Switch Timely to Oral Medication (STORM)

Methods

o Study design

A prospective, mono-centric, interrupted time series interventional study will be carried out starting in August 2015. Patients will be recruited hospital wide, except for patients admitted at the ICU or pediatric wards. The study protocol will be send for approval to the Clinical Trial Centre and Ethics Committee. Based on the NIH, Code of Federal Regulations Chapter 45-46, an exemption on informed consent is requested at Ethics Committee in order to prevent bias by informing physicians and/or patients; as there's only a suggestion to alter therapy to the treating physician and no clinical intervention is planned and data are processed anonymously and retrospectively, patient safety and patient rights are guaranteed. The study protocol will be registered in the public registry ClinicalTrials.gov.

o Inclusion and exclusion criteria and general assessment process

All prescriptions for levofloxacin (J01MA12), moxifloxacin (J01MA14), clarithromycin (J01FA09), fluconazole (J02AC01), clindamycin (J01FF01), acetaminophen (N02BE01), rifampicin (J04AB02), ornidazole (J01XD03) and metronidazole (J01XD01) in the hospitals CPOE from 01-08-2015 until 30-11-2015 for all hospitalized patients will be included.

The following prescription-related information will be requested from the HIS: unique hospitalisation number, patient name (needed for contact with prescriber), date of prescription, identification of prescriber, ward number, discipline, medication, route of administration, dose.

The sample size of the dataset is not limited in order to provide the maximum power to the study. The number of patients is estimated at 4000 per month.

o Building the dataset

A daily stored query, as presented in Figure 1, will the CPOE for therapies with at least one of the nine bio-equivalent drugs and fulfillment of the other criteria, such as presence of an order of a meal or prescription for other oral solid drugs and absence of a prescription of parenteral nutrition or an order for enteral feeding . The working procedure and the stored query are validated by 3 senior staff hospital pharmacists with expertise in the domain and approved by the Pharmacy&Therapeutics Committee (MFC).

The time scheme of the study is presented in Figure 2, and consists of the following blocks:

• Baseline monitoring periods: During month 1 and 3, the query will be run without intervention. The results of the query are captured in a database in order to have baseline data before starting both the intervention periods.
• Intervention period 1: During month 2, a team of trained staff pharmacists, who are assisted under close supervision by master students of the Faculty of Pharmaceutical Sciences, contact the prescribers by telephone, guided by the suggestions and information of the operating procedure. The number of contacted prescribers and their responses (acceptance or not) are recorded in the database. To do so, a standard operating procedure for telephone contact with the prescribers will be available for the co-investigators.
• Intervention period 2: During month 4, a computer algorithm will leave an electronic follow-up note suggesting the potential IV to oral switch, along with the argument to do so, in the medical record.

Due to dispensing of the medication and his interdisciplinary task in optimizing therapy the hospital pharmacist is related to the patient and has access to the necessary data; the pharmaceutical record is part of the patients' medical record. Nevertheless the access to the medical records is, as always, subject to approval by the medical council. Use of data is subject to a confidentiality agreement, an official confidentiality agreement between hospital and each co-investigator will be signed.

The solely intend of the access to the medical record is to gather data on the potential IV/PO switch and possible contra-indications. There will be no intervention in any way in the therapy nor the patient - physicians relationship. Reporting will be anonymous, never on an individual patient or physician.

Impact of initiation time of the study At the University Hospitals Leuven, August is the moment where most new prescribers enter the hospital. To avoid bias from this prescriber switch, the switch period is excluded from the timing. Therefore, in concrete, baseline monitoring period 1 will be started up in September 2015.

Avoidance of potential bias To avoid learning bias from the prescribers, a wash-out period is included before each intervention period. A poster on possible IV-PO switch will distributed in the hospital and published on the intranet webpage at the start of each period of the study.

o Analysis of database

General analysis of the database will be done in Microsoft Access 2013. More in detail, descriptive statistics will be carried out using appropriate parametric or non- parametric tests (Student t-test, Mann-Whitney U-test or Chi square, based on distribution of data) to describe the demographics of the included patients.

Statistical analysis will be carried out in SPSS or SAS by the investigator in collaboration with L-Biostat (KU Leuven).

o Pharmacoeconomic analysis

Based on the dataset (time-to-switch and price of medication) the potential cost-saving from a healthcare payer perspective will be calculated using the list price at 01-11-2015 of the involved medication. Cost-avoidance due to lesser infections or lesser length of stay cannot be calculated with this dataset.