The effect of drug packaging on patients' compliance with treatment for Plasmodium vivax malaria in China Li Qingjun,l 4 Duan Jihui,2A Tang Laiyi,34 Zhang Xiangjun,4 Liang Jun,4 A. Hay,5 S. Shires,5 & V. Navaratnam6 A study conducted in 1994 showed that the use of blister packs containing antimalarial drugs significantly increased patients' compliance, compared with traditional means of dispensing drugs in a paper envelope. The present study assessed patients' compliance and compared the difference between 3-day chloroquine and 8-day primaquine courses of treatment for vivax malaria. The level of real compliance was determined bymarking the drugs with phenobarbital, and measuring its level in the blood following treatrnent. The results show that blisterpackaging significantly improvedpatients' compliance (P <0.001) over traditional means of dispensing antimalarial drugs; there was no difference in treatment compliance between 3-day and 8-day courses when the drugs were in blister packs. However, with ordinary packaging the treatment compliance rate for an 8-day course was significantly less than for a 3-day course (P < 0.05). Introduction from the container in a paper envelope or small pa- Hunan Province in south-central China comprises 14 per bag, and given to the patient without any identi- prefectures and 125 counties with a population of 64 fication of the drugs or written directions on their million. Since the start of the malaria control pro- use. The doctor's or health worker's oral instructions gramme in this province in the 1950s, there have to the patient on the number of tablets to be taken been three Plasmodiuim vivax malaria outbreaks and for how many days are brief and do not include with annual incidences of 1560 per 100000 in 1955, any advice or health education. Treatment is often 1690 per 100000 in 1962, and 1323 per 100000 in incomplete due to its discontinuation once the symp- 1971. Despite a comprehensive malaria control pro- toms have disappeared, or to disintegration or loss of gramme, the incidence since 1986 has risen and, for the tablets. Sometimes patients take an excessive counties in the south and south-west of the proNince, dose so as not to risk loss of the drug, and can expe- is five times higher than the provincial average. rience unpleasant side-effects. Chloroquine and primaquine are produced in Over 20 years ago, compliance was assured by China for the treatment of P. vivax malaria, and are delivering drugs on a daily basis to patients with generally dispensed by health workers from 1000- direct observation of therapy. While clearly effec- tablet bottles or tins. The current treatment regimen tive. this was unsustainable owing to the need for for adults is 4 chloroquine tablets (each containina large numbers of health workers. To improve com- 0.25mg chloroquine phosphate) on day 1, 3 tablets pliance and use of antimalarial drugs, a pilot inter- on days 2 and 3, and 3 tablets of 13.2mg primaquine vention study was undertaken to determine the daily from day 1 to 8. The curative dosage of each effects of new packaging of drugs and written is a instructions on compliance. drug dispensed by health worker or pharmacist The specific objectives of the study were as follows: IDirector. 2 Professor of Parasitology. - To compare the compliance of patients in 3Professor of Epidemiology. completing a full course of antimalarial treat- 4Health and Epidemic Prevention Station Hunan Province, ment; a control group received medication in pa- Changsha, Hunan, China. per envelopes and a second group were given the 5 Division of Clinical Sciences, School of Medicine, Old Medical improved packaging with simple, written instruc- School, University of Leeds, Leeds, England. tions on their use. e Director, Centre for Drug Research, Universiti Sains Malaysia, Penang, Malaysia. - To determine the possible reasons for non- Requests for reprints should be sent to Dr M. Gomes at the compliance in both groups and whether they address shown on p. 9. were related to the type of packaging and instruc- Reprnt No. 5847 tions on use. Builetin of the World Health Organization, 1998, 76 (Suppl. 1): 21-27 0 World Health Organlzation 1998 21 U QingJun et al. - To evaluate the impact of the new packaging and Hunan, the disease is introduced, causing epidemics of providing simple, written instructions with the of imported malaria. medication. Patients. The patients in the study were consenting - To determine the difference between reported adults (aged >15 years) with confirmed, slide- compliance (Phase-I study, based on only pa- positive vivax malaria; they were ambulatory, had tients' reports) and true compliance (Phase-Il no major clinical symptoms requiring hospitaliza- study, including use of a pharmacological marker tion, and had not received any malaria treatment inserted with each antimalarial tablet). during the previous 6 months. On selection at one of the clinic sites, a patient was randomly assigned either to the new drug packaging group or to the Materials and methods control group prior to receiving medication. Upon entry to the study, basic data were recorded on each Blister packs. The tablets of chloroquine and patient, including age, sex, occupation, suspected primaquine for the study were provided in two onse't of infection, clinical symptoms, laboratory packs, one for chloroquine (with daily doses sepa- test results, and date and time of treatment. When rated for three consecutive days) and the second for the drug regimen was completed in phase I and primaquine (with daily doses of 3 tablets for a total phase II, information was solicited on when the first of 8 days). The number 8, according to Chinese be- and last doses of the drug were taken, the total liefs, brings good luck and it was considered that a number of tablets taken, and on compliance and course of primaquine over 8 days would enhance non-compliance. compliance more than one for 14 days. Detailed oral instructions were given to the patients on the correct Phase J. As mentioned above, this phase was carried dosage and the need to complete the treatment. out in five counties of Hunan Province. Patients in The new blister pack was hermetically sealed, the control group were prescribed medication with separately for each day's supply of tablets, with the oral instructions on their use; the antimalarial tablets name of the drug on the back of the pack. The blister (chloroquine and primaquine) were put into a paper packs were inserted into boxes, with the drug name envelope and given to the patients. Patients in the on the front and dosage directions and precautions intervention group were prescribed medication with on the back; clear instructions were given on a leaflet identical oral instructions; the antimalarial tablets inside the box. Each pack measured 8 X 5.5cm and were given in two separate blister packs, marked contained 10 tablets of chloroquine for use over 3 with appropriate daily dosages and containing de- days, or 24 tablets of primaquine for 8 days. tailed written instructions. The advice given by the doctor to both the control and the intervention Study sites. For the phase I study, which was con- groups was the same regarding malaria and treat- ducted during the malaria season in 1994, the Health ment. However, each patient in the intervention and Epidemic Prevention Stations in five counties of group was asked to open the blister pack and read Hunan Province were selected as the study site. In the instructions for treatment found inside. When phase II, the Health and Epidemic Prevention they had finished reading the instructions, they were Stations in seven counties implemented the study in asked if they understood what they had just read. the malaria season from July till October 1996. The Patients in the control group were asked if they had choice of epidemic station in the counties was made understood the doctor's oral instructions. If the pa- so that a sufficient number of patients could be tient indicated a poor understanding, the instructions enrolled in the study period, which would ensure for treatment were repeated for both groups. that the study was carried out as designed. The quali- The sample size was determined using an expec- fications of the staff at these stations were high, and tation of 15% noncompliance in the control group each station had a good working relationship with and an expected 10% improvement in compliance the provincial authorities. (or 15% noncompliance) in the intervention group. During the study period, millions of people With a desired confidence level of 95%, a power of from Hunan Province migrated to Guangdong and 80%, and a ratio of 1:1 in the control and interven- Hainan Provinces where a high level of economic tion groups, the sample size was determined to be development was taking place. Most workers were 318 persons - 159 in the control group and 159 in engaged in mining and road and house constructions the intervention group. The choice of 15% noncom- in areas of high malaria endemicity. Malaria is com- pliance and an expected improvement in a compli- mon among the migrant. nonimmune populations ance of 10% was conservative as was also the sample and when these persons return to their homes in size. 22 WHO Bulletin OMS. Vol 76 (Suppl. 1) 1998 Effect of drug packaging on compliance with antimalarial treatment On day 9 (after the start of treatment), dav 1 followed by 3 capsules on each of days 2 and 3) each patient was either visited at home by a doctor in and 24 tablets total of primaquine over 8 days (3 the study team or patients returned to the Epidemic tablets daily for 8 days).