Mrs. Mary Patient visited her General Practitioner/Family Physician, Dr. Greta Provider last week because she was suffering from a severe urinary tract infection (UTI). Dr. Provider prescribed a course of Ciprofloxacin 250mg tablets to be orally taken twice a day for 5 days. Mrs. Patient's only other regular medication is hormone replacement therapy, for which she takes Prempak C 625micrograms.

After three days, Mrs. Patient's UTI is resolving well, but she is experiencing increasing soreness of her left ankle. She has no recollection of injuring her ankle in any way. On the fourth day, her ankle is so sore that she makes another appointment to see Dr. Provider later that day. Dr. Provider examines Mrs. Patient and observes that her left ankle is red, stiff, hot and swollen. Mindful of Mrs. Patient's comments that she has no recollection of doing anything that might have injured her ankle, Dr. Provider wonders what other causes there might be for these symptoms. Remembering that she prescribed an antibiotic for a urinary tract infection on Monday for Mrs. Patient, she checks her clinical software for Mrs. Patient's medication record and sees the prescription for Ciprofloxacin. She then checks the electronic drug formulary for information on Ciprofloxacin and Quinolone antibiotics as a family, and it reminds her that Quinolones are known to have an adverse effect of tendonitis, especially of the Achilles tendon. The formulary advises that the medicine should be stopped immediately and the affected joint rested.

Dr. Provider's clinical judgment leads her to be confident that Mrs. Patient is experiencing an adverse drug reaction to her treatment for her UTI. She explains this to Mrs. Patient, and that she must stop the Ciprofloxacin (she feels that the UTI has resolved well), and rest her ankle, and that the ankle soreness will resolve. She may take some painkiller medication (paracetamol/acetaminophen) if she would like to. However, she would like to see her again in a week just to be sure all is well. One week later, Mrs. Patient sees Dr. Patient again. Her ankle is improving nicely and she feels that in a couple of days she will be back to normal. After she has left, Dr. Provider thinks through this incident, and decides that, due to the severity of the event she should report it to a patient safety/quality improvement organization, the relevant drug manufacturer, and regulatory authority. She logs into her clinical support system to complete an electronic Individual Case Safety Report form. The electronic form already includes many of the details of Mrs. Patient's adverse drug event. The form appears on the screen, with some of her relevant information already filled in e.g., Mrs. Patient's demographic information, relevant medical history, lab tests and results and current medications. The form includes Dr. Provider's progress notes and other sections ready for her input. When Dr. Provider is satisfied that the form is complete, she then authorizes her clinical support system to send the electronic report to the appropriate organization(s).

Interaction: Individual Case Safety Report Create(PORR_IN049006)

Product Problem Reporting

This storyboard is provided to help illustrate how the ICSR can be used for product problem reporting. Note that the ICSR interactions are the same as those used to support adverse event reporting.

Rebecca Pharmacist is preparing a solution to be used in chemotherapy for patients in General Hospital's outpatient cancer clinic. She notices, as she holds up a bottle from storage, that the solution appears cloudy and has particles floating in it. This physical property is not according to specification and she sets the bottle aside. At the end of the day, a more thorough inspection reveals that half the bottles in a case of Solution X contain contaminated or defective solution. She reports the problem to the medical supply department and the hospital risk manager sends a product problem report to the regulatory authority and to the manufacturer.

Interaction: Individual Case Safety Report Create (PORR_IN049006UV)

This storyboard is a revised report based upon the storyboard for PORR_SN040001UV01)

Last week, Dr. Greta Provider submitted an Individual Case Safety report that referred to Mrs. Mary Patient's adverse drug experience with Ciprofloxacin as a treatment for UTI. As she reviews the records of the case, it seems to her that perhaps the fact that Mrs. Patient was an ardent runner could be a relevant factor in evaluating the cause of her recent tendonitis. Dr. Provider decides to send a revised ICSR so that this additional information will be considered when Mrs. Patient' case is evaluated by the appropriate organization(s).

Interaction: Individual Case Safety Report Revise: (PORR_IN049007)

Request for Nullification

This storyboard is not based on any real world event and is being provided to help demonstrate support of the use case.

Mr. Law, JD is an attorney specializing in private injury work. He has recently been putting together a class action suit seeking damages for patients who had been taking the drug, CureAll, as a treatment for lower back pain. However, in a fraction of cases, while the back pain had improved, patients had experienced severe headaches. Mr. Law, and his clients, believe that CureAll is responsible and they are seeking damages.

As Mr. Law's office signs up users of CureAll as parties to this lawsuit, they also file an ICSR for each new client. This report includes the relevant information regarding the individual case. Such a report was filed when the office agreed to represent Patient A, who stated that he was a long time CureAll user and headache sufferer.

After further discussions with Patient A, it emerges that had started experiencing headaches long before his use of CureAll, and may be related to trauma he experienced as a child when he was kicked by a horse. Once it becomes clear that CureAll cannot reasonably be involved, Patient A is informed that he is being dropped from the suit. Mr. Law's office also sends an ICSR retraction to the local regulatory agency to nullify this report.

Interaction: Individual Case Safety Report Retraction (PORR_IN049008UV)

Shortly after the submission of the ICSR product problem report for Solution X (storyboard PORR_STN040002UV01), General Care Hospital receives a call from the Acme Supply Company, whom also received a copy of the ICSR product problem report. The Acme representative informs the hospital that based upon the lot number reported in the ICSR, this product could not be one of theirs because the product lot number in the report violates Acme's lot number convention for assigning lot identifiers. The hospital's medical supply department representative reviews the paperwork for deliveries from Acme Supply, and locates the correct bill of lading for the product delivery in question. With the proper lot information in hand, the medical supply department informs the hospital risk manager that a corrected ICSR product problem report needs to be sent to the regulatory authority and manufacturer.

Interaction: Individual Case Safety Report Revise: (PORR_IN049007)

Request for Nullification: Product Problem Report

This storyboard uses the same ICSR nullify interaction used for adverse event reporting..

RealFixit Corporation, a medical device manufacturer, reports a serious injury to the FDA for a patient who underwent major abdominal surgery. This manufacturer learned later that their product did not cause or contribute to the patient's injury; however another company's product caused the patient's injury. The RealFixit Corporation forwards a request to retract their original device problem report since their product did not contribute to the injury. The manufacturer of the other suspected problem device submitted a serious injury report also.

Interaction: Individual Case Safety Report Retraction (PORR_IN049008UV)

Device Adverse Event Report

This storyboard provides an example of the submission of a medical device adverse event report or a device-related procedure. The storyboard was created by FDA Center for Device and Radiological Health (CDRH) to illustrate the reporting of device-related events using a fully electronic, two-way communication ICSR process between senders and receivers of ICSR reports. Some FDA capabilities described in this storyboard are not currently available.

The Event

On December 12, 2005 Eve Everywoman, a 54 year old female was admitted to the Outpatient Surgery Center for the placement of a Portman Medical Corporation, Model LS 4700, implantable pain pump. In surgery, the pain pump was implanted without difficulty and was determined to be functional. After the procedure the patient was referred to the recovery area for stabilization. In the recovery room, the anesthesiologist Dr. Sally Sleeper initiated the programming of Ms. Everywoman's implanted pump. During this set-up procedure the pump stopped functioning and the pump's visual display went blank. The anesthesiologist was unable to troubleshoot the cause of the device failure, nor restore its function. The patient was informed of the device failure and opted to return to the O.R. the next day for the removal of the defective device and placement of a new pain pump. The patient was scheduled to return to the O. R. for the repeated procedure. The second Model LS 4700 implantable pain pump was implanted and completed its programming process without difficulty.

Creation of the Initial Primary Source Report

Dr. Sleeper decided to complete an electronic Individual Case Safety Report, using the hospital's Incident Reporting System because he felt his patient had suffered a serious injury. She logged into the incident reporting system and completed the necessary fields required to populate a device adverse event. The form appeared on the computer screen with a great deal of Ms. Everywoman's patient demographics, medical history and many details of her surgical case already populated because the incident reporting system references data already stored in the patient's electronic medical record. The event information was obtained from the surgeon's and the anesthesiologist's progress notes and automatically populated into the appropriate fields in the form. Once the report of the incident was completed, Dr. Sleeper clicked the submit key. This sent the incident report to the risk manager, Patient Safety Committee, the device manufacturer and the regulatory authority. Mr. Randy Riskers, the hospital risk manager, reviewed the incident report, made some edits and gave approval that this was a reportable event that could be sent to FDA. He clicked a 'Submit SMDA Event' button that electronically forwarded the ICSR report to the manufacturer. Additionally, the hospital returned the pain pump to the manufacturer for evaluation three days after the event.

Interaction: Individual Case Safety Report Create (PORR_IN049006UV)

Manufacturer Response to Reported Event - Note that this demonstrates how the Related Report class is used in the ICSR

Two weeks after the implantable pain pump was returned to Portman Medical for failure analysis, the manufacturer sent an update for the ICSR to the hospital and to the FDA. The manufacturer was able to store the hospital's source report and create a new related report in their internal Adverse Event Reporting System using the User Facility (hospital) Report as a primary source document.

Interaction: Individual Case Safety Report Complete (PORR_IN049007UV)

FDA Request for Additional Information

FDA electronically returns the ICSR report with an attached document. This correspondence is in response to information received at the Center for Devices and Radiological Health (CDRH) involving the Portman Medical Corporation, Model LS 4700 implantable pain pump implanted on December 12, 2005. The FDA requested additional information about the software issue described in the medical device report, including the steps taken to address the stated problem. The manufacturer will be given 30 days to respond to the Center's request for additional information.

Interaction: Individual Case Safety Report Create (PORR_IN049006UV)

Manufacturer Response to Request for Additional Information

Manufacturer sends new, changed or updated information via ICSR. This follow up serves to respond to CDRH's request for additional information about the software issue described in a report involving a Portman Medical Corporation, Model LS 4700 implantable pain pump implanted on December 12, 2005. The Center requested information as to the software issue described as part of the root cause analysis of the implanted pain pump's failure. The responses to the issues posed are as follows: The software issue described in this report was a result of an event that would take place only in the rare instances of high resistance of the motor, causing an excessive back EMF (Electromotive Force). This would ultimately lead to an inadvertent timeout of the internal watchdog times of the microprocessor, causing the pump to turn off prematurely. A revision to the software of the Model LS 4700 implantable pain pump has completed Portman's Engineering Design Change Process. Additionally, testing has been conducted on the software revision and no further instances of this failure have been detected. It is felt no further risk can be associated with this release of the software. Once approved, new pumps being built will contain the new software revision. FDA stores all of the information related to this event and completes appropriate review of the event.

Interaction: Individual Case Safety Report Revise (PORR_IN049007UV)

FDA Reportable Food Registry Reporting

Great Cracker Company's Plant in St Cloud, MN produces two box sizes of Great Crackers--a 12 ounce box and a family-size 18 ounce box. On July 3rd, 2008, a routine QA inspection of lots produced from July 1st through July 3rd detected a strange odor during a tasting of samples from each box. Upon further testing, it was determined that the products had been contaminated with a very deadly pesticide. The quantity of production during this time frame was 10,000 boxes of the 12 ounce size (5,000 in lot # 2008-0701-200, and 5,000 in lot # 2008-0702-201) and 8,000 boxes of the 18 ounce size Box (lot # 2008-0703-202).

Before the problem was discovered, 6,000 of the 12-ounce (5,000 from lot # 2008-0701-200 and 1,000 from the other lot) and 6,000 of the 18-ounce Boxes were shipped to a local grocery warehouse in St Paul and 1,000 of the 18-ounce boxes were shipped to another local grocery warehouse in Richmond, VA. It was determined that the adulteration was unintentional and happened at the St Cloud facility and was not due to adulterated raw materials from suppliers.

The two retail warehouses were notified on 3 July in time for the warehouses to quarantine the reportable food products.

The remaining Great Crackers were disposed of on 3 July at the St Cloud plant.

The company's risk manager and (the person who is in the FDA food facility registration database for the plant) logs into a Federal AE Portal and enters this report the evening of 3 July in compliance with 1005 legislation. His report includes the following information:

• Date food product is reportable on 3 July 2008
• The risk manager validates his FFRN and reports that the plant in St Cloud, MN is both the responsible party and the reporting site.
• Two (2) different products (12- and 18-ounce size boxes) the amount of the 12 ounce adulterated product--in both lots--was reported as was the lot amount of the 18 ounce product.
• The adulteration discovery code is 'self-discovery'.
• Both destinations of the shipments were identified and the amount shipped, by lot, to each location was reported.
• The risk manager reports that he has informed both 'down' locations of the adulteration on 3 July.
• There is no requirement for the company or the risk manager to report the origin of the raw materials, since the adulteration only took place in St Cloud.
• There is no requirement for either destination warehouse to report since they did not further distribute the reportable food prior to the notification and it was quarantined on site.
• Amount of adulterated food produced :
  • Product 1 (12-ounce box; lot # 2008-0701-200) = package type = box; size = 12 ounces; package quantity = 5,000
  • Product 1 (12-ounce box; lot # 2008-0701-201) = package type = box; size = 12 ounces; package quantity = 5,000
  • Product 2 (18-ounce box; lot # 2008-0701-202) = package type = box; size = 18 ounces; package quantity = 8,000
• Amount disposed of:
  • Product 1 (12 ounce box; lot # 2008-0701-201) - package type = box; size = 12 ounces; package quantity = 4,000
  • Product 2 (18-ounce box; lot # 2008-0701-202) - package type = box; size = 18 ounces; package quantity = 2,000
• Amount shipped:
  • To St Paul:
    • Product 1 (12-ounce box; lot # 2008-0701-200) = package type = box; size = 12 ounces; package quantity = 5,000
    • Product 1 (12-ounce box; lot # 2008-0701-201) = package type = box; size = 12 ounces; package quantity = 1,000
  • To Richmond:
    • Product 2 (18-ounce box; lot # 2008-0701-202) - package type = box; size = 18 ounces; package quantity = 6,000

Interaction: Individual Case Safety Report Create(PORR_IN049006)

Dietary Supplement Adverse Event Storyboard

Mrs. Nuclear, an 86 year old female consumed 400 IU of vitamin D made by Supplement Company IOP. Four hours later she fell to the floor and had a seizure. When she stopped seizing, her husband noted that she did not awake, and called the 911-Emergency Dispatcher. When the paramedics arrived, Mrs. Nuclear was still unconscious and she was taken to the hospital. When she arrived at the hospital, Mrs. Nuclear regained consciousness in the examination room, and the emergency room attending physician, Dr. Attend ordered a series of tests to be performed to obtain a more precise diagnosis of Mrs. Nuclear condition. Mr. Nuclear informed the attending physician that they starting taking a new vitamin D supplement, and that he suspects that Mrs. Nuclear is having an adverse reaction to the supplement. Dr. Attend responded to Mr. Nuclear that he does not suspect this to be the case, but informs Mr. Nuclear that he can report the incident to the dietary supplement company or FDA to help alleviate his suspicion. Mr. Nuclear called the FDA's Consumer Complaint hotline to report the problem, and provided a contact number for Dr. Attend for follow up once the laboratory results are final. The FDA Consumer Complaint hotline technician data entered the complaint into the system, and sent the case electronically to the FDA Center for Food and Applied Nutrition (CFSAN) for further analysis and follow up.

Interaction: Individual Case Safety Report Create (PORR_IN049006UV)

The FDA CFSAN medical officer reviewed the adverse event report submitted by Mr. Nuclear. The medical officer contacts Dr. Attend and requests that the laboratory results and discharge summary be sent to FDA for review. The medical officer provides Dr. Attend with the consumer complaint number for the case. Dr. Attend queries his clinical system and notes that Mrs. Nuclear was diagnosed as having a low potassium level and an abnormal heart beat. The discharge summary reflects that she was placed on a Potassium supplement and Digoxin. Dr. Attend updates the patient's record to include the dietary supplement Mrs. Nuclear ingested to search for drug interactions related to the ingredients of the dietary supplement. The system returned no information about drug/supplement interactions with the product made by Supplement Company IOP. Dr. Attend generates an incident report and sends the requested information to FDA electronically, noting that he does not suspect that Mrs. Nuclear hospitalization was related to the dietary supplement she ingested prior to her arrival. FDA reviews the laboratory results and discharge summary and determines that no further action is required on the case.

Interaction: Individual Case Safety Report Create (PORR_IN049006UV)

Cosmetics Adverse Event Reporting: Multiple Suspected Cases

The following two adverse events involved the same cosmetic face paint product. They occurred within a few days of each other, from different areas of the country

Wallace Wackyford, a Fun Store employee, submitted an adverse event report to the FDA to report an incident after being contacted by the principal of the Central Z Middle School. A black color face paint (item# 5), produced by Coverings Corporation, as listed on the label, was applied to the students as part of a special theme day. Approximately 300 students received an application of face paint with different brushes. The following day, approximately 70 - 80 students reported having a rash on their face. Later the number of rashes had accumulated to approximately 173. A dozen or so students sought medical treatment. Medical information was not included in the report from Mr. Wackyford. The report was sent electronically using a web-based form. The web-based form translates the information into an HL7 ICSR and routes the report to the appropriate FDA safety evaluator for analysis.

Interaction: Individual Case Safety Report Create(PORR_IN049006)

A counselor of a boy's organization called the state FDA Field Office to report an incident that occurred at their annual banquet. The counselor reported that several colors of face paint from Company Y were used to mark the cheek of each boy. A total of about 40 boys were marked in this manner using one of three colors: blue, red, and green. Of the 18 boys which received the blue face paint, a total of 16 experienced a skin reaction. This reaction ranged from a red, 'burnt' appearance which lasted about 48 hours to a raised, bright red rash which still remained 5 days later when the incident was reported to the counselor. To the knowledge of the reporter, no boy received care from a medical doctor for the problem. The FDA Field Office employee data entered the report into the Consumer Complaint System and the report was sent electronically to the FDA headquarters office for further analysis and follow up.

Interaction: Individual Case Safety Report Create(PORR_IN049006)

Parent/Child Reports: Related ICSR Reports

On 12th of July, 2003, a male child was born at full term (40 weeks gestation) with polydactyl feet (1 extra toe each foot). The mother of the child had been taking oral Propylthiouracil 200 mg once a day for Hyperthyoridism before and during early pregnancy (therapy dates 20th April 2003 to 28th June 2006). However the 30 year old mother stopped taking the drug at 12 weeks gestation as she experienced a severe skin eruption that was attributed due to the propylthiouracil. The mother's adverse event was reported to the authorities at that time and was assigned the case identifier US-Nobel-MT99101.

The obstetrician contacted the marketing authorisation holder of the medicinal product (Nobel Company) and informed them of the child's congenital anomaly due to exposure in-utero as he believed the child had receiving the drug transplacentally.

Creation of Related Child Report

The company collected all the details of the event within their own records system. An assessor from the pharmacovigilance group within the company reviewed the data and made the following comments:

Company comment: Propylthiouracil is known to cross the placental barrier in low quantities when used by the mother sometime during pregnancy. Studies have shown that the frequency of congenital malformations is higher in patients not treated for hyperthyroidism than those treated for it. The alternative treatments for hyperthyroidism of radioactive iodine and surgery are not recommended for pregnant patients.

The company completed an electronic ICSR, using their own IT system, which included a reference to the mother's related AE report id US-Nobel-MT99101, and submitted the report electronically to the regulatory agency on the 20th July 2003.

Regulatory agency response - Note that this function is outside of the ICSR standard and refers to HL7's accept acknowledgement interaction ID (MCCI_IN000002UV01)

The electronic report is received by the agency from Nobel company and it was checked against their requirements for a valid report. The report is found to be valid and a positive acknowledgement is returned to Nobel Company to confirm receipt and acceptance of the report.

Interaction: Individual Case Safety Report Create(PORR_IN049006)

The Event

In the UK a multi-centre clinical trial with the EU Clinical trial authorisation number (EUDRACT No. 2004-09102-03) is being conducted to evaluate the efficacy and tolerability of Danthium, a new substance, in post-menopausal women with breast cancer hormone receptor positive tumours. The sponsor of the trial assigned the protocol No 0105798/01.

A 50 year-old female patient was enrolled in this trial with the patient ID 125-0871 and one week after the third cycle of chemotherapy treatment with intravenous Danthium 20 mg/kg once a week, the patient developed a fever (38o C) and diarrhoea (11th May 2003). The patient was hospitalised. Blood tests were performed and the patient was discovered to have neutropenia. This adverse event was considered as serious and unexpected. Specific lab test information such as the lab test date, name, results (including structured units of measurement) and an indication of whether or not the lab test was within the normal range were included in the ICSR report. The patient was treated with G-CSF and recovered a week later. The patient is a smoker and has a family history of breast cancer. The patient was also concomitantly taking oral domeridone for Nausea.

Interaction: Individual Case Safety Report Create(PORR_IN049006)

Creation of the Clinical Trial Initial Report

The investigator responsible for the patient (Dr. Davis at Cardiff University hospital, Cardiff, Wales) informed the sponsor (Big Company) of the event and the sponsor in turn created an electronic report to submit to the appropriate regulatory authorities using their own IT system.

The company also provides their causality assessment of the case, which reflects that it is likely that the investigational medicinal product caused the reaction.

Regulatory Authority response (outside of the ICSR functionality and refers to HL7 accept acknowledgement interaction ID (MCCI_IN000002UV01)

The electronic report is received by an agency from Big Company and it is checked against their requirements for a valid report. The report is found to be valid and a positive acknowledgement is returned to Big Company to confirm receipt and acceptance of the report.

The Event

In the EU a multi-state clinical trial with the EU Clinical trial authorization number (EUDRACT No. 2004-09102-03) is being conducted in Germany and Netherlands to evaluate the efficacy and tolerability of Danthium, a new substance, in post-menopausal women with breast cancer hormone receptor positive tumors. The sponsor of the trial assigned the protocol No 0105798/01. The clinical trial authorization number assigned by the German authorities is '12345678' and the authorization number assigned by the Dutch authorities is 'NL12345.001.07'

A 50 year-old female patient with the patient ID 125-0871 was enrolled in this trial in a German centre and one week after the third cycle of chemotherapy treatment with intravenous Danthium 20 mg/kg once a week, the patient developed a fever (38o C) and diarrhea (11th May 2003). The patient was hospitalized. Blood tests were performed and the patient was discovered to have neutropenia. This adverse event was considered as serious and unexpected.

Lab Test Results:

Date________Test Name___________Test Result___Test Units____Normal Range

12/05/2003___Neutrophil Count______4.0 x10e9_____cells/l_______2.0 - 7.5

12/05/2003___WBC_______________6.8 x10e9_____cells/l_______4.0 - 11.0

19/05/2003___Neutrophil Count______0.8 x10e9_____cells/l_______2.0 - 7.5

19/05/2003___WBC_______________4.5 x10e9_____cells/l_______4.0 - 11.0

26/05/2003___Neutrophil Count______3.8 x10e9_____cells/l_______2.0 - 7.5

26/05/2003___WBC_______________6.3 x10e9_____cells/l_______4.0 - 11.0

The patient was treated with G-CSF and recovered a week later. The patient is a smoker and has a family history of breast cancer. The patient was also concomitantly taking oral domeridone for Nausea.

Interaction: Individual Case Safety Report Create(PORR_IN049006)

The investigator responsible for the patient (Dr B. Bernard at Berlin University hospital, Berlin) informed the sponsor (Big Company) of the event and the sponsor in turn created an electronic report to submit to the concerned regulatory authorities using their own IT system. The company provides the following assessment of the case: It is likely that the investigational medicinal product caused this reaction.

Regulatory Authority response - note this is outside of ICSR functionality and refers to HL7 accept acknowledgement interaction ID (MCCI_IN000002UV01)

The electronic report is received by an agency from Big Company and it is checked against their requirements for a valid report. The report is found to be valid and a positive acknowledgement is returned to Big Company to confirm receipt and acceptance of the report.