Evaluating the centralized purchasing policy for the treatment of hepatitis C: The Colombian CASE

Abstract The high cost of drugs for hepatitis C limits access and adherence to treatment. In 2017, the Colombian health care system decided to design a strategy. It consisted of centralized purchasing, regulations, clinical practice guidelines, and direct observation of the treatment and follow‐up of patients. The main objective of this study was to assess the centralized purchasing strategy in Colombia. The study design was a policy implementation assessment. We analyzed the change in prices, the clinical outcomes, and the opinions of stakeholders using data from the Ministry of Health. Additional information about effectiveness came from the Colombian Fund for High‐Cost Diseases and semi‐structured interviews of the stakeholders. The follow‐up was from October, 2017 to October, 2018. The total number of patients reported in the cohort period was 1069. The number that finished 12 weeks of treatment, completed the follow‐up for the case closure, and were considered cured through the end of October, 2018 was 563 (53%). The remainder, 506 patients (47%), are currently in treatment. A total of 543 of these treated patients (96%) were cured. After implementing this strategy, the drug prices decreased by more than 90% overall. Before implementation, the total direct cost was $100 102 171.75 dollars. Afterward, the cost was $8 378 747 dollars.


| INTRODUC TI ON
The World Health Organization (WHO) estimates that there were 130 to 150 million cases of hepatitis C (hep C) infection worldwide in 2015, which caused approximately 1 300 000 deaths that year.
This death rate is increasing over time. 1 Hep C is a liver disease caused by a virus of the same name. The disease could be acute or chronic, with symptoms lasting from a few weeks to one's entire life. 2 The major complications due to persistent viremia are liver fibrosis, cirrhosis, hepatocellular carcinoma, and death. 2 These complications represent an essential burden of disability adjusted life years.
Innovation in the pharmaceutical industry is a critical factor in health care systems around the world. Some of the new drugs improve the health status and quality of life in communities. Hep C is not an exception. In the last few years, improvements have been made in the treatment of hep C, including Direct Acting Antiviral (DAA) drugs, which are better tolerated and have a higher effectiveness rate of 95% virological response than interferon-based treatments. 3 With access to medicine, the health burden caused by hep C could be lessened. Drugs to cure the disease are available. There are significant health benefits for patients, such as high rates of curation and high levels of drug safety. Likewise, for the health care system, the benefits include cost savings and a reduction in the population risk by decreasing transmission. Some of the spillover effects are: a positive impact on out of pocket expenditures and an improvement in the effective access to treatment. However, the price of these drugs is extremely high, which limits access. 4 However, 97% of the Colombian population currently has the same coverage and guaranteed access to new technologies. The health care expenditure per person in Colombia is one-fifth that of developed countries. Nevertheless, the inclusion of new technologies is crucial to maintaining the legitimacy of the system, but this situation represents a sustainability problem. 5 Centralized purchasing has been identified as a possible solution.
Colombia was the first country in the Americas to acquire this type of high-cost treatment through the help of the Strategic Fund of the Pan American Health Organization (SF PAHO). 6,7

| Centralized purchasing in Colombia
The National Viral Hepatitis Control Plan developed by the  Given the relevance of the centralized drug purchasing strategy for hepatitis as a public policy in Colombia, the objective of this study was to evaluate its impact on the health care system, taking into account clinical, economic, and administrative impacts.

| MATERIAL S AND ME THODS
The study design is a policy implementation assessment. The intervention was the centralized purchasing of treatments for hep C made • Designing policies that contribute to regulating drug prices is a priority for health care systems.
• The centralized negotiation and purchasing for hep C treatment will procure savings for the health care system.
• The centralized negotiation and purchasing for hep C treatment will lead to positive health results.
by the Ministry of Health in Colombia. The endpoints were clinical effectiveness, savings for the health care system, and stakeholders' perceptions. Information from the Ministry of Health was used, including the prices of the reimbursement for treatments, prices of the drugs purchased by means of this strategy, the quantity needed, and the number of cases with a confirmed diagnosis reported to the National Epidemiological Surveillance System. Additional information came from the CAC, which contained facets of clinical and pharmacological follow-up. Also, they provided data on the effectiveness of the therapy, which is defined by the undetectable viral load 12 weeks after finishing the therapy, including all of the patients who received treatment as a result of the centralized purchase. Finally, other information came from semi-structured interviews of the stakeholders.

| Statistical analysis
We developed descriptive statistics of demographic information, summary measures, and measures of central tendency. We calculated and compared the differences in price and the savings before and after centralized purchasing. The quantity of drugs purchased was analyzed, with the assumption that a patient requires 84 doses for the complete treatment. The purchase prices used for the analysis were the prices reported in the purchase orders that the PAHO issued to the MSPS.

| Qualitative analysis
In order to know and assess the opinions of the stakeholders, a qualitative approximation by way of semi-structured interviews was used, which incorporated the following elements: (1) knowledge of the centralized purchasing strategy, (2) planning, (3) implementation, Stakeholders were selected by identifying who the key players in implementing this policy were. an infection from HIV, and the most prevalent genotype among the reported patients was 1B.

| Economic results
The centralized purchase of drugs for hep C included Daclatasvir, Sofosbuvir and Ledipasvir/Sofosbuvir. Table 3 shows the previous prices, the prices with the centralized purchase, the quantities purchased, and the savings obtained. clinical experts (hepatologists and infectologists). They considered this to be the prescription pattern.

| Stakeholder opinions
Supporting information, Table S2 shows the stakeholders who participated in the semi-structured interviews (see the online appendix). Table S3 shows the results from the semi-structured interviews of the key players in the health care system. Figure 1 shows the principal categories and most frequent comments made by stakeholders.

In the Supporting information,
The responses were subdivided into strengths before and after implementation of the strategy. The interviewees felt that the strengths prior to implementation were related to the comprehensive strategy design. This is understood to mean that they include GPCs, pathways, regulations, and information systems. These are used for follow-up, an adequate planning process that incorporates a review of information sources, prioritization of health conditions based on a review of the research, the participation of all of the players involved, and their commitment to the strategy.
Regarding strengths after the implementation, the interviewees felt that the strategy led to direct benefits for the health care system and the patients. This was due to the creation of cost-effective actions, increased access to timely therapy, quality of care, and the fact that more than 98% of the patients adhered to the strategy.
Of equal importance was the feeling that it was a strategy that involved an efficient use of resources and financial sustainability for the health care system. Finally, there was a direct benefit to the health care teams, evidenced by the positive impact on the health of the patients.
Several opportunities were identified regarding the centralized purchasing strategy. First, the calculation of quantities needed did not take into account the subsidized health care system. Also, there were some problems in primary care levels for screening and early detection. Moreover the prevalence of hep C was overestimated.
The last issue was the lack of recognition of the strategy and its results by the academic world.
In terms of suggested actions for the future, the interviewees recommended continuing the centralized drug purchasing and negotiation strategy in a comprehensive way. In addition, they endorsed looking for new ways to identify and prioritize health conditions and technologies, strengthening training at primary care levels for screening, and striving for early detection for patients. Finally, they suggested including the subsidized health care system in these policies and strategies.

| D ISCUSS I ON
High drug prices are a burden on health care systems. This has been addressed by different price regulation policies including external reference pricing, annual price adjustments according to market competition, regulation of price increases, centralized purchasing and negotiation, regulation and evaluation of patent time frames, and regulation of price ceilings, among others. 14,15 The Colombian health care system has implemented a price regulation policy for drugs that includes three types of regulation: regulated freedom, direct control, and freedom under surveillance. This control have reduced price inflation by almost 43%. However, the real pharmaceutical cost rose, mainly due to an increase in the quantities sold. As a result, the price fixing mechanism should be used together with market regulation. 16 These findings are consistent with those reported by other authors, who consider that drug price regulation policies should be comprehensive and include more than one strategy, plus an analysis of micro-and macroeconomic factors. 14,[17][18][19] In 2017, the Colombian health care system decided to include centralized drug purchasing for hep C as a strategy to reduce prices and increase access to treatment.
This is the first article to assess this policy for the treatment of The most important elements of the plan that played an essential role in its success, aside from the centralized purchase, were the stakeholders' participation and engagement with the strategy. The strategy was comprehensive and considered the perspectives of the government, insurance companies, patients, physicians, medical teams, pharmacists, and the pharmaceutical industry. This guaranteed transparency and successful implementation.
That said, there is still room for improvement. For example, the subsidized health care system was not included, so they were unable to access the same reduced prices for hep C treatment. However, it is worth mentioning that this did not limit the insurance companies from buying and delivering drugs to those who needed them within the subsidized system. One stakeholder comment was related to the calculation of the affected population, suggesting an overestimation of cases. This is a challenge for the information system and the strategies for centralized purchasing and negotiation, since one of the objectives was price reduction by aggregated demand. In addition, for the strategy to continue, it is critical to assure transparency between the key players, the health care system, and the pharmaceutical companies. 20 One year after implementing centralized drug purchasing for This research has some limitations, one of which is not including the analysis of drug prices for the subsidized health care system because it was not included in the centralized purchasing. Also, there is a lack of clinical results from this population, given that the information system designed to record them did not include the report from the subsidized system.
Health care systems around the world have implemented different strategies to reduce drug prices and improve access. The main objective is to look for alternative options for the future. One choice is the Netflix Model, in which a subscription fee is paid to a pharmaceutical company. This would reduce the possibility of strategic behavior from these companies, ensure that patients have access to drugs, and decrease inequalities.

| CON CLUS ION
The centralized drug purchasing strategy for hep C developed and implemented by the Colombian Health Ministry was a success. The creation of policies designed to reduce drug prices and improve access and quality for patients to achieve improved health results should be a priority of the health care system. It should allow these implemented strategies to continue, along with a comprehensive plan for innovations in new strategies.

ACK N OWLED G EM ENTS
This project was carried out based upon grant 859-2017 awarded by Colciencias.

D I SCLOS U R E S
None of the authors have a conflict of interest.

AUTH O R S ' CO NTR I B UTI O N S
Angela V. Pérez and Johnny D. Contreras authors are Designed research, conducted research, analyzed data, wrote paper, responsibility for the final content. Antonio J. Trujillo, Aurelio E. Mejia and Joshua M. Sharfstein authors are Analyzed data, wrote paper, responsibility for the final content.

E TH I C A L A PPROVA L /S TATE M E NT E A N OT R EQ U I R E D
This research does not require an ethical approval because this study analyzed secondary data, the information is public, and our analysis is aggregated.
The interviewers approved the publication of the results of the interview because the data and analysis were aggregated.

S TATE M E NT A B O UT PR I O R P OS TI N G S A N D P R E S E N TAT I O N S
The abstract of this research was accepted for a poster presentation at the 35th International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE 2019).