Data Rich, Information Poor: Can We Use Electronic Health Records to Create a Learning Healthcare System for Pharmaceuticals?

Judicious use of real-world data (RWD) is expected to make all steps in the development and use of pharmaceuticals more effective and efficient, including research and development, regulatory decision making, health technology assessment, pricing, and reimbursement decisions and treatment. A "learning healthcare system" based on electronic health records and other routinely collected data will be required to harness the full potential of RWD to complement evidence based on randomized controlled trials. We describe and illustrate with examples the growing demand for a learning healthcare system; we contrast the exigencies of an efficient pharmaceutical ecosystem in the future with current deficiencies highlighted in recently published Organisation for Economic Co-operation and Development (OECD) reports; and we reflect on the steps necessary to enable the transition from healthcare data to actionable information. A coordinated effort from all stakeholders and international cooperation will be required to increase the speed of implementation of the learning healthcare system, to everybody's benefit.

The risks of risk aversion in drug regulation.

Drugs are approved by regulatory agencies on the basis of their assessment of whether the available evidence indicates that the benefits of the drug outweigh its risks. In recent years, regulatory agencies have been criticized both for being overly tolerant of risks or being excessively risk-averse, which reflects the challenge in determining an appropriate balance between benefit and risk with the limited data that is typically available before drug approval. The negative consequences of regulatory tolerance in allowing drugs onto the market that turn out to be unsafe are obvious, but the potential for adverse effects on public health owing to the absence of new drugs because of regulatory risk-aversion is less apparent. Here, we discuss the consequences of regulatory risk-aversion for public health and suggest what might be done to best align acceptance of risk and uncertainty by regulators with the interests of public health.

Bridging the efficacy-effectiveness gap: a regulator's perspective on addressing variability of drug response.

Drug regulatory agencies should ensure that the benefits of drugs outweigh their risks, but licensed medicines sometimes do not perform as expected in everyday clinical practice. Failure may relate to lower than anticipated efficacy or a higher than anticipated incidence or severity of adverse effects. Here we show that the problem of benefit-risk is to a considerable degree a problem of variability in drug response. We describe biological and behavioural sources of variability and how these contribute to the long-known efficacy-effectiveness gap. In this context, efficacy describes how a drug performs under conditions of clinical trials, whereas effectiveness describes how it performs under conditions of everyday clinical practice. We argue that a broad range of pre- and post-licensing technologies will need to be harnessed to bridge the efficacy-effectiveness gap. Successful approaches will not be limited to the current notion of pharmacogenomics-based personalized medicines, but will also entail the wider use of electronic health-care tools to improve drug prescribing and patient adherence.

European regulation on orphan medicinal products: 10 years of experience and future perspectives.

In 2000, regulation on orphan medicinal products was adopted in the European Union with the aim of benefiting patients who suffer from serious, rare conditions for which there is currently no satisfactory treatment. Since then, more than 850 orphan drug designations have been granted by the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products (COMP), and more than 60 orphan drugs have received marketing authorization in Europe. Here, stimulated by the tenth anniversary of the COMP, we reflect on the outcomes and experience gained in the past decade, and contemplate issues for the future, such as catalysing drug development for the large number of rare diseases that still lack effective treatments.

Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers.

Drug regulatory agencies have traditionally assessed the quality, safety and efficacy of drugs, and the current paradigm dictates that a new drug should be licensed when the benefits outweigh the risks. By contrast, third-party payers base their reimbursement decisions predominantly on the health benefits of the drug relative to existing treatment options (termed relative efficacy; RE). Over the past decade, the role of payers has become more prominent, and time-to-market no longer means time-to-licensing but time-to-reimbursement. Companies now have to satisfy the sometimes divergent needs of both regulators and payers, and to address RE during the pre-marketing stages. This article describes the current political background to the RE debate and presents the scientific and methodological challenges as they relate to RE assessment. In addition, we explain the impact of RE on drug development, and speculate on future developments and actions that are likely to be required from key players.

No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products--a pilot study.

BACKGROUND: Regulators and payers have to strike a balance between the needs of the patient and the optimal allocation of resources. Drugs indicated for rare diseases (orphan medicines) are a special group in this context because of their often high per unit costs. Our objective in this pilot study was to determine, for drugs used in an outpatient setting, how utilisation of centrally authorised drugs varies between countries across a selection of EU member states. METHODS: We randomly selected five orphan medicines and nine other drugs that were centrally authorised in the European Union between January 2000 and November 2006. We compared utilisation of these drugs in six European Union member states: Austria, Denmark, Finland, Portugal, The Netherlands, and Sweden. Utilisation data were expressed as Defined Daily Doses per 1000 persons per year. Variability in use across countries was determined by calculating the relative standard deviation for the utilisation rates of individual drugs across countries. RESULTS: No association between orphan medicine status and variability in use across countries was found (P = 0.52). Drugs with an orphan medicine status were more expensive and had a higher innovation score than drugs without an orphan medicine status. CONCLUSIONS: The results show that the variability in use of orphan medicines in the different health care systems of the European Union appears to be comparable to the other newly authorised drugs that were included in the analysis. This means that, although strong heterogeneity in access may exist, this heterogeneity is not specific for drugs with an orphan status.

Delayed nausea and vomiting continue to reduce patients' quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. We compared the impact of acute (during the first 24 hours postchemotherapy) and delayed (days 2 through 5 postchemotherapy) CINV on patients' quality of life (QoL) after highly or moderately emetogenic chemotherapy (HEC and MEC, respectively). PATIENTS AND METHODS: This prospective, multicenter, multinational study was conducted in 14 medical practices on cancer patients undergoing either HEC or MEC treatment. Patients recorded episodes of nausea and vomiting in a diary. Patients completed the Functional Living Index-Emesis (FLIE) questionnaire at baseline and on day 6. RESULTS: A total of 298 patients were assessable (67 HEC patients, 231 MEC patients). Emesis was reported by 36.4% of patients (13.2% acute, 32.5% delayed) and nausea by 59.7% (36.2% acute, 54.3% delayed). HEC patients reported significantly lower mean FLIE total score than MEC patients (95.5 v 107.8 respectively; P = .0049). Among all patients, the nausea score was significantly lower than the vomiting score (50.0 and 55.3, respectively; P = .0097). Of the 173 patients who experienced neither vomiting nor nausea during the first 24 hours postchemotherapy, 22.9% reported an impact of CINV on daily life caused by delayed CINV. CONCLUSION: CINV continues to adversely affect patients' QoL despite antiemetic therapy even after treatment with only moderately emetogenic chemotherapy regimens, and even in the subgroup of patients who do not experience nausea and vomiting during the first 24 hours. On the basis of the FLIE results in this study, nausea had a stronger negative impact on patients' daily lives than vomiting.