

ICSR1

ICSR2 ICSR3

ICSR6(follow-up)

K 

ICSR8

FU ICSR5(initial)

R 

ICSR4

Patient HP 

XX

Company 

X 

X K 

Y

ICSR7 AE2

F 

ICSR9

T

i

m

e

AE: Adverse Event report(case) 

HP: Hospital observing the event 

 Report of AE 

 ICSR report 

FU : Follow up 

1165 
E2B(R) Electronic Transmission of Individual Case Safety Reports 

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Tabular representation of fields contents for the above examples 

 A.1.0.1. A.1.10.2 A.1.11.1 A.1.11.2 A.1.12 

 

ICSR1(K) JP-K-001 JP-K-001 

ICSR2(B) JP-B-001 JP-B-001 

ICSR3(C) JP-C-001 JP-B-001 B JP-B-001 

ICSR4(D) JP-D-001 JP-B-001 B JP-B-001 

 C JP-C-001 

ICSR5(E) JP-E-001 JP-E-001 *

ICSR6(E) JP-E-001 JP-E-001 *

ICSR7(K) JP-K-002 JP-K-002 JP-K-001 

ICSR8(F) JP-F-001 JP-F-001 

ICSR9(K) JP-K-003 JP-K-003 JP-K-001 

 JP-K-002 

*These cases have different dates of most recent information (A.1.7) 

1166 

1167 

1168