India is the fourth largest manufacturer and the second largest consumer of pharmaceuticals in the world. Hospitalizations due to adverse drug reactions (ADRs) lead to a considerable burden on the health-care system and economy of the country. Pharmacovigilance in India faces considerable hurdles due to overburdened hospitals, underreporting of ADRs, variations in reporting formats, etc. To augment ADR reporting, many countries are exploring the option of mobile- and web-based solutions. The National Coordination Centre for Pharmacovigilance Program of India, Indian Pharmacopoeia Commission has released a mobile application (app) called “ADR PvPI” to mitigate some of these issues and both standardize and enhance the reporting of ADRs. This is in line with global focus on patient-reported outcomes and real-world data in pharmacovigilance. However, this approach has many implementation challenges including lack of awareness about mobile app, the use of English language in app, low smartphone adoption among the elderly, and in rural areas.
Keywords: Adverse drug reaction, pharmacovigilance program of India, mobile application, pharmacovigilance, real-world data, spontaneous reporting
| Introduction|| |
With a population over 1.2 billion, India is the fourth largest producer of pharmaceuticals in the world and has more than 5000 licensed manufacturers and over 50,000 branded formulations in the market. Studies have revealed that adverse drug reactions (ADRs) are leading to significant health and economic burden on patients., Studies conducted in several parts of India have estimated the incidence of suspected ADRs to be nearly 2%–3% among hospitalized patients. ADRs lead to prolonged hospital stay and suffering. Therefore, drug safety monitoring has to be an essential element of health care. An ADR, as defined by the World Health Organization (WHO), is a “response to a drug that is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.” The WHO also defines pharmacovigilance as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem.” Along with drugs, the scope of pharmacovigilance also includes herbals, traditional medicines, blood and blood products, biologicals, vaccines, and now medical devices as well. It is quintessential for both the patients and health-care professionals (HCPs) to detect and report the adverse effects caused by various drugs. After getting marketing approval for a drug, pharmaceutical companies are also required to carry pharmacovigilance activity related to that drug for a stipulated time period (4 years in India). Spontaneous reporting is the most commonly used method of reporting ADRs by health professionals, and in many countries, by patients themselves. Spontaneous reporting is voluntary and involves a vigilant health professional or patient linking an adverse reaction to the use of a particular drug and reporting it to an ADR monitoring center (AMC) as individual case safety reports (ICSRs). ICSRs are ultimately sent to the WHO center in Uppsala, for processing, identification, and analysis of new signals for adverse reactions associated with particular drugs.
To this effect, the Ministry of Health and Family Welfare, Government of India, launched the Pharmacovigilance Program of India (PvPI) in the year 2010. The Indian Pharmacopoeia Commission (IPC) is the National Coordination Centre-Pharmacovigilance Program of India (NCC-PvPI) and spearheads the field of pharmacovigilance across India. Till January 2017, 250 AMCs (government and nongovernment) have been established under PvPI and report to NCC-PvPI. Currently, the contribution of India to the WHO global ICSRs database is approximately 3%.
Pharmacovigilance program in India has seen a steady progress over the past decade. India is now increasingly being recognized as a hub of global clinical trials, and a number of clinical research studies are being conducted actively. Therefore, there is an ever increasing need for a robust pharmacovigilance network that includes all the stakeholders, HCPs, and patients with an efficient yet convenient operational methodology.
| Current Challenges Being Faced by the Pharmacovigilance Program of India|| |
While PvPI heralded the structured ADRs monitoring in India, there have also been many challenges over the time. Inability of physicians to recognize ADRs in hectic clinical settings in our country and underreporting of ADRs are grave issues plaguing the pharmacovigilance system in India. Due to lack of time in routine clinical practice, clinicians have tough time properly reporting ADRs through filling ADR forms manually. Moreover; there is little to no reporting by patients due to their inability to understand the medical jargon in the current ADR reporting form issued by the NCC-PvPI. In certain cases, reporting forms used by different stakeholders to report ADRs differ greatly from the prescribed format by the PvPI, making it extremely difficult for the induction of data into the national database maintained for ADRs. Furthermore, there is a prevalence of self-medication and traditional medicines use across India, and reactions caused by them often are unidentified and unreported.
It has been recognized that technological advances made in smartphones and Internet services can be utilized to mitigate some of the above problems. The European Union's Innovative Medicines Initiative WEB-RADR (Recognizing Adverse Drug Reactions) project explored the value of two digital tools for pharmacovigilance. One of them was the use of mobile applications (apps) for reporting the adverse effects of drugs and its contribution to safety signaling. A mobile app designed for ADR reporting and product safety alerts will augment pharmacovigilance exercise and extend the reach of health authorities to patients and HCPs. While uptake and use of the apps till date seems modest in comparison with other ADR-reporting modalities, it is plausible that app-based reporting will gain traction as the current younger generation of app-literate patients matures and smartphone owners increasingly use their mobile devices to access the Internet. Multiple government-approved apps in the UK, two mobile phone apps VigiBIP (January 2015) and Yellow Card (July 2015) in France, the LAREB (January 2016) in the Netherlands, and the HALMED (May 2016) in Croatia are some of the pharmacovigilance apps already being used internationally. In accordance with the above, the NCC-PvPI has released an Android mobile app “ADR-PvPI” in 2017, which facilitates ADR reporting by both HCPs and patients. “ADR PvPI” Android mobile app for ADR reporting has been developed to have administrative control of data with IPC (NCC-PvPI). This will assist both HCPs and patients for ADR reporting with features such as the support for document and image attachment, XML, and PDF generation. This app also has separate reporting windows for HCPs and patients. Features such as autofilling of details and drop-down menus have been built in to save time.
| User Interface and Working of Mobile Application Adverse Drug Reactions Pharmacovigilance Program of India|| |
The ADR-PvPI mobile app is designed to digitize the current ADR form. On launching the app, the reporter information tab appears, having inputs such as contact information (name, phone, e-mail, and address), whether one is a patient or a HCP. There is also an option to choose preferred AMC: direct to NCC or to state monitoring centers. Next page is regarding patient information starting with patient's initials, followed by gender, age, weight, and height. This is followed by suspected adverse reaction tab, which is to be reported under headings as follows: date of reaction, date of recovery, and suspected medication/s with option to attach images and supporting documents. Further windows take inputs on “time to event relationship,” “can this reaction be explained by other drugs or disease,” “does scientific literature support the above observations,” “Remarks,” and “Seriousness of reaction and outcomes.” In case of reporter being an HCP, final two inputs of causality assessment and additional information, if any, are to be keyed in.
The reporter can download the ADR reporting app from Google Play Store™ (free to download). After filling the data subsequently in the application and submitting, two PDF files of suspected ADR form are generated. One copy goes to the reporter's e-mail account, as an acknowledgment for his/her record and for review and research purposes. The second copy goes to the AMC of reporter's choice. The AMC then uploads the same to VigiFlow™ (web-based ICSR management system), and data are sent to NCC-PvPI for further analysis [Figure 1].
|Figure 1: Adverse drug reactions reporting through adverse drug reactions pharmacovigilance program of India app: Data flowchart|
Click here to view
| Experience So Far|| |
Since the launch of the mobile app in 2017, it has been downloaded about 5500 times, and more than 250 ADRs have been reported through this app. These figures suggest low acceptance of mobile app by patients and HCPs which can be attributed to certain issues such as limited availability of Internet connectivity, low data speeds, and low smartphone usage in India, especially in rural settings. The language of the app being in English, it may not be understood by a substantial number of users. Furthermore, there is no or little understanding of medical terminology used in the app, by users who are not HCPs. Apparently, there is also possible lack of advertisement in mass media and training/awareness programs for the mobile app, leading to a low number of downloads and usage.
| Proposed Solutions to Enhance Adoption of Adverse Drug Reactions Pharmacovigilance Program of India App|| |
In a country with population more than one billion and number of health-care workers more than twenty lakhs, data suggest substantially low number of active users of the ADR PvPI app. Keeping in view of the above experience with app usage, it is clear that though it can prove to be a convenient tool for ADR reporting, certain measures need to be taken to enhance the adoption of the app. As, for example, there is a need to create awareness about this app by Continuing Medical Education programs (CMEs), mass and electronic media, and patient training sessions. The availability of the app on other mobile platforms such as iOS and support for more languages will increase its usability. The NCC-PvPI has already released ADR reporting forms in ten vernacular languages (Hindi, Tamil, Telugu, Kannada, Bengali, Gujarati, Assamese, Marathi, Oriya, and Malayalam) to minimize the language barrier in ADR reporting. Digital versions of those may be included in the app. In the ADR PvPI app, a simpler ADR form, for filling by users other than HCPs, who have little knowledge of medical jargon, may be developed. App usage is also expected to increase as smartphone usage in India becomes more affordable and Internet speeds improve.
| Conclusion|| |
An important and valuable feature of this app is that not only HCPs but also patients can themselves report ADRs. Therefore, spontaneous reporting by patients with this app will be a positive complementary contribution to the current pharmacovigilance program and will bring real data and patient perspective into consideration. Patient-reported outcomes with the convenience of reporting through mobile app will help in strengthening PvPI. This application will generate electronic health records that can be easily integrated with WHO database (VigiBase) and analyzed by VigiLyze. However, certain bottlenecks are also associated with using this app as mentioned above. As there are improvements in Internet connectivity and data speeds through ongoing telecommunication reforms, it will positively impact the app acceptance and usage. Similarly, in the app, a simpler version of ADR form and that too in multiple regional languages may be developed, for reporting by patients. To conclude, this new paradigm can coexist within the current ADR reporting system and will generate structured data in electronic form. In future scenario, this app will certainly emerge as an important complementary tool in the PvPI.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Department of Pharmacology, University College of Medical Sciences and GTB Hospital, Delhi - 110 095
Source of Support: None, Conflict of Interest: None