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Given the extensive development of new molecules over the last 10 years, regulatory authorities (RAs) have been intensively working on evaluating how to identify and manage "innovative" drugs. The purpose of this article is to analyze whether RAs have procedures capable of ensuring access to innovative drug therapies and to understand what criteria RAs around the world (Europe, USA, Canada, Australia, and Japan) use to identify innovative drugs, comparing the different strategies and tools used to prioritize the assessment of the most promising drugs. All the RAs under review consistently use two elements to speed up drug access: (1) the handling (shortening) of approval times and the (2) management of the (limited) evidence available. No international RA utilizes any state-of-the-art method to evaluate the innovativeness of medicinal products. Harmonizing a definition and the criteria used to define pharmaceutical innovation would allow faster access to patients.

Background: In 2010, the European Medicines Agency (EMA) initiated a pilot project on parallel scientific advice with Health Technology Assessment bodies (HTABs) that allows manufacturers to receive simultaneous feedback from both the European Union (EU) regulators and HTABs on their development plans for medicines., Aims: The present retrospective qualitative analysis aimed to explore how the parallel scientific advice system is working and levels of commonality between the EU regulators and HTABs, and among HTABs, when applicants obtain parallel scientific advice from both a regulatory and an HTA perspective., Methods: We analysed the minutes of discussion meetings held at the EMA between 2010, when parallel advice was launched, and 1 May 2015, when the cutoff date for data extraction was set. The analysis was based on predefined criteria and conducted at two different levels of comparison: the answers of the HTABs vs. those of the regulators, and between the answers of the participating HTA agencies., Results: The analysis was based on 31 procedures of parallel scientific advice. The level of full agreements was highest for questions on patient population (77%), while disagreements reached a peak for questions on the study comparator (30%). With regard to comparisons among HTABs, there was a high level of agreement for all domains., Conclusions: There is evident commonality, in terms of evidence requirements between the EU regulators and participating HTABs, as well as among HTABs, on most aspects of clinical development. Indeed, regardless of the question content, the analysis showed that a high level of overall agreement was reached through the process of parallel scientific advice., (© 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: The process leading to a regulatory outcome is guided by factors both related and unrelated to the data package, defined in this analysis as 'formal and informal factors', respectively. The aim of this qualitative study was to analyse which formal and informal factors drive the decision-making process of the European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulators with regard to anticancer drugs, using in-depth semi-structured interviews with regulators of the two agencies., Methods: In line with the theory and practice of qualitative research, no set sample size was defined a priori. Respondent enrolment continued until saturation and redundancy were reached. Data were collected through means of in-depth semi-structured interviews conducted either in a face-to-face setting or via Skype(®) with each regulator. The interviews were audio-recorded and verbatim transcribed. The analysis was manually carried out on the transcribed text. Data were independently coded and categorized by two researchers. Interpretation of the findings emerged through a process of triangulation between the two., Results: Seven EMA and six FDA regulators, who had extensive experience with making decisions about anticancer medicines, were interviewed between April and June 2012. There is an open dialogue between the FDA and EMA, with the two moving closer and exchanging information, not opinions. Differences in decision-making between the agencies may be due to a different evaluation of end points. Different interaction modalities with industry and patients represent an additional source of divergence with a potential impact on decision-making. The key message of our respondents was that the agencies manage uncertainty in a different way: unlike the EMA, the FDA has a prevailing attitude to take risks in order to guarantee quicker access to new treatments., Conclusions: Although formal factors are the main drivers for regulatory decisions, the influence of informal factors plays an important role in the drug evaluation process.

Purpose: The aims of this study were to compare the approaches of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in the evaluation and approval of new anticancer indications and to identify possible clinical implications associated with these differences., Methods: Information on the European Union therapeutic indications for the cohort of anticancer drugs was extracted from the European Public Assessment Reports and from the FDA review reports., Results: Overall, 42 anticancer drugs were approved by EMA between 1995 and 2008, corresponding to a total of 100 indications. In 47 of 100 indications, a difference was found. For 19 of these 47 indications, the difference was that one agency approved an indication, whereas the other agency did not. For the remaining 28 indications, the same indication was approved by both of the agencies and differences were evaluated through an algorithm; in 10 cases, discrepancies in therapeutic indications between EMA and FDA were considered clinically relevant. We found an overall trend that the agency that was second to give a positive approval was usually more restrictive in terms of wording of the indication compared with the agency that provided approval first. Regarding the use and robustness of available clinical data for evaluation, no clear associations could be found., Conclusion: Clinically relevant differences in the outcome of the EMA and FDA approval process of oncology products were found. Neither of the agencies seems to have a prevailing restrictive behavior over the other. Further efforts on harmonizing decision making between regulatory systems are needed.

The regulatory route leading to the definition of therapeutic indications of new compounds as well as extensions of indication (EoI) of already approved ones is a challenging process. If new anticancer drugs reach the market with a lack of complete evidence, this usually leads regulators to request additional data, post approval commitments or restrictions in therapeutic indications. This study aims at quantifying the time needed for anticancer drugs approved by the EMEA to get an extension, the rates and characteristics of extensions approved, and at exploring the regulatory process leading to the definition of new indications. A total of 103 therapeutic oncological indications, related to a cohort of 43 anticancer drugs, were retrieved between 1995 and 2008. The median time occurring between different indications for the same compound (defined as Time to New Extension, TtNE) significantly decrease from about 81 months in 1996 to 6 months in 2006. Twenty-four out of 43 approved anticancer medicines (about 56%) have only a single therapeutic indication, 12 of which were approved before 2005. When considering two different cohorts of drugs in relation to the time of approval (1995-2004 versus 2005-2008), although not statistically significant, the older cohort tended to have a decreased probability of having EoI when compared to the new cohort (OR=0.27; 95% confidence interval (CI): 0.07-1.04). With regard to the type of EoI (n=60), our findings showed that in 48% of cases the initially approved indication was extended to treat a different tumour, in 37% of cases the extension consisted in a switch of line within the same therapeutic indication. The other two types of indication broadening refer to a different tumour stage (8%) and to the inclusion of a new patient population (7%). The analysis of indication restrictions showed that in 20 cases out of 50 (40%) therapeutic indications were restricted by the Committee for Medicinal Products for Human Use (CHMP) during the assessment, with 60% of the restrictions occurring in 2006-2007. This study adds three main pieces of information: (i) the majority of anticancer drugs still have a single indication regardless of the year of approval; (ii) the time needed to obtain an extension of indication has decreased significantly over the last decade and (iii) a highest rate of regulatory restrictions is matched to shorter clinical developments., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Objective: Current European regulations only require drugs to be safe and effective, although there is heavy demand for comparative efficacy data to demonstrate the added value of new drugs. The objective of the analysis reported here was to assess the added value of new anticancer drugs for haematological malignancies that have been approved by the European Medicines Agency (EMEA) based on the clinical data provided at the time of submission., Methods: Information on the evidence supporting the approval was extracted from the European Public Assessment Reports (EPARs). Documents were surveyed for new applications and for subsequent extensions between January 1995, when the EMEA was set up, and May 2006. The added value of newly approved drugs was assessed by an algorithm that evaluates the strength of evidence based on methodological appropriateness (randomised comparison) and the importance of clinical advantage (in terms of the magnitude of benefit, hardness of outcome measures, adequacy of comparator)., Results: Eleven anticancer drugs were analysed. Of 17 indications, nine (53%) were approved on the basis of single-arm trials (SATs), and eight (47%) were approved on the basis of randomised controlled (clinical) trials (RCTs). The most frequently used endpoint was response rate (12 of 17 indications, 70%). On the basis of our criteria, only four of the 11 drugs show a consistent added value., Conclusion: We were unable to establish an added value for about two thirds of the drugs evaluated in this study, primarily due to methodological aspects related to study design and endpoint robustness.