Proposed Adr Monitoring Model Health And Social Care Essay

Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal- 576 104, India.

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Overseeing the conduct of clinical trials and monitoring adverse reactions to drugs are important mechanisms for assessing the safety and efficacy of pharmaceutical products. The former helps to ensure the integrity of research design and protect trial subjects from potential harm from new drugs. The latter is an essential form of post-marketing surveillance for drugs already in the market. As Adverse drug reactions (ADRs) are also a major problem and have significant economic impact on healthcare systems. More than 50% of approved drugs were associated with some type of adverse effect not detected prior to approval. The existence and operation of these two mechanisms are important components of drug regulation and reflect the authority’s ability to regulate the entire process of pharmaceutical product assessment. In this article we are comparing the status of ADR monitoring system between different countries that is Ghana, New Zealand, Saudi Arabia, Tanzania, Iran, Thailand, and Peru.

Proposed ADR monitoring model.

The model is based on an, Input Process Output framework. It basically addresses the following components of monitoring of ADR:

Inputs: how an ADR monitoring system acquires necessary information; who reports ADRs; whether reporting is voluntary or mandatory

Process: how ADR reports are handled; whether reports are validated; whether there is an expert committee to carry out validation

Outputs: what happens after the analysis; whether information from the review is fed back to the reporters; which parties receive the information; the kind of regulatory actions taken, if any, as a result of ADR review

Keywords: Adverse drug reaction, WHO, Uganda, Ghana, New Zealand, Tanzania, Saudi Arabia, Iran, Peru, Thailand.


Overseeing the conduct of clinical trials and monitoring adverse reactions to drugs are important mechanisms for assessing the safety and efficacy of pharmaceutical products. The former helps to ensure the integrity of research design and protect trial subjects from potential harm from new drugs. The latter is an essential form of post-marketing surveillance for drugs already on the market. The existence and operation of these two mechanisms are important components of drug regulation and reflect the authority’s ability to regulate the entire process of pharmaceutical product assessment [1]. This study examines ADR monitoring systems in the 8 countries. The criteria for the selection of countries included existence of a national MRA, Guidance and regulation procedure given by the MRA, variability in medicine regulation, production or import of the medicine in the country, type of government ⎯ federal or unitary; Developed country/middle-income or low-income developing country/newly independent country. An ADR monitoring model, as depicted in figure 1, was taken as reference form "effective drug regulation"for the analysis.

ADR monitoring model

The model is based on an input-process-output framework. It basically addresses the following components of monitoring of ADR:

Inputs: how an ADR monitoring system acquires necessary information; who reports ADRs; whether reporting is voluntary or mandatory

Process: how ADR reports are handled; whether reports are validated; whether there is an expert committee to carry out validation

Outputs: what happens after the analysis; whether information from the review is fed back to the reporters; which parties receive the information; the kind of regulatory actions taken, if any, as a result of ADR review.

adr reporting model

Figure 1: ADR reporting model [1]

Information on drug reactions is the main input into the ADR monitoring system. Source of information are:

Health professionals — particularly physicians and pharmacists.

The marketing authorization holder, who possesses information on the ingredients of a product and the processes of manufacturing, packaging, storage and distribution, is another key source.

Multinational corporations having mechanisms for collecting information on the use of their products in the countries where they are marketed.

Consumers - Important source of information, since they experience any adverse effects at first hand.

ADR reporting may be either voluntary or obligatory. Spontaneous reporting by health professionals is often favored, since it is very difficult to make reporting compulsory. But in many countries, considerations of ethical responsibility and/or technical expediency have inclined governments to make reporting mandatory for the holders of marketing authorizations. The next element is processing ADR reports. Generally the ADR reports are sent to a single organization. The way the reports are handled there determines how effectively and fully the information will be used. Tracing and following up the incidents and identifying whether there is evidence for the effects of the drug in question helps to validate the information and establish the epidemiological pattern of adverse reactions. The flow of ADR information should be a loop rather than one-way. If the problem is confirmed, regulatory action should be considered where applicable, and where deemed useful in preventing potential harm. [1] The ability of an ADR monitoring system to help prevent drug-induced injury depends on three factors:

There must be a high probability that potential adverse drug effects will be identified and reported

Reports must be reviewed and validated by experts

Review results must be fed back to the relevant parties and appropriate regulatory action must be taken.



As compared to the other countries in Africa Uganda lags behind in the adverse drug reaction reporting program. According to National Drug Authority, Uganda, there are still various delays in the ADRs reporting system in Uganda, because the current system of Reporting ADRs in Uganda is paper based spontaneous reporting, this is rather as low system, uses a lot of human labour, does not enforce confidentiality and security of information.[2]

In Uganda ADR reporting system currently carried out in following ways:

Spontaneous reporting:

A system whereby case reports of adverse drugs events are voluntarily submitted by health professional and pharmaceutical companies to national pharmacovigilance centre. [3]

Uganda pharmacovigilance Centre:

Uganda pharmacovigilance centre located in the drug information department at National Drug Authority (NDA). The main function of the centre is to collect, analyse and evaluate adverse drug reaction reports from fields of the human and veterinary drugs; Promote and exchange of the drug information with the DICs (Drug Information centre) within and outside the country; collaborates with WHO other drug monitoring centres NDA.[4]


Figure 2: Loopholes of the undeveloped ADR monitoring system in the Uganda.

The head of Drug Information Department (DID) reports to the executive secretary/ registrar (ES/R) of the NDA, who in turn reports to the chairman of the board, who reports to the minister of health. The national centre for PV was established in the Drug Information Department (DID) at NDA. DID is one of the 5 core departments of NDA. Apart from the head of DID, there is a Drug Information pharmacist, 2 drug information technicians (nurse, pharmacy diploma) who handle PV activities. There is also a PV Advisory Committee of the NDA Board which is the strategic and decision making arm of the NDA [2]. In Uganda, till more than 200 reports professionals.[2,4]

New Zealand

After release of Professor Peter Davis’s report on adverse events, in December 2001 there was an increase in awareness of various issues related to patient safety. [5] The Centre for Adverse Reactions Monitoring (CARM) in Dunedin is New Zealand's national monitoring centre for adverse reactions. It collects and evaluates spontaneous reports of adverse reactions to medicines, vaccines, herbal products and dietary supplements from health professionals in New Zealand. Currently the CARM database holds over 50 000 reports and provides New Zealand-specific information on adverse reactions to these products, and serves to support clinical decision making when unusual symptoms are thought to be therapy related. [6, 7]

CARM (Center for adverse research monitoring) produces the highest rate of reporting ADRs in the world, both in terms of reports per 1000 doctors and reports per million population (New Zealand Pharmacovigilance Centre 2004), having national programs as the only source of information on ADR trends does not allow individual healthcare organizations, such as hospitals, to analyze the contribution of drug-induced illness to the morbidity, mortality, length of stay of patients, and the overall healthcare costs of the individual organization.[8]


Data management group

Clinical evaluation and casualty assessment

CARM Database

Clinical evaluation and casualty assessment

Reports priority

All medicine

CARM ADR report card

Child immunized with MeNZBTM

Pharmacy Prescription data

Health care professionals, coroners, consumers and Pharmaceutical companies


Medicine adverse reaction committee

Safety review and data analysis

Clinical evaluation and casualty assessment





Selected marketed medicine

Figure 3: ADR monitoring model in New Zealand [7] IMMP: Intensive Medicines Monitoring Programme; IVMP: Intensive Vaccine Monitoring Programme;

CARM as New Zealand's national monitoring centre, collaborates with and pools anonymised data, together with other national monitoring centres, into the database of the World Health Organisation's International Drug Monitoring Programme based in Uppsala, Sweden. Through this network, New Zealand is able to keep abreast of the latest concerns around drug safety as they emerge, whilst access to the international database servers to complement the local experience of adverse reactions to medicines. [6]

CARM undertakes regular analysis of the database to identify any significant patterns of adverse reactions and the results may suggest that relevant prescibing advice should be emphasised or changed.[9] These results are considered by the Medicines Adverse Reactions Committee. This government appointed committee makes recommendations to MedSafe which has the responsibility for implementing strategies that should result in the safer use of the medicines concerned.

The Intensive Medicines Monitoring Programme undertakes prospective, observational, cohort studies on selected new medicines. [10] These are aimed at measuring the incidence of adverse reactions, their characterisation, and the early identification of previously unrecognised reactions and the construction of a risk profile for each medicine. The results are reported to the Ministry of Health and the health professions. It has a considerable international reputation. [11]

Saudi Arabia

In 1998, the MOH in Saudi Arabia established post marketing program that aims at early detection of unexpected and serious ADR, detection of any increase in frequency of known ADR, detection of quality defect of registered products and to publish and disseminate reports regarding ADR. Training program was carried out with cooperation of the United States Food and Drug Administration (FDA) in the main regions of Saudi Arabia. The program was announced in the main hospitals and private community pharmacies and ADR reporting form was distributed to these institutions. In addition, Database for recording and storing ADR received was constructed and an advisory committee was established to study and classify the ADR reports. [12]

The Mission of the National Pharmacovigilance Center (NPC) is to contribute in protection of public health through monitoring the safety and quality medicine to ensure healthcare professionals and patient have access up to date safety information about the medicine.[13, 14]

Invalid Report


Input of ADR information by MAH, Pharmacist, Doctor and Public

No information

Further information request

Quality defect report

Data entry by pharmacist

Checking information by pharmacist

Inspectorate department


Sample Collection and analysis


Data capture by Pharmacist

Acknowledgement letter generation

Registration department

QA and Committee

Missing or incomplete information

Action Taken

Ex. Package insert change, Drug withdrawal etc.

Registration department

Warning Letter

ADR signal detection

ADR assessment

Warning letter

Figure 4: ADR monitoring model of NPC Saudi Arabia [13]

The main task of NPC is to provide information on the risk of drugs. For that purpose, NPC detects new signals through its database. Signals are discussed with Pharmacovigilance Advisory Committee in order to make the accurate decisions. The NPC has developed different ways of reporting ADRs and drug quality defects such as phone, fax, e-mail, pre-paid paper and web-based reporting forms to facilitate reporting by healthcare professionals and patients.[13]


Tanzania Food and Drug Authority (TFDA) outlined the origin of the country’s Pharmacovigilance (PV) system, followed by its current developments, weaknesses, and challenges. The national PV system in Tanzania was first established in 1989 as a drug information center (DIC), known as the Tanzania Drug and Toxicology Information Services (TADATIS), in Muhimbili National Hospital. Among the key functions of TADATIS were promoting, reporting, and analyzing ADRs, with reports submitted to the World Health Organization (WHO). In addition, it also provided pharmaceutical information and education for the public and health care workers about rational use and prescribing through radio, TV, bulletins, and newspapers. In 1998, TADATIS was incorporated into the Ministry of Health (MOH) to be part of TFDA, where a risk analysis section (for PV) was established under the Directorate of Inspection and Surveillance. At the lower level, TFDA has since established four zonal drug information centers (ZDICs) in Dar es Salaam (Muhimbili), Bugando, Mbeya, and Kilimanjaro. In July 2003 Pharmacovigilance Department is converted into ‘Risk Assessment and Product Promotion Control’ and was activated from July 2004 and again renamed Pharmacovigilance and Clinical Trial Control Department. [15]

Tanzania has some good systems in place and has been collecting ADR forms and entering some of them into UMC’s Vigiflow software. The information is mostly reported by medical doctors and medical assistants and sent to the centre through their regional centres of health.[2]

Monitoring Adverse Drug Reactions in Southern Tanzania (CDC/IHDRC)[15]:

Centers of Disease Control and Prevention (CDC)/ Ifakara Health and Development Research Center (IHDRC) presented their work under the Intermittent Preventive Treatment in infants, or IPTi initiative, which examines the use of sulfadoxine-pyrimethamine (SP) in the Lindi and Mtwara regions. Their activities centered around two reporting-related components—

Yellow card system—design, training, follow-up, and reports

Linked database approach

In Tanzania, till now 900 reports have been collected since the inception of the program, with 217 reports collected between June 2006 and July 2007.[2] Once report received then it has been send to various department and report is to be reviewed within 5 days. (in the case of emergencies they are attended to upon arrival). The priority objectives for the department are to

Promote health providers’ responsibility to report ADRs, and

Sensitize patients to also report ADRs, although there is no process for recording ADRs from patients directly

The system uses Vigiflow and is linked to UMC. So far only 67 ADR reports were entered into Vigiflow, in the e2b format, and another 580 ADR reports were entered into Vigibase (the older format).[2]


The National Pharmacovigilance Center in Ghana was established in 1998 and became part of the WHO program for International Drug Monitoring in 2001.[15] It is currently located within Department of Clinical Pharmacology & Therapeutics, University of Ghana Medical School.[16] The center promotes ADR reporting through—

Distribution of ADR forms to institutions, with proper training

Use of mass media—TV/radio programs, newspapers; includes training of reporters to ensure that pharmaceutical safety information is accurately reported to avoid public.[15]

Food and Drug Board (FDB), Ghana has set up a structure for the monitoring of the adverse drug reaction by nominating zonal or regional offices and institutional contact person in all health institution. Main responsibility of institutional contact person to report zonal officer or safety monitoring unit or national pharmacovigilance centre of the board. While zonal officer or regional officer should report to chief executive of the board.

After all this process, board will appoint the committee including health professional, scientific society, academic person and government person.


The Adverse Drug Reaction Monitoring Center (ADRMC) in Iran started its activities as a full member of WHO International Drug Monitoring Program in 1998. Studies shows that total 17967 reports of adverse events have been registered in ADRMC out of which 1094 reports was characterized as medical errors ceftriaxone and tramadol are most frequent medicine reported as suspected drug. Till now, 86 safety alerts have been issued by ADRMC. ADRMC also collected some data from yellow cards and international information center which is important make change in the labeling information. Studies say that, there are 30 safety labeling changes for medicinal products based on ADRMC assessments. Finally due to severe adverse drug reactions, 23 products have been recalled by ADRMC and four drugs i.e., terfinadin, phenylpropalonamine, iron dextran and cispride suspension have been withdrawal from market.[17]


In Peru, pharmacovigilance system started in 1999 by Ministry of health, Peru. National Center for pharmacovigilance (Centro Nacional de Farmacovigilancia) is organization responsible for the regulation of the adverse drug reaction monitoring. Source of ADR information is drug stores, pharmacy colleges, health universities, network social security health services, network public health services, medical societies, prescriber and dispensers. Health ministry of Peru also accepts information from National Health Services of Army, air force, navy and police departments. [18] This all reports then forwarded to UMC (Upasala Monitoring Center). Till first quarter of 2009, pharmacovigilance center has accepted total 16074 reports, out of which 10379 reports are obtained from health professionals, 4668 from pharmaceutical companies and 1027 reports obtained from health strategies.[19]


Ministry of Thailand started a pilot project in 1980 regarding the adverse drug reaction in certain hospitals which was belonging to Ministry of Health and two schools. Later on in the year 1983, the Ministry of public health set up the adverse drug reaction monitoring centre under the responsibility of the Food and Drug Administration. The centre collected and analysed the information on the risks and adverse reactions of drugs employing the applications of epidemiology and appropriate statistics. It also set up monitoring systems in order to detect adverse drug events. Since 1983, Adverse Drug Reaction Monitoring Center had expanded their work in affiliated hospitals in all over Thailand. The regional and country-wide system for the reporting of suspected adverse drug reactions commonly known as spontaneous reporting system is currently employed in reporting of adverse drug reactions. Till year 1992, adverse drug reaction monitoring centre had established 19 sub centre in through Thailand which is up to 23 till now.[20, 21]

If there were incidences or outbreaks related to the products which directly affect the consumers, the responsible divisions of the Food and Drug Administration in collaboration with the Epidemiological Division, Office of the Permanent Secretary of Public Health will investigate and search for more information. After the investigation has been completed, the report will be sent to the responsible agencies for acknowledging the facts and distribute the information further. The work formats in different hospitals may vary according to the availability of personnel, administration and other related issues. The large hospitals or hospitals with high potential may be able to operate in both active and passive manners; whereas the small hospitals or hospitals lacking of resources may play only passive roles. [20]

Active APRM is method performed by having a health team participating in inpatient care with respect to pharmaceutical treatments. One of their activities is to monitor adverse product reactions. After detecting an APR, the information will be recorded and determined for degree of probable relationship to the particular products according to the criteria of causality assessment. These reports will be sent to corresponding regional APRMC (within the hospital) in order to be computed, evaluated and sent to the national APRMC at the Food and Drug Administration. [20]

Passive APRM is the monitoring system by which reports of APR obtained from the physicians and nurses will be sending to the hospital APRMC. The personnel from such center will collaborate with the nearest pharmacist or Satellite Pharmacy Units in order to follow up and record in the APR reporting forms together with causality assessment. The reports will be sent to the regional APRMC for filing in the computer and passed on to the National APRMC at the Food and Drug Administration.[20]

Number of reports from the past performance the numbers of reports gradually increased from 200 reports in 1983 to 14,000 reports in 2003.[21]


It is our hope that, this review will provide an easy quick overview for comparing status of adverse drug reaction monitoring and pharmacovigilance in selected countries. It will also useful for the quick reference of the regional or scientific philosophy on their applicability. Pharmacovigilance is broad concept, and includes regional evaluation of marketed drugs, risk management, communication, and promotion of rationale use of drugs. Hence it is very important to provide training in all of related activity areas.

We caution that the regulatory landscape is dynamic, and this review is no substitute for consultation with the full text of currently applicable guidance and regulations.

It is further hoped that continued research and scientific/regulatory dialog might lead to optimal and harmonized application of adverse drug reaction reporting in the interest of improved worldwide safety and efficacy of essential medicines.