Research protocol
Research protocol
January 2019, Version 1
Objective
The purpose of the Hidradenitis suppurativa registry (HSR) is to evaluate the long-term course, safety clinical outcomes and health related quality of life of patients with Hidradenitis suppurativa (HS). Patient will be enrolled in the HSR with a confirmed HS diagnosis only and treated in the participating centers. Patients will remain in in the HSR for 3 years, regardless of subsequent therapy.
Background
Hidradenitis suppurativa (HS) is a multifactorial, chronic, recurrent, debilitating, inflammatory skin disease, which can lead to severe scarring and disability and is associated with reduced quality of life, depression, working disability, pain, social stigmatization and cardiovascular risk factors. It is an under-recognized and under-studied skin disease. Currently there are only few studies for the management of HS (systemic treatment and surgery) and most often the rationale for the use of most systemic treatments and surgery is based on low level of evidence. Many critical clinical and epidemiological questions remain unanswered. There is hardly any evidence on the benefit/risk ratio of treatments, both short- and long-term. Risk factors and natural course of the disease are largely under-studied. There is great variation in treatment offered on a European level. Recent data indicate that the disease is strongly associated with working disability. All the above-mentioned evidence indicates that it is crucial to obtain valid answers in time to many clinical and epidemiological questions regarding HS. The development of a registry of HS patients is an important and scientifically valid method to study and answer many clinical and epidemiological hypotheses. The registry will provide real life data, including post marketing surveillance. It will facilitate development of predictive models, will lead to multiple benefits both on clinical and research level. The registry will enhance a European collaboration and benefit the management of HS patients.
Objectives
The objective of the current project is the development the registry for HS patients. The register aims to recruit and enroll all patients with HS that are diagnosed and treated in the participating centers. The register will undertake the responsibility to deliver consensus reports, expert recommendations and annual updates from the register. A core data set of important variables, both physician and patient rated, will be collected in specific time points.
Tasks, milestones and timelines
Planning and development of the web-based registry was established within the last two years.
Registry start is planned for April 2019 (first patient in).
Methods
The population or sample to be studied
Centers
Dermatological practices and hospital outpatient departments in Switzerland (possible collaborations with Germany /Austria planned in the future) with adequate expertise in treatment of HS are the population of providers of care. Centers are willing to enter the documentation electronically.
Treatments
Observation starts with the initiation of a systemic treatment applied for the first time. As described previously, the treatment is performed according to the current drug regulation and according to the European and national guideline on HS treatment. The registry is based on observational data only, therefore there are no limitations to treatment.
Patients
The population of patients is constituted of all patients with a diagnosis of HS in Switzerland. The actual patients of the participating study centers define the accessible population. The population is sparsely confined by following in- and exclusion criteria.
Inclusion criteria
- Patients with diagnosis of HS confirmed by a dermatologist,
- Age >18,
- Being administered a specific systemic drug for the first time
- Sufficient language skills (German, French, Italian and English) for the informed consent to participate
- Informed consent to participate
Exclusion criteria
- Lack of informed consent
Centers
Recruitment of patients will take place in dermatologic practices and clinics.
Recruitment and Course of study
Inclusion into study
If a patient would like to participate, after being informed and handed a patient information sheet about the study, an informed consent will be signed.
Each patient will be registered online (formoffice.com) by their physician and receives a unique identifier.
Patients may choose to state their E-Mail address to receive the patient CRF beforehand per E-mail, or decline to do so and fill them out during consultations.
Each participating center will keep a key list that matches the names and birthdays of the patients with their identifying code in a locked drawer or cupboard.
Patients will visit 6 times the specific HS-center (month 0,3,6,9,12,18). The physician will fill out an eCRF each time. At Month 0, an “inclusion eCRF” and at the other points in time a follow-up eCRF will be filled out.
Data will be obtained from the patient at visit 2,3,4,5,6 by paper based CRF or filled in directly by dermatologist in the electronic CRF (eCRF) and dermatologist directly by standardized electronic questionnaires (eCRF) or paper based CRF.
Data entry will be performed using appropriate database interface entry forms. The relational database will include all outcomes data as well as the patient basic data.
Recordings will be made according to international standards for epidemiological studies (“Good Epidemiological Practice”), the usual outcome parameters for psoriasis and in compliance with the AWMF-Guideline for Recording Quality of Life in Dermatology.
The following outcomes will be recorded at the start and over the course of the study:
- Clinical parameters
- Severity of disease
- Patient reported outcomes:
- Health-related quality of life (disease-specific and generic)
- Patient-defined benefit
- Sleep quality
- Quality of care
- Therapy characteristics
- Adverse Events (AE, SAE)
Follow-up
Each follow-up appointment will be scheduled in the doctor’s office according to the documentation scheme.
Research Instruments
Since many dermatologists do use internet-connected personal computers for their practice, the initial data assembling consists of an exclusively electronic data based collection. All CRFs and questionnaires used in the registry are standardized, have been pre-tested in pilot studies and/or are well evaluated scales, developed in accordance with internationally accepted methodological standards of psychometrics.
The study group consists of several treatment groups, according to pharmaceutical products, substantially comparing patients (person years) from biological treatment group to a control group with similar characteristics but exposed to the non-biological systemic therapies or to surgery treatments.
The core data set of important variables, both physician and patient rated, will be collected in specific time points (see above) via web-based system that allows to capture the data to determine long-term effectiveness, patients reported outcomes, maintenance dosages, safety and predictors of response in HS treated with conventional and/or systemic treatment, and surgery. The web-based data collection ensures appropriate monitoring, storing and valid reviewing.
The establishment and operation of HSR will be in close cooperation with the participating pharmaceutical companies, whose product-related requirements of pharmacovigilance will be taken into account.
Analyses
The analyses will be made descriptively and reported as sequential time-series data and by subgroup tabulations, from which reports on safety and other outcomes will be generated at regular intervals.
Analyses will take into account switching from the group with systemic treatment to a biologic agent (and vice versa) as well as switching from one product of a treatment group to another.
During the course of the registry analyses will also be made based on a nested case-control design, i.e. “cases” with a certain outcome of interest will be compared with regard to differences in exposures variables (treatments) to matched “controls” in which this outcome hasn’t occurred.
Supervision and quality assurance
A scientific Advisory Board will supervise the planning, performance and analysis phase of HSR.
The Steering Committee also checks the annual figures at HSR and the transparency of contacts to the sponsors.
The Steering committee meets as needed and communicates otherwise by Email and by Telephone conferences.
The size of the panel is variable but should be limited for reasons of practicability. The current members are listed on page 3 of this protocol.
Quality assurance at the study centers
The objective is sufficient qualification of all participating centers in performing patient recruitment, determination of all outcome parameters, completing and correcting of CRFs and reliable organizational handling of the registry.
The quality of data recording at the individual centers is controlled by plausibility checks immediately on receipt of data. If data are of questionable quality, discussions will be held on site and measures to improve personnel performance will be implemented.
Description of plans for protecting human subjects
The Documentation Center will be financed by third-party support. Since no financing with public funds is to be expected in the foreseeable future, the required funds must be obtained primarily from the participating pharmaceutical companies. Financing and services will be regulated by bilateral contracts between HSR and the participating companies.
Authors: Dr. Florian Anzengruber, Vahid Djamei
