|Year : 2016 | Volume
| Issue : 4 | Page : 143-145
An introduction to pharmacovigilance: what a cardiologist must know
Sumit Munjal FRSPH, MSc, DLSHTM MRQA
Takeda Development Centre Europe Ltd., United Kingdom
|Date of Web Publication||20-Oct-2016|
Takeda Development Centre Europe Ltd., 61, Aldwych, London, WC2B 4AE
Source of Support: None, Conflict of Interest: None
The science of pharmacovigilance (PV) is important to ensure safety of patients and healthy volunteers taking medicinal products. A number of stakeholders are involved who contribute to the success of this field of medicine. One such contributor is physicians and health-care professionals who work in different therapeutic areas such as cardiology. As the understanding of this science evolves, the role of cardiologist becomes even more vital. The process of developing drugs is getting more complex, time consuming, and costly. However, several efficiencies can be achieved around accelerated drug development, cost effectiveness, risk management, managing health authority expectations, and developing personalized medicines. This is possible by increased collaboration between cardiologists and pharmaceutical medicine professionals. Therefore, it is important for a cardiologist to understand the basics of the science of PV and contribute further bringing new safe medicines to patients.
Keywords: Benefit-risk assessment, cardiology, drug development, personalized medicine, pharmacovigilance
|How to cite this article:|
Munjal S. An introduction to pharmacovigilance: what a cardiologist must know. J Clin Prev Cardiol 2016;5:143-5
According to the World Health Organization (WHO), pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem. It is a discipline that is ultimately responsible for patient safety and is considered an integral part of pharmaceutical industry. It is spread across all therapeutic areas such as cardiology, general medicine, oncology, respiratory, and endocrinology. Medicines have adverse effects, and these need to be understood well when prescribing a drug. A physician needs to assess the benefit-risk (B-R) balance of prescribing a drug to their patient.
An adverse event (AE) is a medical occurrence temporally associated with the use of a medicinal product but not necessarily causally related (International Council of Harmonisation [ICH] E2A guideline). An AE can be considered either nonserious, or if it meets one of the criteria, serious death, life threatening, hospitalization (initial or prolonged), disability, and congenital anomaly/birth defect, or other serious (important medical) event (US-Food and Drug Administration [FDA]). Another important concept is causality assessment between the AE and the drug and primarily it is determined as positive or negative for reporting a particular case to the health authorities (HAs). A case when reported by a health-care professional (HCP) such as a clinician, pharmacist, nurse, or a patient is called a spontaneous report. Whereas a case coming from a clinical trial, postapproval named patient use programs, other patient support or disease management programs would constitute a solicited report. An Individual Case Safety Report is considered valid when the four elements of an identifiable patient, an identifiable reporter, a suspect drug, and an AE are present. Related to cardiology, an adverse effect could be due to a drug given for a cardiac indication or there could be an adverse effect on the heart when a drug is given for another disease indication.
Each type of coronary heart disease medication has different adverse effects. Antiplatelet drugs can cause diarrhea, rash or itching, abdominal pain, headache, chest pain, muscle aches, and dizziness. Side effects of anticoagulants are bleeding and necrosis (gangrene) of the skin. Side effects of angiotensin converting enzyme inhibitors include cough, elevated blood potassium levels (hyperkalemia), low blood pressure, dizziness, headache, drowsiness, weakness, abnormal taste, and rash. Taking vasodilators may cause light-headedness or dizziness, increased or irregular heart rate, or headache. Side effects of calcium channel blockers include constipation, nausea, headache, rash, edema, low blood pressure, drowsiness, and dizziness. Antiarrhythmics may cause dizziness, blurred vision, anorexia, unusual taste, fatigue, nausea, and vomiting.
On the other hand, cardiotoxicity is a condition when there is damage to the heart muscle. This may be due to chemotherapy drugs, or other medications and cardiotoxicity, if severe, may lead to cardiomyopathy. Medications that may commonly cause cardiotoxicity, or cardiomyopathy, are called anthracyclines. Anthracyclines may be used to treat leukemia, lymphoma, multiple myeloma, breast cancer, sarcoma, or other cancers. Anthracyclines include drugs such as daunorubicin (Cerubidine® ), doxorubicin, doxorubicin liposome injection (Doxil® ), epirubicin (Ellence® ), idarubicin (Idamycin® PFS), and valrubicin (Valstar® ). Targeted therapy drugs that can cause damage to the heart include trastuzumab (Herceptin® ), bevacizumab (Avastin® ), lapatinib (Tykerb® ), sunitinib (Sutent® ), and sorafenib (Nexavar® ). Patients who are older, young children and women have a greater risk for cardiac toxicity. In addition, patients who have other health conditions at the same time as cancer are at increased risk. A baseline and regular assessments during treatment would help diagnose cardiac toxicity in an individual patient. These could be done with the help of clinical examination, chest X-ray, echocardiogram, electrocardiogram, multigated acquisition scan, and troponin blood tests.
A number of key organizations play a major collaborative role for PV on a global level. These are the WHO, the ICH, and the Council for International Organizations of Medical Sciences (CIOMS). Then, there are country-level regulatory agencies such as US-FDA, UK-MHRA, Japan-PMDA, China-FDA, and European Medicines Agency. The Central Drugs Standard Control Organization is the national regulatory body for Indian pharmaceuticals and medical devices and serves parallel function to other regulatory agencies. These regulators are responsible for ensuring safety, quality, and efficacy of medicines in their country or region, providing regulatory guidelines or legislation, and conducting inspection of pharmaceutical companies. There are other key stakeholders closely involved with PV such as patients, HCPs, academia, Contract Research Organizations (CROs), lawyers, and media. A close collaboration between these various bodies and stakeholders is extremely important for effective management of patient safety. Some of the recent drug withdrawals related to cardiac science and safety reasons have been cerivastatin (risk of rhabdomyolysis), cisapride (risk of fatal cardiac arrhythmias), pergolide (risk of heart valve damage), terfenadine (prolonged QT interval), valdecoxib (risk of heart attack and stroke), and sibutramine (increased risk of heart attack and stroke).
A pharmaceutical company has many different functions at a global level, one of which is the Department of Global PV (GPV). Typically, in a medium to large-size pharmaceutical organization, there are subfunctions within GPV such as medical safety, PV operations, standards compliance and training, EU-qualified person responsible for PV, drug safety officer and PV business partner relations, and risk management with pharmacoepidemiology. Most of the safety decisions taken are applicable across the globe for patients; however, there may be some local exceptions based on patient needs/characteristics, disease epidemiology, and individual country laws. These subfunctions work very closely with each other and other functions outside GPV. Pharmaceutical PV physicians work in a global matrix cross-functional team and provide medical input to manage drug safety issues such as single case safety assessment, safety signal detection, aggregate safety such as periodic safety update reports, risk management, responses to HA, support for filing new license submissions, and ensuring compliance. PV physicians' work in HAs mainly involves guidance, assessing applications submitted by the pharma companies, and taking decisions in the interests of patient safety in a particular country. CROs also play an important role in providing support to individual tasks of a larger company PV department.
Increasingly, PV is becoming an important aspect of early phase drug development, and drug safety regulations are well in place once a medicine is licensed. It is important for companies to bring in PV colleagues earlier in the process of drug development; ensuring appropriate safety requirements are met with and considered for risk management. The concept of drug safety has changed overtime, and it has become more of a B-R assessment which is conducted on an ongoing basis of a drug life cycle. This concept of B-R acceptability can vary according to a therapeutic area and medical need of a drug. A good example may be an oncology orphan drug versus a mature established drug such as paracetamol where disease epidemiology, patient survival, and alternative treatment options may play a significant role in the decision making of B-R assessment and license approval or renewal of a particular drug.
There are challenges within PV such as thorough evaluation of available data, identifying the appropriate B-R balance, taking decisions in the interests of patient safety, timely communication, and follow-up. There are also challenges in form of the lengthy process of drug development, costs, resources, changing regulatory landscape, and low reporting of AEs by HCPs. More efforts are being made to encourage patient reporting of AEs. Social media is playing an important role in today's lives, and there needs to be a strategy to capture this useful information while disregarding background "noise."
Overall, the science of PV has come a long way since the thalidomide disaster in 1960s and regulations around drug safety have been evolving. The scope of PV has increased and emerging markets constitute an important component of GPV now. This is both in form of outsourcing cost efficiencies and more PV regulations around selling drugs in these rapidly growing emerging markets. This is leading to an interesting expansion of PV and rewarding experience of improving healthcare of patients around the world. More needs to be done to identify better strategies for collaboration, partnerships, harmonization, and taking this discipline forward in the interests of patients. Pharmacogenetics and personalized medicines are also work in progress to reduce the incidence of adverse drug reactions and make drugs more effective in individual patients. Keeping everything in mind, the future of PV seems more attractive, worthwhile, and important in pharmaceutical science which will go a long way for improving health of patients and use of medicines. Input by, to, and for the cardiologist remains important to manage the safety of patients taking medicinal products.
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Conflicts of interest
There are no conflicts of interest.