Pharmacoepidemiology for oncology clinical practice: Foundations, state of the art and perspectives

Since the early 2000s, the arrival of the so-called targeted therapies and immunotherapies have prolonged survival rates in many cancers. In parallel, post-marketing surveillance of anticancer drugs through pharmacoepidemiology has gradually developed. This paper provides (i) a detailed argumentation of the foundations for pharmacoepidemiology of anticancer drugs, (ii) an overview of pharmacoepidemiological studies currently available in this field, and (iii) some perspectives to improve pharmacoepidemiology for oncology practice. First of all, according to the existing literature, the development of pharmacoepidemiological studies for the clinical evaluation of anticancer drugs appears particularly justified based on common limitations of clinical trials in oncology regarding essential methodological principles such as adequate control groups, randomisation or double blinding. Many descriptive field cohort studies have investigated together treatment patterns, effectiveness, and safety to compare results from clinical trials with those of everyday practice. The utilisation of anticancer drugs has also been extensively described through cross-sectional or cohort studies by often using medico-administrative or medical databases. Such studies are useful to quantify and characterise use over time in the population, including clinically unvalidated use, and to evaluate adherence and persistence to increasingly available oral anticancer drugs. Despite their importance to increase knowledge, comparative effectiveness or safety studies remain uncommon. In a context of rapidly emerging therapies and personalised treatments, this may be due to methodological challenges especially related to the choice of a comparator or the consideration of confounding by indication. In the future, efforts must be pursued to provide real-time access to high-quality, large-scale clinical, biological and treatment data, and to improve record-linkage between hospital and outpatient databases. More research is also needed to better evaluate all medications, not only anticancer, as part of an overall cancer care pathway and to bring the evaluation of anticancer drugs closer to patients and society (social pharmacology)

The Multidimensional Nature of Research Ethics: Letters Issued by a French Research Ethics Committee Included Similar Proportions of Ethical and Scientific Queries

Debate is ongoing concerning the activities and functioning of Research Ethics Committees (REC), especially a possible science-or-ethics dichotomy in research ethics review. We retrospectively analyzed 145 letters issued by a French REC over 18 months. All queries were classified in three levels: qualification (definition of the problem), category (aggregation of broader topics) and finally fields (ethical, scientific, or administrative). Overall, 971 queries were identified, of which 407 (42%), 379 (39%), and 135 (14%) were deemed ethical, scientific, and administrative queries, respectively. The most frequent concern was about participants' information. The main influencing factor was the profession of the reporting readers-scientific queries were more frequently raised by a methodologist, whereas ethical queries were more frequently raised by an ethicist. These results indicate that research ethics review is a multidimensional task that should be considered a collaborative effort

J Geriatr Oncol

Treatment of metastatic colorectal cancer (mCRC) has been modified since the launching of targeted therapies. Colorectal cancer (CRC) is common in elderly patients; their representation in randomized controlled trials (RCTs) is thus crucial. This study aimed to evaluate and quantify the inclusion of elderly/frail patients in RCTs of targeted therapies in mCRC. A systematic review using Medline, Scopus, Cochrane Database and ISI Web of Science was performed to identify all phase II/III RCTs of bevacizumab, cetuximab, panitumumab, regorafenib and aflibercept in mCRC until January 2015. Two reviewers independently performed studies selection, and data extraction. The protocol was registered in Prospero (CRD42015016163). Among 1,369, identified publications, 54 RCTs were selected. Nine RCTs (17%) excluded elderly patients; median age of the included population was <65years old in 50 RCTs (93%). Twenty RCTs (37%) excluded frail patients, and many RCTs excluded patients with uncontrolled hypertension or heart failure, patients treated with specific drugs (mainly anticoagulants), and patients with inadequate creatinine clearance. Elderly/frail patients are underrepresented in RCTs studying targeted therapies in mCRC, and those elderly patients included in RCTs do not reflect well the general elderly population with mCRC because of the exclusion criteria. RCTs results concerning targeted therapies can be inferred only to relatively healthy elderly subjects

Ambulatory drug changes in the elderly after hospital discharge: A cohort study

AIM: To describe the ambulatory changes in drug prescriptions 3 months after hospital discharge among elderly patients aged 75 and over, and to identify the reasons for these changes. METHODS: A prospective cohort study was conducted on subjects, discharged between 09/2016 and 01/2017 from the Bordeaux University Hospital. Prescription forms were collected from patients' pharmacists. The main outcome was the occurrence of at least one significant change (SC) defined as an initiation, a discontinuation, a switch or change in drug daily dosage as regards the drugs prescribed upon hospital discharge and those prescribed 3 months after. Whenever drug SC occurred, general practitioners were requested to elicit reasons for such changes. RESULTS: Among the 126 patients included in our study, 73 underwent a 3-month follow-up period, without death or being re-hospitalised. 87.7% of them had at least one SC 3 months after discharge, with an average of 3.1±2.5 SC per patient. Main changes involved: discontinuation or dose decrease of anxiolytics, hypnotics, antalgics, betablockers and calcium channel blockers; start or dose increase of diuretics, ACE inhibitors and angiotensin receptor blockers. In patients with a 3-month follow-up period, 27.4% underwent at least one ADR-induced SC. CONCLUSION: Most elderly patients experience drug prescription changes after discharge. Some, according to drug iatrogenic, could be avoided through better cooperation between hospital and ambulatory prescribers

Adverse drug reactions induced by cotrimoxazole: still a lot of preventable harm

Owing to a broad spectrum and low cost antimicrobial, cotrimoxazole is largely prescribed. However, its use is associated with various adverse drug reactions (ADRs) that warrant to ensure rational prescribing. This study aimed to describe spontaneous reports of cotrimoxazole ADRs and to evaluate the quality of prescription in patients who had ADRs. Suspected cotrimoxazole-induced ADRs cases reported to the Bordeaux regional pharmacovigilance centre (France) during a five-year period were described. Seriousness was assessed according to international criteria. Quality of prescription was assessed by compliance with the Summary of Product Characteristics (SPC) and relevance of cotrimoxazole indication. Then, an ADR was considered as preventable if the cotrimoxazole indication was not relevant, or potentially preventable if indication was relevant but the prescription was not compliant with the SPC. A total of 96 cases were analyzed: median age was 60.5 years (range: 4-94); 59.4% of patients were male. ADRs were mostly cutaneous disorders (n = 46) and hematological disorders (n = 25). A total of 60 serious ADRs occurred in 55 patients. Prescribers complied with all SPC recommandations in 21.9% of cases. Indication of cotrimoxazole was relevant or highly relevant in 41 cases. In 58% of cases, the occurrence of a cotrimoxazole-induced ADR would have been preventable or potentially preventable. In a context of increasing interest for this antibiotic to treat infections due to resistant bacteria, physicians should be more aware of the potential consequences of inappropriate prescribing cotrimoxazole and reserve its use when there is no alternative and under suitable monitoring