Regulation, consumption and expenditures of new cancer drugs in Ecuador and Latin America

The adoption and prescription of new cancer drugs, and the linked expenditures are rising very fast in Latin America (LA). This is compounded by the fact that an important number of new cancer drugs approved by regulatory authorities are failing to show real advantages in endpoints that really matter to cancer patients and health systems: to make patients live longer (overall survival) and better (quality of life), ideally both. In this thesis, we attempted to show the power of drug utilization research to inform evidence-based pharmaceutical policies, particularly those aimed at improving access to cost-effective new cancer drugs in LA countries. Findings from five research articles are presented along 5 main chapters. Chapter 1 describes the methodological challenges of comparing drug consumption between LA countries, based on a systematic review of studies in the region. Results highlighted the lack of studies analysing utilization data from both, the public and private healthcare sectors. Chapter 2 presents a 5-year (2010-2014) description of consumption and expenditures of cancer drugs from the 6 largest Ecuadorian public and private hospitals. Expenditures increased 22.6% annually, with new targeted cancer drugs acting as the main driver of the increase (76% of the total expenditures in 2014). In chapter 3, individual dispensing data from the same 6 hospitals are analysed (interrupted time series) to measure the impact of two policy interventions aimed at influencing the inclusion of new cancer drugs to the hospital therapeutic arsenal. In general, the combination of 2 levels of decision in the selection of new drugs (local and national) helped to control new prescriptions of costly targeted cancer drugs. Chapter 4 alerts about the weakness of scientific arguments behind regulatory decisions to approve new cancer drugs by regulators as European Medicines Agency (EMA) or US Food and Drug Administration (FDA), and warns about the dangers for developing countries when relying blindly on those decisions to approve new medicinal products. Chapter 5 assesses current national regulatory policies for the approval of new drugs in 34 LA and Caribbean countries, with a special focus on the concept of regulatory reliance. Results showed that 27 countries have explicit regulations that allow national regulators to directly accept or abbreviate the approval process when a new drug has been earlier approved by regulatory authorities located in other jurisdictions, mainly European, US and Canadian regulators. Finally, chapter 6 describes and discusses the impact of the approval of controversial new cancer drugs by EMA over marketing authorization decisions taken by some LA countries. We showed that 23 (of 28) new cancer drugs approved by LA regulators show no or very modest gain (less than three months) on overall survival. Likewise, LA countries approved most of the drugs that were EMA-approved based on clinical trials apprised to be at high risk of bias according to a scientific publication. The uncontrolled and quick adoption of expensive new cancer drugs could risk the health systems’ financial sustainability in countries like Ecuador. As show in our results, regulators play a fundamental role in ensuring the best possible therapeutic options for cancer patients. On one hand, LA regulators must assume a patient- and health system-centered approach, beyond the classic checklist checker of harmonized global rules, mostly built under an innovation-driven mentality. On the other hand, regulatory standards to approve new cancer drugs should be raised; and EMA, US FDA, Health Canada and other reputed regulators must assume this responsibility. Finally, this thesis highlights the importance of the proper collection of drug utilization data to monitor the implementation of health and pharmaceutical policies