Adverse Drug Event Reporting - Essay Example

PHARMACOVIGILANCE - CASE STUDY Part 1: Track the journey of this adverse event report from the moment it was experienced by the patient to its eventual inclusion in regulatory reports, outlining all possible steps and timings along the way. Explain any assumptions you make when constructing this answer, and describe any issues you consider relevant to this journey. Adverse drug event reporting is a significant event, which can make a difference on the safety of a drug. When adverse drug reporting is done at the clinical trial stage, the event becomes more substantial since it prevents possible adverse effect on the wider population. Adverse events on a product must be communicated amongst the investigators, the sponsors and the institutional review board (IRB). This case study is about a pharmaceutical product called Product X, which is marketed, in many countries globally including US, EU and Japan. A patient was admitted to hospital following an adverse event he experienced while taking Product X as part of a clinical trial. The Investigator sends a detailed adverse event report to the clinical trial sponsor (U.S. Department of Health and Human Services, et al., 2009) A number of steps were followed to report this adverse event from the moment it was experienced by the patient to its eventual inclusion in regulatory reports. There different step took varying periods to be accomplished. The amount of time taken before reporting is often determined by the seriousness of the adverse event. In case of life threatening adverse event, which put the patient at the immediate risk of death, all the reporting should be done promptly in not more than 7 calendar days (U.S. Department of Health and Human Services, et al., 2009) In case of serious adverse event, which results in hospitalization like in case of Product X the reporting, should be prompt since the adverse event may develop into a life-threatening one. Suspected adverse events or reactions are treated with less seriousness since they are considered less serious. In case the adverse event is unexpected, which is an effect that the investigators or the sponsors had not anticipated, the reporting should be prompt since the level of seriousness is not certain. Therefore, the investigators and sponsor reviewed the safety information for product X to enable them decide the seriousness of the adverse event. This was crucial in determining the urgency of reporting. In this case study, the assumption made is that the adverse event of Product X was serious since it resulted in hospitalization. The reporting was done urgently since the adverse event could have been life threatening (U.S. Department of Health and Human Services, et al., 2009) After the investigator realizes that the drug has caused adverse event on the patient, the first step is to send a detailed adverse event report to the clinical trial sponsor. The reporting should be done promptly. The investigator should be able to identify the adverse effects that are resultant from use of Product X. In our case, the investigator was supposed to report the adverse effect immediately since it was alarming as it had led to admission of the patient.  On receiving the report, the sponsor carried out literature review regarding Product X. While the review is under progress, the sponsor communicated to the Food and Drug Administration (FDA) as well as all the other investigators participating in the drug trial. The investigator included those in US, EU and Japan. The reporting should be done in form of written IND safety report. The report described any adverse events experienced by the patient that could be associated with usage of Product X. Both serious and unexpected effects should be included in the report. Additionally, the sponsor’s report should include findings from the previous test conducted on laboratory animals that suggested the product could be of risk when used by humans (U.S. Department of Health and Human Services, et al., 2009) The reporting by the sponsor should be a continuous process since they are supposed to keep updating all the investigators of any new observations discovered or reported by the participants including the patient under discussion. In order to compile a precise report, the sponsor reviewed all the information pertaining to the safety of Product X. the safety information included any data received from domestic as well as foreign sources where Product X was under clinical trial. Additionally, the sponsor reviewed information regarding clinical as well as epidemiological investigations done on laboratory test animals as well as other vitro studies. Other relevant sources that the sponsor reviewed included scientific literature and unpublished scientific papers regarding Product X. Since the drug was undergoing trial in other region of the world, the sponsor referred to report from foreign regulatory authorities regarding product X (U.S. Department of Health and Human Services, et al., 2009). Since the adverse event was assumed to be serious, the sponsor reported to FDA and participating investigators within a period of fifteen calendar days. However, if more adverse events had been discovered to make the problem life threatening, the sponsor would have reported to FDA in a period of 7 calendar days. In the report, the sponsor identified all IDN reports that could have been submitted by any of the investigators of Product X to FDA. The sponsor presented the IND safety report in a format that FDA could access. The exact format guidelines were provided by FDA . In case of foreign suspected adverse reactions, the sponsor presented the report on a Council for International Organizations for Medical Sciences (CIOMS). When the investigators received the information from the sponsor, they were supposed to compile a report of all the unanticipated problems as well as risks that product X was likely to cause on humans as well as other test animals. Unanticipated adverse events were also included in the report. To ensure that the report was helpful, the investigators collaborated to in ensuring they provided adequate explanations on how different events were unanticipated problems. This was crucial since it would ensure that the report sent to FDA was informative. The report was prepared and sent promptly to IRB. Only the unanticipated adverse events were included in the report sent to FDA (U.S. Department of Health and Human Services, et al., 2009). On receiving the report, the FDA started evaluation on all the data regarding product X. FDA makes use of experts to gather all the information regarding the manufacture of the drug. FDA informs the investigators and participants on the issues regarding Product X that are under review. Using the information provided, the FDA investigated the seriousness of the problem to decide whether the drug trials would continue. If FDA was not satisfied with the information provided, it was free to request for more information from the investigators or the sponsor. Any further information requested by FDA should be reported as soon as possible and not later that 15 calendar days. In this case, the assumption is that the safety information provided was adequate. Additionally, it is assumed that FDA found the adverse event to be serious or life threatening. Due to the seriousness of the adverse event, the report was included in regulatory reports. In this case FDA was supposed to include the report on the regulatory report. Additionally, the event was reported to the investigators and the study sponsor. Depending on any other reported adverse events regarding Product X, FDA would take additional actions which could include label change in case the drug was harful to certain groups of individuals. FDA could also send a warning to HCPS. In case the sponsor had reported more adverse events, FDA would consider terminating the clinical trials and withdrawal of the product in the domestic as well as foreign countries where trials were undergoing. In some cases ligation would occur if the investigators or sponsor did not follow the required procedures. However, if the problem was less serious which would depend on presence or absence of other cases of adverse events, FDA would still include the reporting in regulatory reports. However, the investigation would continue but under scrutiny. Additionally, the investigators would be required to alter the clinical testing. The above procedure assumes that the investigator who identified the adverse event was in U.S. and that the reporting was done within U.S. Another assumption made is that Product X is a drug under clinical trial (U.S. Department of Health and Human Services, et al., 2009). Part 2: Discuss the factors that could influence the decision whether or not to incorporate the event into the global risk management plan for Product X.  Several factors could influence the decision whether to incorporate the event regarding product X on the global risk management plan. There is no specific number of reports required for an event to be considered a global concern. However, evaluation of the seriousness of the event and other reporting that could have been made before or during the investigation period will determined the seriousness with which the problem will be treated. Addionally, product X was being used in several countries which required that it generates rare and adverse reactions to be considered a global risk. However, Product X was still under clinical trial and any adverse events would be treated seriously to avoid possible legalization of a risky product. For an adverse event to be considered of global concern, the potential risks of a product should be serious. The number of complaints that the sponsor of product X had receive, it could be possible to identify the potential risk of continuing with clinical trials for product X. The seriousness of the event could be determined by number of domestic and foreign safety reports that the sponsor and FDA will have received by the end of the investigation. If numerous and serious adverse events regarding Product X had been identified, the chances of incorporating the event in global risk management plan would increase. Another factor to be considered is the seriousness of the identified risk. In case of product X, the identified risk was serious since it had resulted in hospitalization of a clinical trial participant. In Case the adverse event became life-threatening or resulted in death of the patient of other trial participant during the investigation period, the event would be incorporated in the global risk management plan. An additional factor that would determine if Product X was incorporated in global risk management plan is the risk factors associated with continued clinical trial of product X. This would be determined by the identified adverse events in laboratory animals, anticipated effect, unanticipated effects as well as fatal or other serious events that could have occurred since the start of the clinical trials. When deciding if to incorporate the event in global risk management plan, FDA will consider the size of population that participated in the clinical trial. If the trial was done on a large population, and few adverse events were reported, then the event could be flagged off and not included in the global risk management plan. However, if the percentage of adverse events reported were high the event was likely to be included in global risk management plan. Another factor that would determine if the event was considered a global risk is the number of known serious risk associated with the use of Product X. this could be obtained from the safety information recorded by the sponsor and all the investigators. The risks related to the product could have been identified using the laboratory test animal or during the clinical trials. If the risks were serious and contributed to the adverse event in the patient under study, then the event would be incorporated in global risk management plan. This would ensure that the investigators are more vigilant as they continue with the clinical trials. Another factor that could determine if the event was incorporated in global plan for risk management is the level of consistency and severity of the adverse event. In case the event was not listed in the investigators brochure, which is also known as unanticipated adverse event, it would be treated more seriously as compared to events that are consistent with prior observations. An extra factor that would determine how seriously the problem is treated is the relevance of the event to the clinical trial. By this I mean if the event is related to the clinical trial. The adverse event could have resulted from other causes and not use of Product X. in such cases, the event would be flagged off. However, if the event was relevant to the clinical trial, it would be treated depending on its seriousness and level of relevance to the clinical trial. If lethal or fatal, it would be incorporated in the global risk management. Another factor that would determine the seriousness of the problem is whether the study was in accordance with research ethics. The researchers must have obtained full and informed consent from the authorities to conduct the trial. Additionally, the participants must have agreed to participate in the study voluntarily. Additionally, the investigators as well as the sponsor must demonstrate they protected the rights of the participants. If the above or other ethical issues were not observed, the event could be incorporated in the global risk management plan. Part 3: Describe the process by which this event and a suitable warning would be added to the reference safety information for Product X.   There are different ways in which a warning about product X would be added to reference safety information. One way would be through early communication on the ongoing investigation. Assuming that the patient with the adverse event was in United States, FDA would inform the investigators and participants of the possible risk associated with continued use of product X. Another way of passing the warning would be through public health advisories who would be informed of the adverse event. The advisories would be requested to participate in the investigation to identify the level of risk associated with use of Product X. A warning would also be sent to the manufacturer to stop further manufacturing of product X or take precautionary measure depending on the causal of the adverse event. The process of adding the above adverse event to the reference safety information involves some stages. The first stage is to compile a summary of identified risks of Product X. the summary should include any outstanding questions on the safety of Product X that require or are under investigation. The summary should also include other adverse events that could have been identified before or during the investigation period. Other aspects to be included include the seriousness of the adverse event under discussion and its relevance to the clinical trial. The next stage of adding the above event to the reference safety information should involve determination of the level of toxicity of the product. This should include a brief description of the side effects associated with use of product X. The toxicity should be clearly defined in term of how the product may affect different body systems at different dosages. Any other information regarding toxicity of product X should be included in the safety information. The next stem of adding the event to reference safety information should be stating the groups at most risk if any. The information could be determined from the investigators brochure, which contains observations made when the drug was used on different groups of people. Additionally, some information on interaction between product X and other drugs should be included in the safety information. Another aspect to consider is the potential risks of using Product X. this shoul involve gathering of all the evidence that made the event to be considered hazardous. The process should involve clear description of how the adverse event was associated with product use. Basically, this should give a description of the investigation process by FDA. A brief description of pharmacodynamics and pharmacokinetic interactions should be given. The next process of adding the adverse event resulting from product X to the reference safety information should involve discussing the epidemiology of the product. This should include information regarding the population that participated in the clinical trials. The data should include their age, sex, ethnicity as well as race. Data regarding the difference in reactions across the different groups should be provided. Additionally, if there were any adverse events in other regions where clinical trials were done, they should be described. Another aspect to include in the reference safety information is relevant safety information that could have been obtained from other clinical trials if any. Results from all the ongoing trials and other trials on product X that may have occurred earlier should be included in the safety reference safety information. Works Cited U.S. Department of Health and Human Services, et al., 2009. Guidance for Clinical Investigators, Sponsors, and IRBs Adverse Event Reporting to IRBs Improving Human Subject Protection. [Online] Available at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126572.pdf [Accessed 7 Nov 2012]. Read More