INTRODUCTION:

Drug event monitoring is a method of active pharmacovigilance. Active surveillance can be achieved by reviewing medical records or interviewing patients and / or physicians to ensure complete and accurate data on adverse event. Hospital – based adverse event monitoring is one of the systems used to collect data on drug prescriptions and adverse event. In this method, trained health personnel monitor patients admitted to selected hospital by reviewing their clinical charts and conducting structured interviews of both patients and physicians. Information on patients demographics, indication for the treatment, duration of therapy (including start dates), dosage, clinical events and reasons for discontinuation can be included in case record form^1,
2. Adverse drug reactions and adverse drug events are a common clinical problem especially in hospitals since all medical products entail an inherent risk³.

In India intensive event monitoring programme has been used for the adverse event monitoring where the pharmacovigilance officer used to collect the adverse event from the various department of the hospital. He has to communicate to the physician of the respective units regarding the adverse event. The system has many lacunas for reporting the adverse event as fear of personal and organizational liability, labor-intensive, complex, and time-consuming reporting processes, minimal feedback provided to reporters, no incentives, rewards, or motivation to report. These systems are characterized, however, by a high rate of underreporting, which varies depending on the types of ADRs and drugs in question. Educational interventions have been shown to influence reporting rates ^{4, 5, 6}.

There is no study till date which focused on the improving the IEM of the ADRs. The objective of the study was to motivate health-care providers to file adverse event reports with greater frequency and accuracy. The present study was planned to rule out the underreporting causes in the IEM and interventional improvement in the same.

AIM AND OBJECTIVE:

To assess the effect of the training on drug safety monitoring (quality and quantity of ADR reporting) in the IEM.

METHODOLOGY: -

The study was conducted in tertiary health care centre, Nashik for the duration of ten (10) months after approval of Institutional Ethics Committee and was divided in to two parts Part A and Part B.

Part A: This is the routinely used method for the intensive event monitoring. In this method daily rounds in IPD and OPD of Internal Medicine, Pediatrics, Skin, Ophthalmology, and General Surgery was taken and consulted for any Adverse Drug Events occurrence in patients with their respective physician. After finding any adverse event (as told by Physician) the investigator was approached the patient and document his/her demographics, the name of suspected drug/s, type of reaction, time of onset, whether adverse reaction subsided or not, all concomitant medicines and history of any allergy. Study participants were see whether drug is de-challenged/ re-challenged or not. Quality of the report was assessed according the Individual Case Safety Report, WHO Uppsala. The quality assessment scale contain 16 parts, according to the score was given. The outcome of the system was measured by the measuring the frequency and accuracy. The study was performed for three month.

Part B: In part B the same department participated for the IEM programme but here we ruled out the causes of underreporting as observed in part A (Internal Medicine, Pediatrics, Skin, Ophthalmology, and General Surgery) the data on all patients suffered from the adverse event were collected by pharmacovigilance officer trained by our team and validated by the expert panel of pharmacologist, clinicians. Part B of the study was performed for the 7 month of the duration for assessing the effect of the training. Interactive educational intervention was designed to increase physician awareness of ADRs and to facilitate the transfer of knowledge into physicians' everyday routines. The educational intervention was divided into a theoretical and a practical part. The theoretical part consisted of a presentation on the economic and epidemiological importance of ADRs, as well as on the definition and classification of ADRs (i.e. in terms of seriousness, severity, and causality). The practical part of the intervention included a problem-based learning course that provided practical examples of how to document ADR using the Central Frug Standard Control Organization ADR reporting form. They were practically trained for the causality, severity, and the preventability assessment. Physicians were instructed to report all ADRs, including those that were mild or anticipated.

The underreporting cause for the study A was ruled out in the following manner

Fear of personal and organizational liability: The trained medical professional communicated with not only physician but also with the nurses, registrar, and resident medical officer of the respected unit and explained the importance of the adverse event reporting.

Labor-intensive, complex, and time-consuming reporting processes: The process made simple by helping out to participants (physician, nurses, registrar, and resident medical officer) as the making simple way for filing the ADR form. Assistance provided to participants at the initial stage until they become independent. So that the participants have easy process rather than the complexity and time consuming.

Feedback provided to reporters: The constant feedback was provided at the every week regarding the number of AE reported by the concern department. Information about the seriousness, causality, severity, expectedness of the ADR provided to the participants.

No incentives, rewards, or motivation to report: Importance of the voluntary reporting and importance of the AE reporting to the India was explained to the participants.

The following information was recorded on Case Record Form: Patient Demographics (Age, Sex, body weight, height, race, and pregnancy) anamnestic dada (drug history, physical illness, alcohol consumption, nicotine or drug abuse and previous ADR, currently administered drug (dose, timing and route of administration) manifestation thought to be ADR, including the timing of onset and ending, implicated drug, severity, and predisposing factor. All suspected ADRs were filled in ADE form designed by CDSCO for the National Pharmacovigilance Programme. All dada were inserted in a database (Microsoft excel) and analyzed. The ADE was assessed for causality ¹⁶and severity ⁷. After causality assessment of all ADRs was studied for preventability ¹ i.e. to check whether the ADRs are preventable or not. The seriousness of the ADRs was assessed as per WHO guidelines i.e. to see whether ADR results in death or is life threatening or requires hospitalization or prolongs hospitalization or results in significant disability.

Direct impact of attitudinal improvement, ADR reporting quality of information was assessed on the intensive event monitoring system on the health care professional.

Data Collection: During the study period, the participating physicians continued to follow their routine documentation procedures, recording diagnoses and prescriptions for each consecutive patient.

Monitoring Programme: All ADR reports were monitored by the study centre and checked for completeness (i.e. data provided for all obligatory items plausibility, association in time between drug administration and ADR). Classification of ADR seriousness and severity according to ICH and WHO-ART criteria. Assessment of causality according to WHO- UMC criteria. To assess the quality of reports, the study centre performed its own assessment of reported ADRs according to Common Terminology Criteria For Adverse Events criteria. These steps took place independently of the participating physicians. The study centre phoned the physicians to confirm that their reports had been received and asked them to supply any missing data. Also The 24 hour contact number was provided to report ADR. Once telephone call received pharmacovigilance officer (investigator) visit to the concerned department for the ADE data collection. Feedback for the reported ADRs was provided. The participant also encouraged by the letter of appreciation for the ADR reporting. The whole data collection period lasted for 10 months (three month before the study and seven month after the study).

Statistical analysis: To measure changes in the ADR reporting rate, the median number of ADR reports and Interquartile Range (IQR) were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Fisher’s Exact Test was used for categorical data (i.e. data on ADR completeness). The level of statistical significance was set at P < 0.05. All the analysis was performed in the Graph pad Prism version 5.00.

Inclusion criteria: -

1) Patient from any age group.

2)Patients from OPD of Internal Medicine, Pediatrics, Skin, Ophthalmology, and General Surgery

3) Patients from IPD of Internal Medicine, Pediatrics, Skin, Ophthalmology, and General Surgery.

Exclusion Criteria: Patients unable to give the written informed consent.

FLOWCHART (Methodology)

Flow Chart: Evaluation

RESULTS: -

Total 531 ADRs were reported during the study period. The ADR reporting in the IEM was less before the intervention, only the 31 (5.83 %) of ADR reported in the same phase. As the intervention started there was significant increase in the ADR (94.16 %) reporting by the hospital doctors to the investigator. (Graph No: 1)

Graph No. 1. 1: Effect of the intervention training on the ADR reporting in Intensive Event Monitoring

Majority of the responders were unaware (29, 80.55 %) about the intensive event monitoring system only few doctors (8, 22.2 %) were aware about the same. Many of them agree (22 (61.11 %)) that they don’t have the time for the ADR reporting. (26,72.22 %) doctors were agree that lack of time to communicate or discuss with the pharmacovigilance officer or pharmacologist when he visit to the department for ADR information is the main barrier we found in the intensive event reporting. Position level in the practice is found to be the major barrier in the participating to the ADR reporting and 22 (61.11 %) doctors were agree to same. The causality analysis is the important factor in the ADR reporting and its found that 30/36 (83.33 %) doctors were unable to perform the causality analysis. Table No 2 provides the more details about the observations. (Table No 1.1)

Completeness of the ADR reporting from is obligatory items on the ADR reports, including information on all current medication, current diagnoses, and description of ADRs increased from 22.14 % before to 52.56 % after the educational intervention. The largest improvement was seen for the patient demographic parts, suspected medication part and the causality analysis nil to 187 (P< 0.001) after the intervention. Similarly, the completeness of the sub-item 'Date drug stopped' increased from 62.0% to 85.1% (P < 0.001). Although no improvement was seen for the sub-item 'Diagnosis name', this item was already complete on 96.6% of the ADR reports filed before the intervention. Finally, a statistically significant increase was observed in the completeness of the sub-item 'Serious or non-serious according to ICH' after the intervention (P < 0.001). Table 3 provides a more detailed overview of the changes in the completeness of these important items. (Table No 1.2)

To evaluate the quality of ADR reports, inter- reliability between the physicians' and the study centre's classification of ADRs according to ICH criteria, as well as between the physicians' and the study centre's assessment of causality according to UMC criteria was calculated. There were no considerable changes in the quality of classification according to Naranjos and WHO criteria after the educational intervention. Table 1. 3 provide a detailed overview of the changes in physicians' assessment of seriousness, severity, and causality according to Naranjos, WHO- UMC criteria, respectively. Physicians assessed causality as certain in 2.8 % of the ADR reports before the intervention, but as probable in 42.2 % and possible in 35.5 % of the reports after the intervention. Only 17.7% of the reports filed after the intervention included a causality assessment of certain. (Table 1. 3)

Average age of the participant was 36 (SD ± 6.1) years and 60% were male. Of the participating doctors, 19.44 % were consultants, 33.33 % (12) were residents, 25% (9) were interns, and 22.22 % (8) were junior residents. A total 587 ADRs were reported during the study period. 31 ADR were before starting the study and 556 ADR after the intervention indicated significant increase in the improvement and the success of the intervention (Table no 1.4)

Table No 1. 1: Barriers for the Intensive Event Monitoring

Barriers	Agree	Disagree
Non-Awareness of the Pharmacovigilance System (Intensive Event Monitoring)	29 (80. 55 %)	8 (22.2 %)
Lack of time to fill in a report	22 (61.11 %)	14 (38.88 %)
Lack of time to communicate / discuss with the pharmacovigilance officer or pharmacologist about the ADR	26 (72.22 %)	10 (27.77 %)
Single report may affect the ADR database	15 (41.66 %)	21 (58.33 %)
Lack of time to actively look for an ADR while at work	17 (47.22 %)	19 (52.77 %)
Don’t feel the need to report	12 (33.33 %)	24 (66.66 %)
Not able to perform causality analysis	30 (83.33 %)	6 (16.66 %)
Position /level in the practice is the barrier in the ADR reporting	22 (61.11 %)	14 (38.88 %)
Fear that if ADR reported that generate the extra work	16 (44.44 %)	20 (55.55 %)

N = 36 responders

Table No 1. 2: Completeness of Obligatory Items on Adverse Drug Reaction (ADR) Reports

ADR Report	Before Educational Intervention		After Educational Intervention		P Value
ADR Report	(n) (31)	% 100%	(n) (500)	% 100%
A. Patient Information 1. Patient identifier Initiales	5	16	303	60	0.0040*
2. Age at time of event:	12	38	409	81.8	0.0283*
3. Date of Birth:	3	9.67	250	50	0.0022*
4. Sex	5	16	368	73.6	0.0004*
5. Weight (Kgs)	1	3.2	167	33.3	0.0024*
B. Suspected Adverse Reaction 1. Date of reaction started (dd/mm/yy)	13	41.93	289	57.8	0.4211
2. Date of recovery (dd/mm/yy):	1	3.2	109	21.8	0.026*
3. Describe reaction or Problem	9	29	379	75.8	0.0131*
3. 4. Name of Reaction	21	67.74	445	89	0.3928
C. Suspected medication(s) 1. Name (brand and / or generic name)	24	77.41	419	83.8	0.8893
1.Dose used	5	16	210	42	0.057
2. Route used	8	25.80	311	62.2	0.027*
3. Frequency	9	29.00	326	65.2	0.0351*
4. Date started	7	22.58	315	63	0.0154*
5. Date stopped	2	6.45	217	43.4	0.014*
6. Reason for Use or prescribed for	3	9.67	312	62.4	0.0002*
7. Treatment of ADR Completed	3	9.67	168	33.6	0.0381*
8. Causality	Nil	Nil	187	37.4	<0.0001*

* Significance (Fisher’s Exact Test)

Table No 1.3: Effect of Intervention on Causality, Seriousness and Preventability of ADR Reports Before and After the Training

Sr. No.	Before Intervention (n= 31)	After Intervention (n= 500)	‘P’ Value	Experts Quality Assessment
Causality
Certain	0 (o %)	14 (2.8 %)	1.00	16
Probable	10 (32 %)	211 (42.2 %)	0.597	197
Possible	09 (29.03 %)	175 (35%)	0.7129	193
Unlikely	03 (9.63 %)	46 (9.2 %)	0.9354	35
Unclassified	06 (19.35%)	26 (5.2%)	0.0134*	36
Unclassifiable	03 (9.63 %)	28 (5.6 %)	0.4237	23
CTCAE Classification
Grade I(Mild)	17 (54.83 %)	311 (62.2 %)	0.7609
Grade II (Moderate)	07 (22.58 %)	123 (24.6 %)	1.00
Grade III (Severe)	6 (19.35%)	45 (9 %)	0.123
Grade IV (Life Thretening)	2 (6.45 %)	19 (3.8 %)	0.3615
Grade V(Death)	Nil	2 ( 0.4 %)	1.00
Seriousness
Serious	8	66	0.1248	78
Non-Serious	24	479	0.4897	422
Preventability
Definitely Preventable	22	379	0.8869	342
Probably Preventable	09	121	0.6861	158

*Significant (Fisher’s Exact Test)

Table No 1.4: Demographics and Characteristics Features Of the Responders Participants:

Characteristics	Value
Median Age (years)	31
Median year of practice (years)	4
Male: Female Ratio	21:15
Consultants	7 (19.44 %)
Residents	12 (33.33 %)
Interns	9 (25%)
Junior Residents	8 (22.22)

DISCUSSION:

The study showed significant increase in the quality and quantity in the intensive event monitoring after the intervention. Previous part of this study has shown inadequate knowledge of doctors about ADRs and reporting before the intervention similar to the previous reports among the resident doctors in Nigeria ⁸, and doctors in many countries across Europe ^9,10,11, America ^{12, 13} and Asia ^{14, 15}. Unawareness of the pharmacovigilance system is the major reason for this, even at initial phase the terminologies like Adverse Drug Reactions was difficult to understood to the participants. The terminology as “toxicity” was the favorite among the doctors and considered as the adverse drug reaction. There is no undergraduate training in pharmacovigilance and medicine risk perception in India may be insufficient or improperly delivered to prepare the doctors for the dug safety monitoring. In this study many factors influenced the underreporting mechanism for the IEM like other countries around the world. Ignorance (not feel the need to report well recognized reaction), difference (concern that the ADR report may wrong) and indifference (lack of time to fill in a report) significantly influence the underreporting the cause.

Significant increase both in the quantity and quality of ADR reports was observed after physicians took part in the intervention. This finding indicates that the intervention increased physicians' awareness of ADRs and that the physicians were able to transfer. The knowledge they had gained from face-to-face training into their everyday clinical practice. The impact of the intervention, however, was temporary. As the observations showing that once we introduced the training and education within next three to four months there was significant increase in the quality and quantity of the ADR but following the later month the pick was not maintained at the constant rate. Similar results were found by Figueiras et al, who examined the effectiveness of educational outreach visits for improving ADR reporting by physicians. The maximal effect in their study was observed during the first four months after the intervention, and the differences remained statistically significant for 12 months ⁴. Bracchi et al. found that training improved the rate and quality of ADR reporting, but the effect was also of only short duration ⁵. In the second phase the maximum stress was on the causality assessment as this part was the difficult according to the participants. The most confusing was the WHO causality assessment scale. Naranjos algorithm is the most preferred for the causality assessment. This study also shows that doctors are willing to improve the knowledge about the ADR reporting. The interest was shown maximum by the interents, and the new residence, however the reporting rate is maximum in the younger generation health care professionals vice versa it was declining with the age. The position / level in the field and the seniority may be the reason for this observation.

Monitoring and documenting of ADRs are crucial to encourage and to ensure safe use of pharmacological agent. Hospitals are required to monitor routinely for adverse drug experience, including preventable and non-preventable ADRs, and to report all ADRs that result in a sentinel event. The lacuna of the present study is the decline in the reporting at the end indicating the decrease interest in the reporting. This also indicates the Continuous Medical Education (CME), training session, workshops and conferences on pharmacovigilance depending on the need by the regulatory authority.

CONCLUSION:

The intensive Event Monitoring is the important method for the pharmacovigilance; the system can be successful with improved training in the pharmacovigilance and risk perception of drugs. The interest of the health care professionals needs to maintain through the CME, Workshop and conferences on the pharmacovigilance.

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Received on 21.06.2011 Modified on 30.06.2011

Research J. Pharm. and Tech. 4(9): Sept. 2011; Page 1443-1448