Evaluating pharmaceutical policies using cross-national comparisons and time series analysis

The aim of this thesis was to evaluate the effects of different pharmaceutical policies on the use of medicines (e.g. antibiotics). These policies were evaluated using diverse data sources from the public and private sector in countries in Africa, Latin America, and Western Europe. In addition, the studies contained in this thesis explore and strengthen methods for policy evaluation, with a focus on time series analysis. The importance of cross-national comparisons is addressed together with the next steps to improve their reporting by adequate and detailed descriptions of data coverage and country characteristics such as marketing status of medicines and reimbursement policies to increase the validity and reliability of comparisons. Subsequently, the use of interrupted time series analysis (ITSA) and the application of this method in the evaluation of pharmaceutical policies is discussed. As an example of a pharmaceutical policy evaluation, the intended and unintended effects of the over-the-counter antibiotic sales restriction in Mexico and Brazil were assessed. Firstly, the size of the effect of the policy was measured using ITSA. Next, changes in the seasonal variation of penicillins were estimated as a proxy of appropriateness of penicillin use. Subsequently, unintended effects of the policy were assessed by measuring the changes in the use of therapeutic groups that can be perceived as substitutes of antibiotics to relieve cold symptoms (NSAIDs, analgesics, and cough and cold medicines). It was found that the usage level of antibiotics decreased in both countries by about 1 defined daily dose per 1,000 inhabitants per day (DDD/TID), with a decreasing trend in Mexico and an increasing trend in Brazil. The seasonal variation in penicillins decreased in Mexico by 0.4 DDD/TID after the restriction mainly due to changes in seasonal variation of amoxicillin and ampicillin, whereas changes in seasonal variation were not found in Brazil. Lastly, in the two countries, NSAIDs-analgesics usage changes were related with antibiotic usage changes, while only in Mexico cough and cold medicines usage changes had a relation with the antibiotics usage changes. These results showed a substitution effect on the use of other medicines, especially NSAIDs and analgesics, after the reinforcement of OTC antibiotics sales restrictions which might have unintended clinical consequences. It was concluded that although after the regulations the level of antibiotics decreased in both countries, interventions to improve the appropriateness of antibiotics are required. Furthermore, this type of policies should be comprehensive and take into account the potential substitution effects on the use of other medicines. Although ITSA has been one of the most used methodologies for the evaluation of pharmaceutical policies, further development and improvement of methodologies used in such studies is of great importance to guarantee evidence-based and effective policy-making. Applying other statistical tests in time series can improve the evaluation of policies by examining unintended effects and forecasting possible outcomes. The studies in this thesis show that the effects of interventions in the pharmaceutical sector need to be adequately quantified, and provide new approaches to do so which strengthens evidence-based policy making

Effects of over-the-counter sales restriction of antibiotics on substitution with medicines for symptoms relief of cold in Mexico and Brazil: time series analysis

We evaluated changes in the use of non-steroidal anti-inflammatory drugs (NSAIDs), non-opioid analgesics and cough and cold medicines and its relation with the use of antibiotics after the over-the-counter (OTC) antibiotic sales restrictions in Mexico and Brazil. IMS Health provided retail quarterly data from the private sectors in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. Data of each active substance of antibiotics, easily accessible medicines perceived as antibiotics substitutes (cough and cold medicines, analgesics and NSAIDs-the latter two being combined in the analyses), and medicines to control for external factors that can affect the medicines usage trend (antihypertensives) were converted from kilograms to defined daily doses per 1000 inhabitants days (DDD/TID). Interrupted time series were used to estimate changes in level of medicines use at the intervention point and slope after the regulation. The Gregory-Hansen cointegration test was used to explore the relation between the use of antibiotics and perceived substitutes. After the regulation in Mexico NSAIDs-analgesics usage level increased by 1.1 DDD/TID with a slope increase of 0.2 DDD/TID per quarter and the cough and cold medicines usage level increased by 0.4 DDD/TID. In Brazil NSAIDs-analgesics usage level increased by 1.9 DDD/TID, and cough and cold medicines did not change. In the two countries, NSAIDs-analgesics usage changes were related with antibiotic usage changes; in Mexico cough and cold medicines usage changes had a relation with the antibiotics usage changes. These results showed a substitution effect on the use of other medicines, especially NSAIDs and analgesics, after reinforcement of OTC antibiotics sales restrictions. These regulations aimed to improve the antibiotics use and as a consequence reduce antimicrobial resistance; however, this type of policies should be comprehensive and take into account the potential substitution effects on the use of other medicines

Evaluating pharmaceutical policies using cross-national comparisons and time series analysis

The aim of this thesis was to evaluate the effects of different pharmaceutical policies on the use of medicines (e.g. antibiotics). These policies were evaluated using diverse data sources from the public and private sector in countries in Africa, Latin America, and Western Europe. In addition, the studies contained in this thesis explore and strengthen methods for policy evaluation, with a focus on time series analysis. The importance of cross-national comparisons is addressed together with the next steps to improve their reporting by adequate and detailed descriptions of data coverage and country characteristics such as marketing status of medicines and reimbursement policies to increase the validity and reliability of comparisons. Subsequently, the use of interrupted time series analysis (ITSA) and the application of this method in the evaluation of pharmaceutical policies is discussed. As an example of a pharmaceutical policy evaluation, the intended and unintended effects of the over-the-counter antibiotic sales restriction in Mexico and Brazil were assessed. Firstly, the size of the effect of the policy was measured using ITSA. Next, changes in the seasonal variation of penicillins were estimated as a proxy of appropriateness of penicillin use. Subsequently, unintended effects of the policy were assessed by measuring the changes in the use of therapeutic groups that can be perceived as substitutes of antibiotics to relieve cold symptoms (NSAIDs, analgesics, and cough and cold medicines). It was found that the usage level of antibiotics decreased in both countries by about 1 defined daily dose per 1,000 inhabitants per day (DDD/TID), with a decreasing trend in Mexico and an increasing trend in Brazil. The seasonal variation in penicillins decreased in Mexico by 0.4 DDD/TID after the restriction mainly due to changes in seasonal variation of amoxicillin and ampicillin, whereas changes in seasonal variation were not found in Brazil. Lastly, in the two countries, NSAIDs-analgesics usage changes were related with antibiotic usage changes, while only in Mexico cough and cold medicines usage changes had a relation with the antibiotics usage changes. These results showed a substitution effect on the use of other medicines, especially NSAIDs and analgesics, after the reinforcement of OTC antibiotics sales restrictions which might have unintended clinical consequences. It was concluded that although after the regulations the level of antibiotics decreased in both countries, interventions to improve the appropriateness of antibiotics are required. Furthermore, this type of policies should be comprehensive and take into account the potential substitution effects on the use of other medicines. Although ITSA has been one of the most used methodologies for the evaluation of pharmaceutical policies, further development and improvement of methodologies used in such studies is of great importance to guarantee evidence-based and effective policy-making. Applying other statistical tests in time series can improve the evaluation of policies by examining unintended effects and forecasting possible outcomes. The studies in this thesis show that the effects of interventions in the pharmaceutical sector need to be adequately quantified, and provide new approaches to do so which strengthens evidence-based policy making

Analysing policy interventions to prohibit over-the-counter antibiotic sales in four Latin American countries

OBJECTIVES: To describe and evaluate policies implemented in Chile, Colombia, Venezuela and Mexico (1995-2009) to prohibit antibiotic OTC sales and explore limitations in available data. METHODS: We searched and analysed legislation, grey literature and peer-reviewed publications on regulatory interventions and implementation strategies to enforce prohibition of OTC antibiotic sales. We also assessed the impact using private sector retail sales data of antibiotics studying changes in level and consumption trends before and after the policy change using segmented time series analysis. Finally, we assessed the completeness and data quality through an established checklist to test the suitability of the data for analysis of the interventions. RESULTS: Whereas Chile implemented a comprehensive package of interventions to accompany regulation changes, Colombia's reform was limited to the capital district and Venezuela's limited to only some antibiotics and without awareness campaigns. In Mexico, no enforcement was enacted. The data showed a differential effect of the intervention among the countries studied with a significant change in level of consumption in Chile (-5.56 DID) and in Colombia (-1.00DID). In Venezuela and Mexico, no significant change in level and slope was found. Changes in population coverage were identified as principal limitations of using sales data for evaluating the reform impact. CONCLUSION: Retail sales data can be useful when assessing policy impact but should be supplemented by other data sources such as public sector sales and prescription data. Implementing regulatory enforcement has shown some impact, but a sustainable, concerted approach will be needed to address OTC sales in the future