Table 1 Studies analysing the impact of law enforcement activities to prohibit OTC sales of antibiotics in lower- or middle-income countries
Study and setting | Outcome (data source) | Method | Intervention | Results | Methodological issues |
|---|---|---|---|---|---|
Mattos et al. [16] 2017 Brazil | Changes in antibiotic sales (IMS Health data) AMR trend (E. coli resistance patterns) | Observational | • Retention of prescriptions • Inspections | Decrease in total sales of antibiotic not paralleled by decrease in AMR. Increasing trend in E. coli resistance seen in all antibiotic classes, except nitrofurans and folate pathway inhibitors. | Resistance data was obtained from one teaching hospital in Brazil and sales data from drugstores in the same metropolitan were analysed. Statistical analyses were used to verify linear resistance rates, but not to assess correlation between resistance patterns and differences in sales data. Other research indicated that low antibiotic sales do not necessarily correlate with low antibiotic resistance rates in LMICs [29]. |
Moura et al. [17] 2015 Brazil | Changes in total antibiotic use and shifts in therapeutic classes (IMS Health data) | ITS | • Retention of prescriptions • Inspections | • Direct effect on sales: − 1.87 DID • Penicillin, sulfonamide, macrolide sales decreased • The increasing trend in antibiotic sales tempered after the intervention (total increase in sales 2008–2012: 6.48 to 7.52 DID) | The study by Moura et al. included public antibiotic sales data to assess differences in direct policy impactbetween the private and public sector. Monthly antibiotic sales between January 2008 and December 2012 were analysed. |
Santa-Ana-Tellez et al. [18] 2013 Brazil Mexico | Changes in total antibiotic use and shifts in therapeutic classes (IMS Health data) | ITS | • Retention of prescriptions (Brazil and Mexico) • Inspections (Brazil and Mexico) • Media campaign (Mexico) | Brazil • Direct effect on sales: −1.35 DID • Penicillin, sulfonamide, macrolide sales decreased • No change in increasing sales trend (total increase in sales Q1 2007-Q2 2012: 5.7 to 8.5 DID, + 49.3%) Mexico • Direct effect on sales: − 1.17 DID • Penicillin and sulfonamide sales decreased • No change in decreasing sales trend (total decrease in sales Q1 2007-Q2 2012: 10.5 to 7.5 DID, − 29.2%) | Sales data of antihypertensives were used as reference group to account for changes in medicine use independently of the OTC restrictions directed at antibiotics. Quarterly antibiotic sales between January 2007 and June 2012 were analysed. |
Santa-Ana-Tellez et al. [19] 2015 Brazil Mexico | Changes in seasonal variation in penicillin sales (IMS Health data) | ITS | • Retention of prescriptions (Brazil and Mexico) • Inspections (Brazil and Mexico) • Media campaign (Mexico) | No significant differences in Brazil. Variation between penicillin sales in summer and winter decreased by 0.4 DID (− 36%) in Mexico. | High seasonal variation in penicillin use is suggested to be associated with more inappropriate use of antibiotics [30]. The authors suggest that appropriate use of antibiotics might mean that less antibiotics are sold without a prescription. |
Lopes-Júnior et al. [20] 2015 Brazil | Changes in antibiotic sales in 3000 pharmacies | Before-after measurement | • Retention of prescriptions • Inspections | Tetracyclines (− 30.47%), sulfonamides (− 28.54%), macrolides (− 24.99%), and penicillins (− 20.46%)sales decreased. Only the sales of amoxicillin clavulanic acid seemed to increase (+ 9.14; not significant). | The study reported the annual sales data before and after the intervention. The results could not be seen in perspective of antibiotic sales patterns in other years around the intervention. |
Wirtz et al. [21] 2013 Chile Colombia Venezuela | Changes in total antibiotic use and shifts in therapeutic classes (IMS Health data) | ITS | • Retention of prescriptions (Chile, Venezuela) • Inspections (Chile, Venezuela) • Media campaign (Chile, Colombia) • Involvement of pharmacists in designing enforcement (Chile) | Chile • Direct effect on sales: − 5.56 DID • Penicillin and sulfonamide sales decreased • No significant change sales trend (total decrease in sales Q1 1997-Q2 2002: 12.3 to 8.5 DID) Colombia • Direct effect on sales: on sales − 1.00 DID • Penicillin and sulfonamide sales decreased • No change in sales trend (total decrease in sales Q2 2002-Q4 2007: 9.16 to 6.76 DID) Venezuela • No direct reduction of antibiotic sales • Penicillin sales increased • No change in increasing sales trend (total increase in sales Q1 2003-Q4 2008: 9.99 DID to 15.38 DID) | Multiple countries were included in this study and analysed by means of the same method. Therefore, the policy impact in different could be compared to some extent. Since the researcher used an ITS analysis, they were able to directly relate the results to the policy intervention(s). |
Bavestrello et al. [15] 2011 Chile | Changes in total antibiotic use (IMS Health data) | Observational | • Retention of prescriptions • Inspections • Media campaign • Involvement of pharmacists in designing enforcement | From 2000 to 2002 the impact of regulation persisted, but from 2003 to 2008 the total level of antibiotic use in Chile raised from 7.57 to 9.91 DID. | The authors did not take changes in antibiotic sales trend before the intervention into consideration. Therefore, it is almost impossible to make a strong conclusion based on this data. |
Marković-Peković et al. [22] 2017 Bosnia and Herzegovina | Changes in OTC supply of antibiotics in 131 (2010) and 383 (2015) pharmacies | Mystery client method Before-after measurement | • Retention of prescriptions • Inspections • Media campaign | 58% of investigated pharmacies sold antibiotics OTC to mystery clients presenting with self-diagnosed urinary tract infection in 2010 versus 18.5% in 2015. | The researchers assessed the policy impact on actual practice of pharmacists in supplying antibiotics OTC. The mystery clients presented at the pharmacies with the same symptoms during all visits to assure comparability. |
Bojanić et al. [23] 2018 Bosnia and Herzegovina | Changes in total antibiotic use and shifts in therapeutic classes (National PHI) | Before-after measurement | • Retention of prescriptions • Inspections • Media campaign | The total sales of antibiotics did not significantly differ between 2010 and 2015 (17.6 and 16.8 DID respectively). Sales of amoxicillin-clavulanic acid and azithromycin increased | Since multiple law enforcement initiatives were instigated over the complete period of analysis, the researchers were unable to conduct an ITS analysis. Therefore, it is difficult to relate the results and assess the actual impact of the multifaceted intervention. |
Abilova et al. [24] 2017 Azerbaijan | Changes in total antibiotic use and shifts in therapeutic classes (wholesaler import data) | Observational | • Retention of prescriptions • Inspections • Media campaign • Education of pharmacists | Total antibiotic use decreased by −9.08 DID between 2011 and 2015. Sales of tetracyclines, macrolides, and fluoroquinolones rose, while sales of beta-lactam antibiotics decreased. | Since multiple law enforcement initiatives were instigated over the complete period of analysis, the researchers were unable to conduct an ITS analysis. Therefore, it is difficult to relate the results and assess the actual impact of the multifaceted intervention. |
Ivanovska et al. [25] 2018 North Macedonia | Changes in reported practice and knowledge regarding antibiotic use in 1203 clients | Survey Before-after measurement | • Retention of prescriptions • Inspections • Media campaign | Children self-medication rates decreased in 2015 and increased in 2016. No other changes were seen in client knowledge, attitude or behaviour. | Due to the short period between the survey rounds, the impact of the specific national media campaign on cliental knowledge could be assessed. Since the survey was conducted three times, some assumptions could be drawn about long-term impact. However, this methodology outcome does not capture the effect of interventions other than media campaigns. |
Chuc et al. [26] 2002 | Changes in OTC supply of antibiotics in 68 pharmacies | Mystery client method Quasi-experimental | • Inspections • Education of pharmacists | Fewer pharmacies dispensed cefalexin without a prescription after the interventions (from 95 to 56%) in the intervention pharmacies compared to control pharmacies (from 94 to 89%). | Due to the quasi-experimental design, the researchers could correct for other factors influencing the availability of antibiotics without a prescription, meaning that the results could be attributed to the policy intervention. However, due to the small sample size and since all pharmacies were located in one geographical area, the generalisability of the study can be questioned. |
Chalker et al. [27] 2005 Vietnam Thailand | Changes in OTC supply of antibiotics in 68 (Vietnam) and 78 (Thailand) pharmacies | Mystery client method Quasi-experimental | • Inspections • Education of pharmacists | 69% instead of 90% of pharmacies sold low dose antibiotics OTC after the intervention in Vietnam. No reduction in pharmacies selling antibiotics OTC in Thailand. | The results can be linked to the research interventions, due to the quasi-experimental study design that was used. However, due to the small sample size and since all pharmacies were located in one geographical area, the generalisability of the study can be questioned. |
Arparsrithongsagul et al. [28] 2015 Thailand | Changes in OTC supply of antibiotics and Changes in reported practice and knowledge regarding antibiotic use in 116 groceries | Mystery client method and survey Quasi-experimental | • Inspections • Education of pharmacists | Fewer groceries sold antibiotics after the intervention (22.9% versus 79.2%), while there was little change in the control group. | The reduction in availability of antibiotics can be attributed to the intervention, due to the quasi-experimental study design that was used. All included grocery stores were located in one province. Therefore, the representativeness for Thailand as a whole can be questioned. |
Chalker et al. [31] 2001 Vietnam | Changes in reported practice and knowledge regarding antibiotic use in 44 pharmacies | Survey Quasi-experimental | • Inspections • Education of pharmacists | Fewer pharmacists claimed they would sell cefalexin without a prescription after the intervention (20% versus 57%). | The results can be linked to the research intervention, due to the quasi-experimental study design that was used. Using reported practice by pharmacists makes the study vulnerable for social desirability bias. |