February, 2011 - SUPPORT Summary of a systematic review | print this article |
Millions of people contract malaria each year. The WHO currently promotes artemisinin-based combination therapy (ACT) for treating uncomplicated malaria, but this may be more difficult for patients to adhere to correctly than other treatments.
Packaging a course of treatment in units of a single dose may be a more effective way of ensuring that patients take the correct dosage, and thus of increasing treatment success
Millions of people contract malaria each year, mainly in areas such as sub-Saharan Africa, South-East Asia and South America.
The WHO currently promotes artemisinin-based combination therapy (ACT). Unless the drugs are coformulated, people are often required to follow a regimen that includes more than one antimalarial drug at a time. Such regimens may be more difficult to follow correctly than single therapies. If treatment responses relate to the dose and schedule of a therapy, non-adherence may reduce treatment benefits.
Packaging a course of treatment in units of a single dose may help to ensure better that the correct dosage is taken and thus to increase the success of treatment.
The packaging systems adopted by different countries and pharmaceutical companies vary widely. Some types of packaging, such as the the WHO-recommended blister packaging for artemisinin-based regimens, require certain levels and types of technology. Variations are also found in the products developed within this packaging type.
Review Objectives:To summarise the effects of unit-dose packaged treatment on treatment failure and treatment adherence in people with uncomplicated malaria | ||
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What the review authors searched for |
What the review authors found |
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Interventions | Randomised controlled trials (RCTs) and quasi-RCTs evaluating programmes that include unit-dose packaging of antimalarial drugs |
1 RCT, 1 cluster RCT, and 3 quasi-RCTs evaluating labelled and boxed blister packs of chloroquine and primaquine tablets and capsules (2 studies) and simple, labelled and sectioned polythene bags of chloroquine tablets (3 studies) |
Participants |
People diagnosed with uncomplicated malaria infection |
People with uncomplicated malaria confirmed clinically (2), microscopically (2), or using both methods (1) |
Settings | Any setting |
Outpatient health centres in China (2), Ghana (2) and Papua New Guinea (1) |
Outcomes | Treatment failure, treatment adherence and adverse events |
None of the trials reported on treatment failure but all reported on some of the following: parasitaemia, clinical symptoms, wellness of the child, cure according to medical notes and the perception of participants, and the recrudescence of infection. All 5 trials reported on treatment adherence. Adverse events were measured in 2 studies |
Date of most recent search: February 2009 | ||
Limitations: This is a good quality systematic review with only minor limitations |
Orton LC, Barnish G. Unit-dose packaged drugs for treating malaria. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD004614. See in Cochrane Library
This review found five studies conducted in LMIC settings that evaluated and compared the use of labelled and boxed blister packs and simple, labelled and sectioned polythene bags, with the use of paper envelopes, bottled syrup or unsectioned bags. All studies measured adherence and some measure of treatment success (none measured treatment success as suggested by the WHO), but only two reported adverse events.
Two studies in adolescents and adults evaluated the use of boxed blister packs that had the drug name on the blister pack and inside the box. These packs were used for a 3-day course of the drug chloroquine and an 8-day course of primaquine, taken each day together from individual blister units.
The use of blister packs compared with the use of paper envelopes |
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Patient or population: Uncomplicated malaria Settings: Any setting Intervention: Blister-packed tablets and capsules Comparison: Tablets and capsules in paper envelopes |
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Outcomes | Comparative risks* |
Relative effect (95% CI) |
No of Participants (studies) |
Quality of the evidence (GRADE) |
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Without blister-packs | With blister-packs |
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Treatment failure |
In one of the two studies, all participants (intervention and control) were aparasitaemic and asymptomatic at the end of the treatment period. In the other study, one of the 57 participants in the comparison group had recrudesced at day 88 (there were no such occurrences in the intervention group) |
Not estimable |
596 |
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Treatment non-adherence |
18 per 100 |
3 per 100 |
RR 0.14 |
596
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CI: Confidence interval RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page) |
One study in children aged 0 to 5 years, evaluated the use of hermetically sealed, sectioned polythene bags containing daily doses of chloroquine tablets (labelled ‘1’, ‘2’, or ‘3’ to indicate the day of dosage) and compared this with the provision of the same drug in bottled syrup form.
The use of sectioned polythene bags compared with bottled syrup |
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Patient or population: Children with uncomplicated malaria |
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Outcomes | Comparative risks* |
Relative effect (95% CI) |
No of Participants (studies) |
Quality of the evidence (GRADE) |
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Without polythene bags |
With polythene bags |
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Treatment failure |
Most participants in both the groups were considered by their caregivers to have fully recovered by the end of the treatment period |
Not estimable |
299 |
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Treatment non-adherence |
58 per 100
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10 per 100 |
RR 0.16 |
299
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Adverse events |
Of the 155 participants receiving tablets, 28 vomited some of the medication and six vomited all the tablets | Not estimable |
299 |
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CI: Confidence interval RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page) |
One study of adults and children (7+ years) compared the use of hermetically sealed, sectioned polythene bags containing daily doses of chloroquine tablets (labelled ‘1’, ‘2’ or ‘3’ to indicate the day of dosage), with the same dosage provided in paper envelopes.
The use of sectioned polythene bags compared with the use of paper envelopes |
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Patient or population:Uncomplicated malaria |
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Outcomes | Comparative risks* |
Relative effect (95% CI) |
No of Participants (studies) |
Quality of the evidence (GRADE) |
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Without polythene bags |
With polythene bags |
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Treatment failure
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The wellness of most participants improved at the end of treatment (intervention: 152 improved, 13 unchanged, 2 worsened; control: 143 improved, 4 unchanged, 5 worsened) |
Not estimable |
319 |
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Treatment non-adherence |
40 per 100 |
19 per 100 (13 to 27) |
RR 0.46 |
319 |
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Adverse events | Similar incidence of itching, dizziness and other adverse events | Not estimable |
319
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CI: Confidence interval RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page) |
One study in adults evaluated a 3-day regimen of drugs were administered in sealed, clear and sectioned polythene bags stapled to a card base with the daily dosage of tablets in each colour-coded section, and the name of the drugs and instructions written below each section.
The use of sectioned polythene bags compared with polythene bags (unsectioned) |
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Patient or population: Uncomplicated malaria Settings: Any setting Intervention: Tablets in sectioned polythene bags Comparison:Polythene bags (unsectioned) |
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Outcomes | Comparative risks* |
Relative effect (95% CI) |
No of Participants (studies) |
Quality of the evidence (GRADE) |
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Without sectioned bags |
With sectioned bags | ||||
Treatment failure
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No significant difference in the cure rate at day four (intervention 77/91 compared with control 96/112) |
Not estimable |
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Treatment non-adherence
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5 per 100 |
2 fewer per 100 |
RR 0.77 |
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Adverse events | The study did not measure adverse events | Not estimable | |||
CI: Confidence interval RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page) |
Findings | Interpretation* |
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APPLICABILITY | |
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EQUITY | |
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ECONOMIC CONSIDERATIONS | |
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MONITORING & EVALUATION | |
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*Judgements made by the authors of this summary, not necessarily those of the review authors, based on the findings of the review and consultation with researchers and policymakers in low- and middle-income countries. For additional details about how these judgements were made see: http://supportsummaries.org/support-summaries/how-support-summaries-are-prepared/ |
Related literature
Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD000011
Horne R, Weinman J, Barber N, Elliot R, Morgan M. Concordance, adherence and compliance in medicine taking: a scoping exercise. London: NCCSDO; 2005.
This summary was prepared by
Gabriel Rada, Unit for Health Policy and Systems Research, Faculty of Medicine, Pontificia Universidad Católica de Chile, Chile
Conflict of interest
None declared. For details, Conflicts of interest
Acknowledgements
This summary has been peer reviewed by: Lois Orton, UK; Paul Garner, UK
This summary should be cited as
Rada G. What are the effects of using drugs packaged in unit doses to treat malaria? A SUPPORT Summary of a systematic review. February 2011.