The Impact of a Neutral Formulated and Designed Package Insert on Nocebo-effect. (NEUPANO)

Neutral Formulated and Designed Package Insert or Only Verbal Information Compared to Package Insert According EU-directive: a Pilot Randomised Controlled Trial to Analyse the Influence on the Nocebo Effect and Non-adherence

Background The nocebo effect describes the association between the expectation of negative effects, (e.g. side effects) and the actual occurrence of negative effects. Studies have shown that the nocebo effect can be influenced by (risk) communication. Till today there is no study that compares different types of information on adverse events regarding the strength of the nocebo effect.

Aim The aim of this pilot randomized controlled trial is to analyse the influence of different communication types on the frequency and intensity of adverse events and adherence. To increase the relevance and applicability of the results the study intervention builds up on package inserts because these are the most widespread form of information on side effects.

Methods Patients It is planned to include 60 patients in the study.

Intervention

• Modified package insert: simplified and focused on neutral risk perception. The representations and formulations are based on the findings from research on evidence-based patient information and risk communication. The package insert contains the same information as the statutory package insert to ensure that it complies with the legal requirements.
• Verbal information about side effects: The patient is informed verbally about side effects and does not receive any package insert.

Control Package insert according to EU (European Union) Directive 2001/83 / EC (European Commission) (usual package insert).

Outcomes

• Number of patient reported adverse events (primary outcome).
• Adherence (correct initiation of therapy, correct intake amount, premature discontinuation of therapy).
• Resource use (e.g. provider contacts).

Type of study Monocentric, outcome assessor, three-arm, randomised controlled pilot trial.

Study Overview

• Status: Unknown
• Conditions: Orthopedic Surgery
• Intervention / Treatment: Other: Package Insert

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • North-Rhine-Westfalia
    • Cologne, North-Rhine-Westfalia, Germany, 51109
      • Clinic for orthopedics, trauma surgery and sports traumatology, hospital Cologne Merheim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• elective orthopaedic surgery
• planned intake of ibuprofen 600 mg to treat postoperative pain
• postoperative pain medication other than Ibuprofen 600 (Opioids, Opiate, Paracetamol) no longer than 1-2 days postoperative (until discharge)
• at least 18 years
• able to speak German
• no cognitive deficits
• written informed consent

Exclusion Criteria:

• serious comorbidity
• pain medication prior to surgery
• other medication with similar side effects
• polytrauma
• planned inpatient rehabilitation > one week after hospital discharge

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modified Package Insert; Simplified and focused on neutral risk perception. The representations and formulations are based on the findings from research on evidence-based patient information and risk communication. The package insert contains the same information as the statutory package insert to ensure that it complies with the legal requirements.	Other: Package Insert; Modified package insert of Ibuprofen given postprocedural as pain medication; Other Names: Patient Education
No Intervention: Verbal Information; The patient is informed verbally about side effects and does not receive any package insert.
Active Comparator: Control; Package insert according to EU Directive 2001/83 / EC (usual package insert)	Other: Package Insert; Modified package insert of Ibuprofen given postprocedural as pain medication; Other Names: Patient Education

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patient reported adverse events	Any reported adverse events	6-9 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence	Correct initiation of therapy, correct intake amount, premature discontinuation of therapy	6-9 days after surgery
Resource use	e.g. provider contacts	6-9 days after surgery

Collaborators and Investigators

• Sponsor: University of Witten/Herdecke
• Collaborators: German Research Foundation
• Investigators: Principal Investigator: Tim Mathes, Dr., Witten/Herdecke University

Publications and helpful links

General Publications

• Prediger B, Meyer E, Buchter R, Mathes T. Nocebo effects of a simplified package leaflet compared to unstandardised oral information and a standard package leaflet: a pilot randomised controlled trial. Trials. 2019 Jul 26;20(1):458. doi: 10.1186/s13063-019-3565-3.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): September 30, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: February 2, 2018
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 5, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Randomized controlled trial; nocebo; package insert
• Other Study ID Numbers: V01-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study protocol and clinical study report will be shared as supplement with the journal publication
• IPD Sharing Time Frame: 2019
• IPD Sharing Access Criteria: Will be published as electronic supplement with the journal publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No