Adverse Event Report Form and Guidelines For Non-serious and Serious Adverse Events Related to Raltegravir in IMPAACT P1097

Transcription

1 Adverse Event Report Form and Guidelines For Non-serious and Serious Adverse Events Related to Raltegravir in IMPAACT P1097 The Adverse Event Report (AER) form is used to collect initial and follow-up information for non-serious and serious adverse events for patients participating in a Merck-sponsored study anywhere in the world. All serious adverse events are to be reported to Merck & Co., Inc. within 24 hours of when first learned by the site (initial and follow up reports). Complete the Clinical Study Adverse Event form and fax to Merck within 1 business day. The following guidelines explain how to complete the AER form. Ensure that all relevant medical information necessary to support the AE term(s) is provided. Page 1 of 20

2 A. General Information Note: Fields shaded in dark gray in the table below have already been populated in AER form and clinical sites for IMPAACT P1097 do not need to fill out these sections of the form. Field Name Description Compound ID Full Name of Primary Investigator Site # Initial Follow-Up Date Reported to Merck By Study Site Protocol # Enter the generic name of the test product, if one is known, otherwise state the MK#, V#. Enter the full name of the primary investigator. Enter only the site number designated to the site Indicate whether the report is the initial report (first time SAE is reported), or if it is a follow up. Note: see section J for instructions on using the form to report follow up information Enter the date the information included in this report was reported to Merck by the study site. Enter the protocol number assigned to the study (3 digit number + suffix) The base protocol is indicated with the suffix -00. Extensions and amendments are indicated in 2 additional digits (e.g., -01 for the first amendment, - 10 for the first extension, and -21 for the first amendment to the second extension). E.g., (protocol #15, extension #1 Person Reporting Event Complete Study Title Enter the name of the individual from the study site who is reporting the event. Enter the title of the study, as stated in protocol. Note: This field will auto-fill, when the form is completed on-line (based on the compound ID and protocol # entered above). Page 2 of 20

3 B. Patient Information Field Name Allocation # Baseline # Age Sex Weight Pregnant Weeks of Gestation Description Enter the allocation number of the patient (postrandomization). For P1097, add the PID# in this space. Enter the baseline number assigned to the patient (only when a randomization number has not been assigned pre-treatment period). Enter the patient s age at the time of the onset of the AE. Enter Male or female. Enter the weight of the subject at the time of study initiation and circle the unit type (Kg, Lb). Circle Y if the patient was pregnant at the time of exposure to the study therapy. Circle N if the patient was not pregnant at the time of exposure to the study therapy. Circle U if it is unknown whether or not the patient was pregnant at the time of exposure to study therapy. Note: In IMPAACT P1097, registering the mother's pregnancy in the Antiretroviral Pregnancy Registry is encouraged, but not required. If the pregnancy is registered, please enter the number on the AER form. Enter the number of weeks gestation at the time that the patient initiated study drug therapy. Page 3 of 20

4 C. Adverse Event(s) Field Name Adverse Event(s) Description List the verbatim adverse event term(s) Symptoms (e.g., fever, abdominal pain, etc.) may be all that is available when the SAE is first reported. If this is the case, submit the initial report with the signs and symptoms that met the serious criteria listed as AE terms; update the form accordingly with the diagnosis, and submit as a follow up report. When only the death of the subject is known (no cause or AE has been yet determined), enter the term death as the AE term. Once the cause is known, the correct AE term can then be listed. List all serious as well as non-serious AEs associated with the event. Note for P1097: A recurrence of the same AE, an AE related to the originally reported event, or a new serious event occurring for the mothers prior to discharge from the hospital or for the infants through 14 days after birth should be a follow-up to the original AE report. These events do not need to be reported under a new report. Note: Although an AE can result in hospitalization or lead to surgery or diagnostic testing, the hospitalization, surgery or diagnostic procedure is, in and of itself, not the AE. The event, not the hospitalization or procedure, should be listed as the AE term. In addition, hospitalization for elective surgery for a preexisting condition which has not worsened while on therapy with study drug is not an AE. If the patient died, record probable cause(s) of death as AE(s) OR if the death is unknown, record death as the AE term. Once the cause of death is known, replace the term death with the AE(s) that caused the death of the patient. Page 4 of 20

5 AE Onset Date AE Stop Date Relationship to Study Drug Outcome Enter the date of onset of the signs or symptoms related to the adverse experience. Note: For hospitalization cases, the onset date of the SAE may be prior to the date of hospitalization. Enter the date on which the subject/patient was determined to have completely recovered or recovered with sequelae from the reported adverse event i.e., Causality Enter Y if the investigator considered that there was a reasonable possibility that the adverse event may have been caused by the study drug. Enter N if the investigator felt that the patient s experience was not related to the study drug. NOTE: If causality = N for raltegravir, do not report the adverse event to Merck. Enter U, if the causality is unknown because the investigator did not report it or because the investigator has yet to make an assessment. If the AE report is derived from the CRF, use the following convention for rating causality on the AER form: 5 Definitely drug related: Y 4 Probably drug related: Y 3 Possibly drug related: Y 2 Probably not drug related: N 1 Definitely not drug related: N Enter the outcome of the adverse experience as: 1 Recovered 2 Recovered with Sequelae* 3 Not Recovered Sequelae: The signs/symptoms of the reported AE have not completely resolved and a new baseline for the subject/ patient is established since full recovery is not expected If the AE report is derived from the CRF, use the following convention for outcome: Page 5 of 20

6 CRF Term Recovered/Resolved Recovered/Resolved with sequelae Recovered/Not Resolved Recovering/Resolving Fatal Unknown AER Term Recovered Recovered with sequelae Not Recovered Not Recovered Not Recovered Not Recovered Page 6 of 20

7 Did the AE Result In (Enter Yes or No for each AE): Death * Hospitalization or Prolongation of Existing Hospitalization Persistent or Significant Disability Enter Y, if the AE resulted in the patient s death. Enter N if the patient did not die as a result of the AE. Enter U if it is unknown if the AE resulted in the patient s death. Do not leave blank. * Additional information is required. See below. Enter Y if the AE resulted in inpatient admission to the hospital or if the AE prolonged inpatient hospitalization. Enter N if the patient was not hospitalized, or was only seen in the emergency room. Enter U if it is unknown whether the SAE resulted in hospitalization or prolongation of hospitalization. Do not leave blank. Note: Hospital discharge diagnoses should be listed as adverse experiences, as appropriate. Enter Y if the AE resulted in a substantial disruption of a person s ability to conduct normal life functions. Enter N if the AE did not result in a substantial disruption of the person s ability to conduct normal functions Enter U if the AE is unknown. Do not leave blank. Page 7 of 20

8 Is the AE (Enter Yes or No for each AE) Life-Threatening Cancer Due to an Overdose Congenital Anomaly Enter Y if the AE placed the patient at immediate risk of death from the experience as it occurred. Note: It does not include a reaction that, had it occurred in a more serious form, might have caused death. For example, drug-induced hepatitis which can be fatal would not be considered life threatening unless the patient almost died from it. It also does not include a chronic condition that might result in decreased life expectancy. Enter N if the AE was not life threatening. Enter U if the AE is unknown. Do not leave blank. Enter Y if the AE is a cancer or worsening of a preexisting cancer. Enter N if the AE is not a cancer or worsening of a preexisting cancer. Enter U if unknown. Do not leave blank. Enter Y if the reporter term is the result of an overdose. Note: If an adverse event is related to an overdose and related to raltegravir, this event should be reported to Merck. Enter N if the AE is not the result of an overdose. Enter U if unknown Do not leave blank. Enter Y if the AE is a congenital anomaly in the offspring of the patient (male or female) exposed to the drug or vaccine. Enter N if the AE is not a congenital anomaly in the offspring of the patient (male or female) exposed to the drug or vaccine. Enter U if unknown Do not leave blank. Page 8 of 20

9 Other Medical Event Other Medical Event is also known as OME. Enter Y if the AE is determined by the reporter to be an other important medical event Note: Other Important Medical Event is defined as an event that may not result in death, be lifethreatening, or require hospitalization but that based upon appropriate medical judgment, may jeopardize the subject/patient and may require medical or surgical intervention to prevent one of the outcomes listed previously. Examples of other important medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home; blood dyscrasias; convulsions that do not result in an in-patient hospitalization; the development of drug dependency; the development of drug abuse. The term OME reflects changes in patient care as a result of new technology and procedures. Enter N if the AE term does not meet the definition of Other Medical Event. Enter U if it is unknown whether or not the AE term meets the definition of Other Medical Event. Do not leave blank. * Complete the following fields only when patient dies Date of Death Autopsy Autopsy Results Relevant to the AE Did AE Diminish after stopping suspect therapy? Enter the date the patient died. Indicate whether or not an autopsy was performed. Enter the autopsy results that are relevant to the AE terms reported, as stated in the autopsy report/death certificate. Update the list of AE terms above to include those stated in the Autopsy report, as appropriate. Check Yes if the suspect therapy was stopped after the onset of the AE and the patient s symptoms improved. If Yes, specify which of the AE terms listed diminished after stopping the suspect therapy. Check No if the suspect therapy was stopped after the onset of the AE, and the patient s symptoms did not improve. Check N/A if study therapy was not stopped after the Page 9 of 20

10 Did AE reappear after restarting suspect therapy? NOTE (all fields): onset of the AE or if the AE occurred pre- or posttherapy. Check Yes if an AE reappeared after re-starting suspect therapy. If Yes, specify which AE reappeared after re-starting suspect therapy. Check No when the AE did not reappear after restarting suspect therapy. Check N/A when: The drug is continued. The patient died while on therapy. The drug was discontinued before the onset of the AE. The drug was not restarted. All fields initially answered as U for unknown, should be updated with definitive information prior to closure of the SAE case Page 10 of 20

11 D. Laboratory Results/Diagnostic Tests List relevant laboratory or diagnostic tests and results which would support the AE term reported and the outcome (pre-, during, and post- adverse event/study therapy). List in chronological order when possible. Indicate units, normal ranges and whether the test result was normal or not. Field Name Name of Lab/Diagnostic Test Date Value/Results Units Normal Range Comments (Normal/Abnormal) Description Enter the name of the lab or diagnostic test. Enter the date the test was administered. Enter the value or results of the test. Enter the units of the test results. Enter the normal range of the test results. Enter results from diagnostic tests, which are not numerically calculated. Page 11 of 20

12 E. Medical History Field Name Concurrent Conditions Medical History Description List all pertinent medical conditions that developed either prior to the initiation of drug therapy and that were still present at the time of the adverse event, or that represent a chronic condition that developed after the onset of the study, that was previously reported as an AE, and that remained unresolved prior to onset of the SAE being reported (e.g., diabetes mellitus, carcinoma). List all other medical history relevant to the AEs reported that occurred prior to the earliest adverse experience onset date but which would not necessarily be considered concurrent conditions (e.g., myocardial infarction, CABG). Page 12 of 20

13 F. Suspect Therapy Field Name Primary Suspect Therapy Secondary Suspect Therapy or Other Merck Therapy Field Name Formulation Description Note: For P1097, this should be raltegravir. Provide the names of any additional therapies which the investigator felt may have been related to the adverse event. For reports originating from non-u.s. sites, provide the generic name of the secondary suspect drug/other Merck therapy. If a Merck product is listed here for a study patient who experienced a serious adverse experience, provide the causality for the product in the narrative. Description Provide the appropriate formulation for each drug listed, e.g., tab, cap, or inj. Route Provide the route by which each drug was administered, e.g., P.O., I.V., or I.M. Indication for Use Strength Frequency Total Daily Dose at Time of AE Start Date Stop Date Note: For P1097, this should be HIV infection. Provide the dosage strength of the drug including units (e.g., mg). Provide the frequency of dosing, e.g., b.i.d., q8h. Provide the total daily dose that the patient was taking at the time of the AE. The total daily dose should equal the strength times the frequency. For combination drugs, list the total daily dose of both of the components of the capsule or tablet separated by a dash (e.g., for 1 tablet of VYTORIN 10-20, list instead of 1 tablet ). Provide the date that the patient received the first dose of the medication. For studies, do not give the start date of the latest phase of the study, but the actual start date of the study therapy. For multiple doses, i.e., vaccines provide the date of the first dose as the start date. If the drug was discontinued because of the AE, provide the date that the patient received the last dose Page 13 of 20

14 Action Taken of the medication. If the patient continued therapy, list CONT. No stop date should be provided for drugs that are continuing at the time of the report. If the drug was interrupted because of an AE, provide the date that therapy was interrupted as the stop date. In the event that therapy was continued until death, provide the date of death as the stop date. If you are not sure if therapy continued, enter U for unknown. If known, provide the action taken (by the treating physician or by the patient) regarding the suspect drug relative to the adverse event. 1 = None 2 = Discontinued 3 = Dosage reduced 4 = Dosage interrupted Page 14 of 20

15 G. Concomitant Therapy Field Name Concomitant Therapy Daily Dose Start Date Stop Date Indication for Use Description Provide all therapies (U.S. reports, enter U.S. trade name; non-u.s. reports, enter generic name) given within 14 days prior to the onset of the AE. Note: Do not include therapies provided to treat the AE. These therapies should be listed in the narrative of the AER. For each concomitant therapy listed, provide the total daily dosage of the drug. For each concomitant therapy listed, provide the date that the patient received the first dose of the medication. If the start date is an approximate date, indicate approx next to the date. If the start date is unknown, enter UNK. Provide the date that the patient discontinued therapy. Enter CONT if the patient continued therapy. PLEASE DO NOT LIST A DASH (-). Provide the reason that the patient was taking the concomitant therapy. Be sure to include the indication as a concurrent condition as appropriate. Page 15 of 20

16 H. Narrative and Comments Summarize information that is pertinent to the understanding of the SAE. Pertinent information includes, but is not limited to: the subjective verbatim information (e.g., signs and symptoms) provided by the investigator, the objective information (e.g., diagnostic tests and results) gained through clinical evaluation, the treating physician s assessment (e.g., physician s diagnosis, hospital discharge diagnosis, etc.), the physician s plan (e.g., action taken as a consequence of each AE including medications to treat the AE), and the patient s outcome relative to each SAE as well as the overall patient outcome (e.g., recovered, died, etc.). If critical data is not obtainable, the narrative should specifically state this information ie, cardiac enzymes results are not available The presence of the following 15 elements in the narrative allows for an independent assessment of the clinical course of the patient: 1. Concomitant medication (within 14 days of AE) 2. Start date of the study therapy (In P1097, this is raltegravir.) 3. Daily dose 4. Route of Administration 5. Indication for use for each suspect therapy 6. Supporting evaluations, signs and symptoms and/or diagnostic tests and results to corroborate each AE term reported 7. Stop date of the study therapy 8. Action taken as a result of each AE term reported 9. Dechallenge and/or rechallenge information 10. Information on treatment provided (for each AE term) 11. If the patient was hospitalized, the hospital discharge diagnosis is included in the narrative 12. If an SAE resulted in death, information on whether or not a post-mortem evaluation was performed, the cause of death, and its possible relationship to the study therapy 13. Resolution of each AE term 14. Causal relationship assessment by the investigator 15. Evidence that the SAE was closed (e.g., presence of the statement no additional information is expected in the narrative) See attached Narrative Template. Page 16 of 20

17 I. Administrative Section Field Name Full Address of Primary Investigator Reporting Study Staff Signature Description Enter the address of the Primary Investigator. Section to be completed by Study Site individual completing the form (when used to report SAE case). Field Name Date Description Section to be completed by Study Site individual completing the form (when used to report SAE case). The following fields are to be completed by the Merck & Co., Inc. contact only: Received By (Name/Signature) Date First Learned by Merck Medical Review Completed By Date Enter the name of the Merck employee who received the data reported on the AER form from the site. Include the signature in the hard copy version to be filed in the Official Regulatory File (ORF). Enter the appropriate date for this version of the report (initial or follow up). This is for Merck Personnel Only: Enter the name of the person who performed the medical review of the AER and the date of review. Include the signature and date of review in the hard copy version to be filed in the Official Regulatory File (ORF). If the approval is provided electronically (i.e., via ), print a copy of the , attach to the AER form and forward to ORF with the completed AER form. Enter the date that Medical Review was completed. Page 17 of 20

18 J. Follow Up Information When using this form in hard copy (filling out manually), follow up information may be provided on a new form such that only new information and/or changes to existing information is provided. Sections A, B and I need to be completed for every version created. There is no need to re-enter all other information provided on a previous version(s). When completing the form electronically, follow up information may be added to the existing form in the pertinent sections. New information and/or revisions to existing information should be clearly identified (e.g, bold text in field added/changed, in narrative start statement with new information received on XX/XX/XX, ) Page 18 of 20

19 Please refer to the following template to assist in the preparation of the narrative: Note: any pertinent information that is specified in this narrative template, but not available at the time the version is prepared, should be identified as such. NARRATIVE TEMPLATE Initial information has been received from (the reporting investigator or coordinator) concerning the following report: PID#, a year old (male /female) with, and (concurrent conditions) and (a) history of (medical history) who on (DD- MM-YYYY), entered IMPAACT P1097. On (DD-MM-YYYY), the patient was placed on raltegravir therapy (dosage/usage e.g. 50 mg tablet, 50 mg daily) for treatment of (indications). Concomitant therapy included (add relevant concomitant medications). On (DD-MM-YYYY), the patient experienced (SAE symptoms) and was hospitalized on (DD-MM YYYYY) if hospitalized On (DD-MM-YYYY) his/her physical examination showed (pertinent examination and related to SAE). On (DD-MM-YYYY), the lab (lab name) results revealed (lab examination detailed result). If applicable: During the hospitalization, the patient developed a (condition) which the investigator considers to be an NSAE] On (DD-MM-YY), the patient was diagnosed with. The condition was treated with (list relevant treatment provided). On (DD-MM- YYYY), raltegravir was (discontinued/ continued/ interrupted). The patient was recovering (did not recover) from (list AE terms). If applicable: On (DD-MM-YYYY), the patient was discharged from the hospital. The discharge diagnosis was. If the pt died: A post-mortem evaluation <was/was not> done on this patient and the cause of death was determined to Page 19 of 20

20 be which was assessed to be <related/nonrelated> to treatment (state for each SAE reported) The reporting investigator considered that the (SAE) was (definitely, probably, possibly, probably not, definitely not) related to therapy with (any suspected therapy, if appropriate). Additional information is <expected/no further information is expected> (choose which statement applies). For follow up reports add the following statement to original report: Follow up information has been received from the investigator on (DD-MM-YY). (state any changes about age, gender, dose, frequency, route of administration, indication, therapy start date, AE onset date, serious criteria, outcome, dechallenge, rechallenge, concomitant therapy, concurrent condition / medical history, laboratory / diagnostic tests, reconfirmed causality and outcome in another attachment if space limited). On DD-MM-YY, (labs name) showed (if any new information). At the time of reporting, the patient was recovering (did not recover) from. The investigator considered the SAE(s) was/were (definitely, probably, possibly, probably not, definitely not) related to study therapy. NOTE: Consider the following for inclusion in the narrative, when relevant: 1) If hospitalization consisted of observation only, include this fact in the narrative 2) Hospital discharge diagnosis not available at the time of the report. 3) If SAE resulted in death, provide a statement regarding the status of autopsy results. 4) If subject/patient not on concomitant therapy, state so in the narrative Page 20 of 20