Role of Therapeutic Drug Monitoring in Medication Safety, Physicians Perception, and Practice

Introduction: Patients admitted to the hospital will receive various drugs, each carrying the risk of error. Medication errors concern our healthcare system, especially considering the relatively high number of patients admitted to hospitals. Assuming that each patient receives at least two Original Research Article Alhusayni et al.; JPRI, 33(51A): 38-46, 2021; Article no.JPRI.77645 39 medications twice a day, the likelihood of a medication error is considerable. Therefore, therapeutic drug monitoring (TDM) focuses on measuring blood medication levels and plays a crucial role in medication safety. Aims: This study aimed to determine the effect of TDM in ensuring the safety of medications in many Taif hospitals. Also, to enhance the safety and quality of drug use and reflect physician perception and practice regarding TDM. Methodology: A prospective cross-sectional study consisting of questionnaires was conducted to physicians at many of Taif's governmental hospitals between March and May 2021. Questionnaires evaluated three parts: physician demographics, physician perception about TDM, and physician practices regarding TDM. The collected data were processed using the Excel program. Results: More than 80% of the interviewed physicians agreed that TDM is a tool that can guide the clinician to provide effective and safe drug therapy in the individual patient. Approximately 77% agreed that TDM is a team of decision-making groups. Around 25% of physicians performed TDM weekly, 22% monthly, and 10% daily. The medications that participating physicians ordered TDM were digoxin (30%), carbamazepine (21%), and gentamycin (17%). The participants had a limited understanding of the advantages of TDM in terms of drug safety and welfare. Conclusion: The number of actual drug errors occurs in the healthcare systems. Therefore, must establishment of TDM in hospitals. Medical administration and physicians must cooperate with the clinical pharmacist. Also, establish workshops for health practitioners to educate them about the role of TDM and pharmacokinetic laboratories in controlling the therapeutic process.


INTRODUCTION
Over the last half-century, significant progress has been made in treating various health issues, most notably infectious diseases. Unfortunately, the use of unsuitable medications to treat these conditions has resulted in significant health care problems, including increased morbidity, mortality, and prices and the development of drug resistance in recent years [1,2]. Irrational medication usage in hospitals in developing countries is a serious issue, and little research on how to address it has been published. A possible beginning point is establishing hospital-based Drug and Therapeutics Committees (DTCs) to serve as change agents [3,4]. This was one of the suggestions made during the 1997 International Conference on Improving Use of Medicines (ICIUM) held in Thailand. The advice was made in light of experiences learned from developed countries. More information regarding such committees has been released [5].
Among the additional complications associated with improper drug use include an increase in adverse drug reactions (ADR), medication errors, and the use of relatively unsafe medications [6,7]. In the United States of America, it is estimated that 10.8 % of hospital inpatients suffer from an ADR, costing between US$1.4 billion and US$4 billion annually. Adverse drug reactions are the fourth to the sixth leading cause of mortality [8]. DTC may implement processes aimed at reducing ADRs. Numerous countries currently have DTCs to solve medication selection, procurement, distribution, and usage issues and manage ongoing and developing drug concerns [9]. Most DTCs occur in developed countries, such as Australia, the United States of America, and Europe. In Australia, 92 % had established a hospital therapeutic committee. In contrast, in the United Kingdom, 86 % had established some form of hospital therapeutic committee. In the United States of America, accreditation requires the presence of DTCs or similar committees. They may also be referred to as a Pharmacy and Therapeutics Committee, a Pharmacotherapy Committee, a Formulary Committee, or a Rational Drug Use Committee in various situations [10,11].
TDM is one of the DTCs inside a hospital or primary care clinic responsible for monitoring the clinical use of pharmaceuticals, formulating drug use and administration rules, and maintaining the formulary system. TDM also provides drugrelated advice to the medical, nursing, administrative, and pharmacy departments and examines drug usage to detect possible concerns. Furthermore, it is utilized to prevent adverse drug reactions and medication mistakes [12].
TDM is a subfield of clinical chemistry that focuses on the assessment of drug concentrations in the blood. Its primary emphasis is on pharmaceuticals with a limited therapeutic range readily under-or overdosed, such as aminoglycoside antibiotics and antiepileptic medications. The efficacy of these medications is close to the threshold at which they generate severe adverse effects and/or toxicity. Nevertheless, numerous therapeutically regulated medications are prescribed indefinitely. In addition, patients may develop chronic diseases over time, such as heart disease, renal disease, thyroid disease, and liver disease. Therefore, they need monitoring medications. Since a result, TDM may play an important role in medication safety, as it can detect toxicity with any of these medications with a limited therapeutic range [13][14][15].
Until writing, no study has been done to assess the role of therapeutic drug monitoring in medication safety and assess physicians' knowledge, practice, and opinion towards TDM in Taif city. Therefore, we did this study also to know which drugs require monitoring and enhance the safety and quality of medication use.

METHODOLOGY
Prospective cross-sectional research comprising questionnaires was performed to physicians at Taif's governmental hospitals (King Abdul-Aziz Hospital, King Faisal Hospital, Prince Mansour Hospital, and AL-Hada Hospital) between March and May 2021. A convenient technique of sampling was used. Physicians aged between 30 to 60 years were recruited. The verbal informed agreement was acquired, and physicians who refused to participate in the research were excluded.
The data collection approach was a face-to-face interview with the use of a structured questionnaire. The first section of the questionnaire was meant to elicit demographic information about physicians (gender, age, nationality, and Specialty). The questionnaire's second section was aimed to elicit physicians' perceptions about TDM. The final section of the questionnaire was aimed to elicit information on physicians' TDM practices. 'Agree,' 'disagree,' and 'do not know' were used to respond to questions.
The Excel program was used to gather and analyze the data. The descriptive data were reported using frequencies and percentages.

Physician's Demographic Characteristics
One hundred physicians were included in the current study based on their demographic features. More than half (62%) were males compared to (38%) females. Physicians ranged in age from 30 to 60 years. However, 58 % of the participants were under the age of 40, more dominant than 42% were over 40, which means almost participants had a limited understanding of the advantages of TDM. Because this study was conducted in Saudi Arabia, 63% of participants were Saudis compared to 37% were Non-Saudi. The majority of physicians who participated in the research were specialists (30%) and general practitioners (27%) ( Table 1).

Physicians' Perception about TDM
According to physicians' perceptions of TDM, table 2 indicates that more than 80% of physicians interviewed agreed that TDM is a tool that can assist clinicians in providing effective and safe drug therapy to individual patients, and 77% agreed that TDM is a collaborative decisionmaking group comprised of physicians, clinical pharmacists, nurses, caseworkers, and supervisors. Additionally, roughly 88% of respondents agreed that the clinical pharmacist might play a critical role in guiding TDM collaboration services.
Of the 100 physicians questioned, only 23% agreed that TDM is limited to drug concentration monitoring. In contrast, 57% think otherwise. 86 % of physicians agreed that TDM is necessary for patients with various conditions that impact medication levels. Additionally, most physicians 67 % agreed that TDM is helpful to assess medications with a limited therapeutic index range TDM. By contrast, 9% disagreed. Approximately 44% of physicians agreed that the optimal time to sample blood from patients suspected of drug toxicity is when the symptoms are happening, whereas 41% disagreed ( Table  2).
Around the world, about 80% of samples were transmitted to a TDM service. The samples came from a variety of hospital departments and other healthcare facilities. In contrast, this is not the case in Taif hospitals, since the doctors questioned lacked proper understanding and background about the importance of TDM in drug safety.
As a result, most physicians dismiss TDM as a tool that may deliver effective and safe medication to each patient [16,17].
Hospitals and medical facilities strive to offer a tranquil healing environment for patients while also providing thorough medical treatment. However, this carries the risk of medication errors and the chance of other errors and mishaps due to enormous numbers of people continually going in and out each day. As a result, it is critical to construct TDM and pharmacokinetic monitoring labs to provide and assure a safe, confidential, and high-quality healthcare environment for medical personnel and patients [18].
Around 23% of physicians questioned think TDM is used in major organ failure, 21% think TDM is used in low therapeutic index medication, and 19% think TDM is used in therapeutic failure (Table 3). Around 34% of physicians interviewed think that TDM is critical for understanding the pharmacological and pharmacokinetic profiles of the administered drug, and 30% think that TDM is critical for determining the patient's serum or blood drug concentration at the appropriate time after drug administration ( Table  4). Tables 2-4, participants had a limited understanding of the advantages of TDM in terms of drug safety and welfare, owing to the unavailability of pharmacokinetic labs in all Taif hospitals except Alhada hospital.

As shown in
A literature review examining medication safety in Australian health care was undertaken in 2002-2008 for the Australian Commission on Safety and Quality in Health Care to build a safer medication system. These commissions are needed for better and safer medication services in Saudi hospitals and healthcare centers [19].
Digoxin, carbamazepine, and antibiotics were the main requested drugs for TDM reported by Leung et al. [20]. However, these medications are acknowledged to be dangerous and have a limited therapeutic index among doctors. This was the primary reason for forcing them to test these medications [21,22].
Approximately 31% of respondents think that gentamicin should be monitored when potential toxicity occurs: if repeated, the sample should not be less than one half-life of the previous sample, while 23% think that gentamicin should be monitored between 24 to 48 hours of treatment. 36% of participants think that digoxin should be monitored when suspected toxicity occurs: if repeated, the sample should not be less than one half-life of the previous sample. In comparison, 20% think it should be monitored for a new patient. 24 % think carbamazepine should be monitored beyond the first two to four weeks of starting medication. 25% of respondents think that phenobarbital should be monitored in the event of suspected toxicity: if repeated, the sample should not be less than one half-life of the previous sample (Table 7).  Interpretation of serum drug concentration after consideration of all above information and individualizing drug regimen according to the clinical needs of the patient Doctors were less interested in monitoring therapeutic levels at switching medicines or starting new medications. Because they think they treat people, not medicine serum levels, so they are more concerned with the patient's symptoms than the drug's blood levels.TDM requested for therapy failure and pharmaceutical side effects.
The results revealed that physicians' knowledge of TDM is fair, but further education and workshops are needed to improve physician knowledge. These should include TDM data, target medications, indications, sampling protocols, and anticipated laboratory services. Also, these TDM tests must be included in the standard authorized procedures for case management in the various specialties dealing with TDM drugs. Revision of the laboratory report data is encouraged to urge the physician to seek more TDM, especially with the introduction of medicines. Also, the correct time of TDM sampling should be considered. They may be put on TDM request forms or disseminated as a message to assist physicians inadequate sampling.

CONCLUSION
The number of actual drug errors occurs in the healthcare systems. Therefore, must establishment of TDM in hospitals. Utilizing TDM effectively needs a multidisciplinary strategy that incorporates pharmacodynamics, pharmacological and pharmacokinetic methodologies.
Physicians had a limited understanding of the advantages of TDM. Therefore must establish workshops for health practitioners to educate them about the role of TDM.
Medical administration and physicians must cooperate with the clinical pharmacist. In addition, pharmacokinetic laboratories must establish it in all hospitals to control the therapeutic process. Finally, undergraduate medical schools should consider TDM more. This should increase medical graduates' understanding and attitude about TDM.

CONSENT
Informed consent was obtained from all the participants.

ETHICAL APPROVAL
It is not applicable.