The Impact of Irrational Prescription/Misuse of Drugs on Health Outcomes and its Economic Correlates

Abstract

A multi-facet study was conducted in four provinces and Capital territory of Pakistan to evaluate the perception of physicians, patients and medical store (MS) personnel regarding prescription trends, reasons of irrational prescription, its impact and of drug misuse on health outcomes and economic co-relates. The effect of intervention in a selected hospital on prescription errors and drug misuse was assessed. The effect of drug misuse and multiple prescribed tablets on disintegration time, change in pH and viscosity of disintegration medium, aspects integrating the disciplines of Pharmaceutics, Pharmacy Practice and Clinical Pharmacy were also studied. Effect of self-directed/misunderstood doses of liquid medicines on disintegration time of co-prescribed tablets and pH and viscosity of disintegration medium was evaluated. Impact of medicine usage practices, i.e., use of milk on the above parameters was also studied. Response of 981 walk-in patients with 393 physicians and 618 MS personnel was received. The 57.21% physicians strongly agreed or agreed to have knowledge of cheaper generics of the same drug. Role of promotion by pharmaceutical companies (provision of samples and national and international trainings) was found influencing prescribing trends. The 57.5% physicians endorsed that they availed company sponsored training programs. Patients were concerned for medicine prices and 76.6% patients desired cheaper medicines to be prescribed. The 72.7% patients viewed that doctor should not have share/incentive on the prescribed medicines and 38.6% opined that multinational companies (MNCs) influenced prescribing because their medicine samples were present on physician’s table. The 77.7% MS staff informed that MNCs medicines, while 43.2% were of the view that local costly medicines are more prescribed. Brand replacement was indicated by considerable number (37.3%) of MS-staff and 72.8% of them opposed any share or incentives of physician in the discount given by the companies. Patients perception of medicine quality, discounts and promotions were the reasons of brand replacement. Price disparity was found in market for generics of the same drugs. The prescribers verified provision of knowledge updates for medicines through the representative of manufacturing firms. Such kind of detailing and perception has great potential of biasness and linked to economic prospective than mere knowledge up-gradation. Non uniform prices existed in the market. Firms supplied the same medicines to public sector hospital at different prices from the open market which were beyond 40% discount on the maximum retail price, allowed according to Federal Government of Pakistan under Price adjustment and discount Rules 2006. Hence huge profit margins might have the potentials for expenditures on un-ethical marketing. The majority of physicians, patients and MS-staff considered MNCs medicines as more effective. Physicians considered their prescribing as cost-effective but denied by majority of patients and MS personnel. The physicians and patients reported that medicines of local companies were not as effective as the MNCs medicines, which were contrary to what MS-staff thought. Majority of physicians disagreed that their prescribing was under the influence of medical stores in their vicinity, 40.5% patients response was in line with that of physicians whereas 32% MS personnel stated otherwise. Nearly half of the physicians strongly agreed or agreed that patients demanded medicines of the MNCs, but majority of patients and MS personnel denied it. For the impact of irrational prescriptions on health outcome, their economic co-relation and intervention on the irrational prescription in pediatric patients in a selected private sector hospital, 100 prescriptions were evaluated for errors and the legibility before, and after 2 and 15 months of intervention. Marked improvement in prescribing practices was observed 2 month after intervention with distribution of educational materials and discussions. The accuracy of dose was improved from 38% to 91%, treatment duration upgraded from 28% to 48% and for the diagnosis, the errors were reduced from 31% to 4%. Intervention impact persisted after 15 months but was declined. Overall possible cost impact of irrational prescription of cefixime oral liquid to children under age 10 years was found to be PKR 412545.64. It might be even higher since variability of the treatment plan, patient conditions, and unavailability of a system of reporting of adverse effects of the drug and/or certain non-quantifiable outcomes of the irrational prescription. The 83.9% of the 410 patients, selected through convenient sampling preferred bottle caps for taking oral liquid medicines. The 36.3% used to reconstitute dry powder suspension with very hot water. The reconstitution volume was taken by approximation by 69.5%. The 46.6% patients relied on the doctors and 37.6% on their relatives as the main source of instructions on medicine usage. Disinclination was observed to purchase full course of medicine. Knowledge of storage of medicines and measuring tools for oral liquids and disposal of leftover medicines shown striking peculiarities. Majority of patients mistook dessert spoonful/table spoonful as teaspoonful. Prescriptions having only tablet dosage forms were selected to evaluate effect of prescribed multiple tablets on in-vitro disintegration time of tablets and pH and viscosity of disintegration medium when given individually and in the prescribed combinations. To mimic the ways patients intake prescribed combinations of tablets either all at once or with some time difference, disintegration time of 41 prescribed combinations evaluated at following three conditions. In Condition I, prescribed tablets were taken individually in separate disintegration medium. In Condition II, all the tablet formulations prescribed on single prescription were placed all-at-once in medium and in Condition III, all the prescribed tablet formulations on one prescription was placed one-after-another with an interval of 10 min. The disintegration time was noted for tablets in all the above conditions, while the viscosity and pH of respective disintegration medium were evaluated at Conditions I and II only. The data of pH and viscosity of two tablet (designed as C2) and that of the three or more tablets (labelled as C≥ 3) were compared to the data of all combinations labeled as CT (data of C2+ C≥ 3). Degree of un-ionization to find the faction of drug available for absorption were computed for the prescribed combination with significant pH change in Condition I and II. The combination of two tablets shown significant changes in pH of respective disintegration media (p < 0.05). Being acidic or basic natured, the degree of deionization of drug in the combination of C2 in Condition I and II varied with changed pH of the disintegration media. The prescribed drug combinations affected the physicochemical parameters of in-vitro disintegration fluids, which ultimately might affect the bioavailability and therapeutic outcome. The 11 legible prescriptions having tablet formulations and at least one oral liquid were used to examine effect of misinterpretation of prescribed oral liquid dose as teaspoonful (5ml), dessertspoonful (10ml) or tablespoonful (15ml) or vice versa. The effect of different dose of oral liquids on disintegration time of co-administered tablets and physicochemical parameters of disintegration medium was noted. The disintegration time of each tablet on each prescription was separately measured in disintegration media containing 0.1 N HCl and co-prescribed oral liquid volume of 5 ml (Medium-I), 10ml (Medium-II) and 15 ml (Medium-III). The change in disintegration time of tablet and in pH and viscosity of three disintegration media was noted. The fraction of drug unionized was also computed where the pH of media changed dramatically. Quantity of oral liquid from 5ml to 15ml had changed the disintegration time of co-prescribed tablets and also pH and viscosity of respective disintegration media. The prescribed cefixime trihydrate showed marked change in fraction of drug un-ionization at changed pH due to its quantities as co-prescribed oral liquid with betamethasone tablet. For assessing the effects of prescribed multi tablet dosage forms and milk intake on disintegration time of tablets, pH and viscosity of disintegration medium at different test conditions, 10 legible prescriptions having tablet or tablets-syrup combinations were selected randomly from 849 prescriptions. Prescribed drug combinations per prescriptions were evaluated for disintegration time, their effect on pH and viscosity of disintegration media in two different conditions, i.e., 0.1N HCl and 50 % 0.1N HCl + 50 % milk. Disintegration time for some of prescribed tablets increased up to 5.21 times and decreased up to 1.22 times in milk-containing disintegration media when disintegration time of individual tablet was compared to that of multiple tablets or tablet-syrup formulations in one prescription. Viscosity of disintegration media was raised to peak of 3.69 times and declined to 2.58 times whereas pH was drastically increased in all prescribed combinations up to 15.89 times.