Report on the current status of the use of real-world data (RWD) and real-world evidence (RWE) in drug development and regulation.

Radically expanding use of real-world data (RWD) and real-world evidence (RWE) holds the potential to substantially impact drug development, pharmaceutical regulation, and payment within health care systems. Central to this is the reconfiguration of data gathering and transformation of data to information, which can be used as evidence for decision making. We discuss applications of this paradigm in the light of recent developments in both the United States and Europe on RWD and RWE.

Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications.

BACKGROUND: Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy's clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. MATERIALS AND METHODS: We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). RESULTS: Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups). CONCLUSION: Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs. IMPLICATIONS FOR PRACTICE: Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in preauthorization trials (type of endpoint [hard/surrogate], magnitude of endpoint outcome, and its statistical significance) and whether they are associated with a positive regulatory outcome. Clinicians can use these properties, which are described in the publicly available European public assessment reports, to help guide their understanding of the clinical effect of new oncologic therapies.

Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients.

OBJECTIVE: To ascertain the current burden of adverse drug reactions (ADRs) through a prospective analysis of all admissions to hospital. DESIGN: Prospective observational study. SETTING: Two large general hospitals in Merseyside, England. PARTICIPANTS: 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission. MAIN OUTCOME MEASURES: Prevalence of admissions due to an ADR, length of stay, avoidability, and outcome. RESULTS: There were 1225 admissions related to an ADR, giving a prevalence of 6.5%, with the ADR directly leading to the admission in 80% of cases. The median bed stay was eight days, accounting for 4% of the hospital bed capacity. The projected annual cost of such admissions to the NHS is 466m pounds sterling (706m Euros, 847m dollars). The overall fatality was 0.15%. Most reactions were either definitely or possibly avoidable. Drugs most commonly implicated in causing these admissions included low dose aspirin, diuretics, warfarin, and non-steroidal anti-inflammatory drugs other than aspirin, the most common reaction being gastrointestinal bleeding. CONCLUSION: The burden of ADRs on the NHS is high, accounting for considerable morbidity, mortality, and extra costs. Although many of the implicated drugs have proved benefit, measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit:harm ratio of the drugs.

Reporting of adverse drug reactions by nurses.

Schemes for spontaneous reporting of adverse drug reactions are important to post-marketing safety surveillance worldwide. In the UK, doctors, dentists, coroners, and pharmacists are allowed to report through the yellow card scheme, but nurses were not until October, 2002. We used a similar programme to assess the role of community and hospital nurses in reporting of adverse drug reactions. The proportion and quality of reports received from nurses was similar to that of those received from doctors: we received reports from one in seven nurses eligible to report, compared with one in eight doctors; 137 of 177 nurse reports and 676 of 984 doctor reports were judged to be appropriate according to regulatory authority criteria (95% CI for difference between proportions 1.4-15.0, z=2.3, p=0.02). Our findings suggest that nurses, who form the largest proportion of health-care staff in the UK, can play a valuable part in improvement of pharmacovigilance.