"ADR PvPI" Android mobile app: Report adverse drug reaction at any time anywhere in India.

BACKGROUND: To improve the public health and promote instant adverse drug reaction (ADR) reporting, a need to develop an ADR Pharmacovigilance Programme of India (PvPI) mobile app was identified by the National Coordination CentrePvPI (NCCPvPI) to serve the Pan India ADR reporting. The objective of this study was to develop an indigenous Googlebased Android mobile application known as "ADR PvPI" and to analyze the ADRrelated data reported through this mobile application on pilot basis.
MATERIALS AND METHODS: The ADR PvPI mobile application was indigenously developed by NCCPvPI officials within 6 months. The study of spontaneous ADR reporting was carried out between September 2017 and September 2018. This article provides an overview of the salient features of ADR PvPI mobile application, guides on how to fillin ADRs, reporting trends of ADR, types of ADR as per System Organ Class and pharmacological classes of drugs.
RESULTS: Till date, >5500 users have downloaded the app with an average rating of 4.26. In that tenure, 262 reports have been received through ADR PvPI mobile app. During the year 2017, 3.55% of reports were received through ADR PvPI mobile app and the percentage of reports received by 2018 was 96.45%.
CONCLUSION: The frequency of ADR reporting has significantly increased over the past 1 year and should be promoted further through awareness and training programs. Copyright:

Introduction

Adverse drug reactions (ADRs) are the major cause of morbidity and mortality.[1] Although the safety and efficacy of a drug is assessed during clinical trials, the continuous assessment after marketing authorization is necessary. To complement the drug's safety profile, postmarketing surveillance is particularly needed since descriptions of safety profile of drugs are not exhaustive and do not reflect ADRs, which occur rarely or lately after marketing authorization in real-world setting in patients consuming the drug. Hence, spontaneous reporting of ADRs has been the leading method to identify signs relating to drug safety. Spontaneous reporting of ADRs can be best explained in “pharmacovigilance” which is referred to as science and activities relating to the detection, assessment, understanding, and prevention of ADRs.[2] Spontaneous reporting of ADRs by health-care professionals is the main source of information for drug safety. However, underreporting of ADRs is the biggest challenge for the pharmacovigilance system. Spontaneous reporting of ADRs by patients is being recognized as a new source of information.[3] The patient reporting provides a detailed description of ADR with respect to type of reaction and suspected medication.[4]

The National Pharmacovigilance Centre “LAREB” in The Netherlands received 26% of all ADR reports from the patients from 2010 to 2015.[56] The Danish Medicines Agency published a report on ADR reporting by consumers and health-care professionals from 2003 to 2011, showing that reporting by consumers contributed significantly both quantitatively and qualitatively to the total number of ADRs reported.[7] In the UK's Yellow Card Scheme, patient self-reporting was investigated from 2005 to 2007, and it was found that patient reporting provides a more effective contribution to ADR reporting.[8] During the pandemic influenza vaccination campaign, the European Medicines Agency in France in 2009–2010 recommended a pharmacovigilance plan for the first time, and patients reported ADR related to pandemic vaccine directly to pharmacovigilance centers; it was revealed that no major differences were seen between patients' and health professionals' reports.[9] Earlier research has demonstrated that patient reporting may have a positive complementary contribution by identifying various drug-ADR associations and also broader information of the ADR.[810] The patient representative plays an invaluable role in ensuring the regulators to take the patient perspective into consideration. They also contribute to decisions regarding the various factors of risk communications, which play an important role in ensuring drug safety.[11]

The reports suggest that in pharmacovigilance practices, the patient participation has not been common due to concerns that patients may lack medical knowledge and would therefore probably not be able to make high-quality reports; therefore, ADR reporting was mainly reserved for health-care professionals.[12]

Access to technology has proved its significance in health-care system. There are endless users of mobile phones, and it was realized that this pervasive usage can be contextualized to deliver health-care benefit by the usage of mobile apps to report ADRs. India being a hub of pharmaceutical industry or “pharmacy of the world” with information technology capabilities made it possible to develop the mobile app for ADR reporting. The National Coordination Centre-Pharmacovigilance Programme of India (NCC-PvPI) works in the field of pharmacovigilance across India and also has been recognized as the World Health Organization Collaborating Centre for Pharmacovigilance in Public Health Programmes and Regulatory Services for Asia and beyond. NCC-PvPI has developed an indigenous advanced version of the Android mobile app “ADR PvPI” enabling all health-care professionals and consumers to instantly report ADRs. The Union Health Secretary, Shri C K Mishra, Ministry of Health and Family Welfare, Government of India, launched the above mobile app on 29 September 2017. It is a paperless, simple, user-friendly, and quickly assessed app.

Salient features of the adverse drug reaction Pharmacovigilance Programme of India mobile app

The app contains the following salient features:

Support source document and image attachment

Facilitates ADR reporting by health-care professionals as well as consumers

Facility to report at the nearby adverse event monitoring centers across India (presently, there are 270 adverse drug reaction monitoring centers (AMCs) across different states in India)

Acknowledgment to the reporter.

Methodology

A wide range of development tools are included in the Android software development kit (SDK).[13] It includes documentation, sample code, a debugger, libraries, a handset emulator based on quick emulator (QEMU), and tutorials. The document platform which supports this software includes computers running Linux (any modern desktop Linux distribution), Mac OS X 10.5.8 or later, and Windows 7.[141516]

The studio made by Google and powered by IntelliJ as of 2015 is the official integrated development environment.[17] In addition, other tools are used such as for editing Java and XML files, text editor tool is used and to create, build, and debug Android applications as well as command-line tool is used to for rebooting and installing software package remotely.[1418]

With the overall Android platform development, enhancements to Android's SDK go together. In case developers want to work in application by targeting at older devices, the SDK also supports older versions of the Android platform and SDK tools can be tested for compatibility by downloading them.[19]

The packaging of Android applications is made in. apk format and stored on the Android OS under app folder. APK package contains resource files and dexfiles.[2021]

The ADR PvPI application supports 88.4% of Android devices running on Android OS version 5.0 and higher that are compatible with Google Play [Figure 1a].

Figure 1

(a) Number of individual case safety reports received through adverse drug reaction Pharmacovigilance Programme of India mobile app. (b) Android device distribution running on Android OS

This guide provides information about the processing of adverse drug reaction in the ADR PvPI mobile app [Figure 2a and b].

Figure 2

(a) Guiding steps for processing of adverse drug reaction in adverse drug reaction Pharmacovigilance Programme of India mobile app. (b) Guiding steps for processing of adverse drug reaction in adverse drug reaction Pharmacovigilance Programme of India mobile app

Step 1: Install the app

The reporter can download the ADR PvPI mobile app from the Google Play Store free of charge.

Step 2: After installing the app, it shows three sections, namely

Reporter information

Patient information

Suspected ADR.

Note: If any field is not filled in, it will show a symbol (!).

Step 3: Reporter information

In the reporter information fill the name, phone number, e-mail, address and pincode of the person who is reporting

Then select either a consumer or a health-care professional (doctor, pharmacist, and nurse)

Then select the AMC. There are two options. One can either select the option direct to NCC (NCC or to the nearby AMC of the state to which the reporter belongs). For example, if the reporter belongs to Chandigarh, then one can select PGIMER, Chandigarh, as the monitoring center.

Step 4: Patient information

In the next step in patient information:

Write the patient initials (e.g., if the patient's name is Ram Kumar write the initials as RK)

Select the gender (male or female or other)

Mention the age (years), weight (kg), and height (cm).

Step 5: Suspected adverse drug reaction

In the suspected ADR window:

Fill the suspected adverse reaction (e.g., rash)

Write the date of reaction and date of recovery

Date of reaction: When the reaction occurred

Date of recovery: When the patient recovered from the reaction (if the patient has not recovered leave it blank).

In the suspected medication field press the green button containing sign (+) and fill the following information:

Medicine: Select if it is a single dose of drug (e.g., paracetamol) or fixed-dose combination where two or more active ingredient are mixed (e.g., amoxicillin + clavulanic acid)

Write the medicine name due to which ADR occurred

Write the dose which is used and also select the unit (e.g., mg/mcg/g/ml).

Write the name of manufacturer, batch number, and date of expiry

Select the route of drug administration used:

PO: Medicine taken orally by mouth

IV: Medicine taken by intravenous route

IM: Medicine taken by intramuscular route

S/C: Medicine taken subcutaneously

Topical: Medicine taken topically by skin

Other: Routes other than described above example by inhalation.

Write the frequency of dose used

OD: Once in a day

Bid: Twice in a day

Tid: Thrice in a day

Qid: Four times a day

Other: Other frequencies of dose used.

Write the therapy start date and therapy end date

Therapy start date: When the drug therapy was started

Therapy end date: When the therapy was ended.

Reaction abated after drug stopped or dose reduced (dechallenge): Whether the reaction was stopped after discontinuing the drug or reducing the dose of the drug

Reaction reappeared after reintroduction (rechallenge): Whether the reaction reoccurred after the drug was reintroduced. Also write the reintroduced dose.

After filling all the data, click ADD and the information would be added.

Image as attachment: If any image is available regarding the ADR, then upload the image as attachment by clicking the camera icon

Document as attachment: If any document pertaining to drug or ADR is available, then upload the document as attachment by clicking the pin icon

Time-to-event relationship: Select the relationship between the time of reaction and event which occurred

Plausible: The reaction occurred after the drug was introduced

Reasonable: The reaction occurred probably because of drug or can be due to some laboratory test abnormality or any other disease

Improbable: The reaction is not likely to occur because of drug, but it is not impossible.

Can this reaction be explained by other drugs or diseases: If the reaction is occurring not due to drug but because of any other drugs or diseases

No: If the reaction cannot be explained by other drugs or diseases

Unlikely: If the reaction is because of disease or other drugs

Could be: The reaction can be explained by other drugs or diseases

More likely: If there are instances that the reaction is because of some other drugs or diseases.

Data insufficient: If the data are insufficient to prove that reaction be explained by other drugs or diseases

Does scientific literature support this above observation: select?

Yes, if the scientific literature contains the ADR associated with the drug

Contradictory, if the scientific literature does not support the reaction.

Remarks

Concomitant medical product: Write the concomitant medication (drugs taken along with the suspected drug)

Relevant tests/laboratory data with dates: Write the test if any along with the respective dates when they are done

Other relevant histories including preexisting medical conditions: Write the medical history of any of the patients example: asthma, hypertension, and diabetes

Seriousness of reaction: Select the seriousness of reaction. A reaction is said to be serious when it occurs at any dose which results in

Death: Select if death occurs due to ADR

Life threatening: Select if it is life threatening

Hospitalization: Select if it leads to hospitalization

Disability: Select if some disability occurs

Congenital anomaly: Select if some congenital anomaly (any defect to body parts occurs during pregnancy and can be seen only after birth occurs).

Outcomes: Select the outcome of the ADR

Fatal: If it fatal to life

Continuing: If the reaction is still continuing

Recovering: If the patient is recovering from reaction

Recovered: If the patient has recovered

Unknown: If the outcome is unknown

Others: If there is any other outcome related to the drug.

Causality assessment: Assess and write the causality assessment of the drug and reaction

Additional information: Write any additional information related to the drug or ADR if not mentioned in the above fields.

Step 6: Sending the report

After all the fields have been filled in, press the envelope containing icon and send the report. As soon as the report is sent, an acknowledgment containing the following message is communicated both to the reporter and the selected center, i.e., NCC or AMC.

Step 7

The reports are further entered into VigiFlow, a web-based individual case safety report management system by the designated person, and sent to Uppsala Monitoring Centre for further processing.

Results and Discussion

Till date, there are more than 5500 downloads of ADR PvPI mobile application from Google Play Store [Figure 3b] with a cumulative rating of 4.26 on the scale of 5 [Figure 3a]. Thirty-two people have reviewed it as the most helpful app to report ADR related to a drug. An analysis of data on suspected ADRs reported through ADR PvPI Android mobile application was done up to 30 September 2018. In that tenure, 262 reports have been received through ADR PvPI mobile app, in which 20.56% reports have been reported through consumers and 79.44% reports have been received through health-care professionals [Figure 4a]. The received reports contained 59.22% of ADRs from males and 40.78% from females [Figure 4b]. During the year 2017, 3.55% of reports were received through ADR PvPI mobile app and the percentage of reports received through consumers and health-care professionals has been increased up to 96.45% [Figure 1b]. It is thus evident that ADR reporting has been increasing in this 1 year.

Figure 3

(a) Adverse drug reaction Pharmacovigilance Programme of India application cumulative rating of 4.26 in the scale of 5. (b) Adverse drug reaction Pharmacovigilance Programme of India application total downloads of over 5500 by Android devices

Figure 4

(a) Magnitude of reports received through reporters. (b) Gender-wise reporting

The ADRs received comprised mostly of nervous system disorders, followed by skin and subcutaneous tissue disorders, gastrointestinal disorders, and psychiatric disorders. The nervous system disorders mainly comprised of dizziness, drowsiness, headache, metallic taste, and sedation. Among skin and subcutaneous tissue disorders, rash, itching, and eczema were mostly reported, and in gastrointestinal disorders, mostly reported reactions were nausea, vomiting, diarrhea, abdominal pain, and dry mouth.

The drugs known to cause ADRs mostly were antibiotics such as ceftriaxone, amoxicillin, ciprofloxacin, nevirapine, cefotaxime, and azithromycin causing ADRs such as nasal mucositis, vomiting, itching in eyes, and metallic taste. Furthermore, cardiovascular system-related drugs such as metoprolol, atenolol, and amlodipine are being known to cause rashes and epigastric pain, increased coughing, and pedal edema. Anthelmintic drug metronidazole is also reported to cause metallic taste. The drugs acting on the nervous system such as diclofenac, aceclofenac, valproic acid, and chlorpromazine have been reported to cause reactions such as itching, burning, dizziness, nausea, and weight gain.

Thus, it is observed that mobile application is emerging as an important user-friendly information technology tool to consumers and health-care professionals to report ADRs.

Conclusion and Future Prospects

The mobile apps have become an essential part of daily life. In the future, this mobile application could also be compatible and available with non-Android-based system such as iOS phone. This application also has the scope of integration with smartwatches or other health-related applications so as to provide a wide range of facilities to the end user. These new approaches should bring drug safety insights faster, specific, actionable, and moving toward the target of ADR prevention. The safety of medicines cannot be assessed completely until the patients are actively involved in the practice of pharmacovigilance.

The health-care providers may educate/instruct their patients to use this mobile application in supporting the health-care system and in overall interest of patient safety.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.