Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04603313 |
| Other study ID # |
38RC18.073 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 15, 2019 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
May 2023 |
| Source |
University Hospital, Grenoble |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The increase in bacterial resistance and the overuse of antibiotics have led health
authorities to propose incentives for the proper use of antibiotics. Among these measures,
the introduction of referring physicians for antibiotic therapy and tele-advisory devices for
infectious diseases have shown positive effects on antibiotic prescriptions in hospitals.
Today, an increase is observed in the consumption of antibiotics linked to ambulatory
prescriptions.
The objective of the project is to deploy tele-advice devices for general practitioners and
to evaluate the effects on ambulatory antibiotic dispensing.
AIRBUS-ATB is a prospective, multi-center, population-based, interrupted time-series
observational study with a control group with 12 points before and 24 points after the
deployment of the intervention in voluntary territories.
Description:
1. Current knowledge on the problem
The increase in bacterial resistance and the overuse of antibiotics have led health
authorities to propose incentives for the proper use of antibiotics. Among these
measures are public awareness campaigns, the establishment of antibiotic reference
materials and the development of indicators of appropriate use in health facilities.
In response to these issues, the infectiology teams have developed cross-cutting
activities to improve antibiotic prescribing in their healthcare institutions: drafting
and implementing clinical practice recommendations; initial and continuing training of
prescribers in the proper use of antibiotics; evaluation of practices for the management
of infectious diseases; organization of collaborations with the CLIN, microbiology
laboratories and pharmacy; monitoring and analysis of antibiotic dispensing, monitoring
and analysis of bacterial resistance.
Some teams have set up prescription support systems to meet the growing demand from
non-infectious disease clinicians and to satisfy the criteria of the Composite Indicator
of Antibiotic Use (ICATB 2), which relates to "access to antibiotic therapy advice". In
2000, the cross-disciplinary infectiology team at Grenoble Alpes University Hospital set
up a "Mobile Infectiology Consultation (MIC)" based on a cell phone medical service
available 24 hours a day, 7 days a week. This team carried out an analysis of all the
informal consultations treated by this "hotline" during 2008. 7863 advice was given
during the study period; 37.3% of them within the University Hospital Center to adapt or
start antibiotic therapy. This activity has developed significantly and is now well
established in France in the hospital environment. The Grenoble team conducted a new
evaluation in 2016 and recorded nearly 16,000 calls per year (publication in progress).
Studies of intra-hospital infectious disease teleadvisory services have shown that
compliance with infectious disease advice reduces the consumption of anti-infectives and
improves the prognosis of hospitalized patients. Thus Sellier et al reported the results
of a prospective study carried out on 621 patients benefiting from infectious disease
counseling. Adherence to the advice given was good 88.2% (548/621). When counseling was
followed clinical improvement at D3 was more frequent (60.7% versus 43.9%, p=0.01) and
the median duration of hospitalization was 3 days shorter (20 days versus 23, p=0.03).
Adherence to telephone advice was comparable to that of formal advice given during a
consultation, out of a series of 627 consecutive advice sessions reported by the same
team. These results are supported by other studies that highlight the positive impact of
informal consultation with infectious disease specialists on the management of
inpatients, particularly in intensive care units.
Between 2000 and 2004, the consumption of antibiotics decreased in France by 18.4%. Then
it went up and down between 2005 and 2008. Since 2010 there has been a recovery trend
that is confirmed every year (+5.9%). The growth in consumption appears to be much
higher for outpatient prescriptions than for hospital prescriptions (90% versus 10%).
A more recent decree (2015), specifying the role of referring physicians as well as axis
3 of the report "Saving antibiotics" recommended developing infectious disease advice
for primary care physicians (general practitioners).
Experiences concerning tele-advice to general practitioners are, however, rarer than
intra-hospital experiences and have been little studied. In Grenoble, the hotline was
opened from the outset to general practitioners and practitioners outside the university
hospital. More than half of the advice provided (56%) by this team concerned them.
Requests were more often handled by telephone when they came from general practitioners
(89% versus 46% for intra-hospital requests). The reasons for calling the hotline from
GPs were significantly different from those of hospital phisicians. Indeed, in this
study, intra-hospital requests concerned the management of osteoarticular (14%), skin
and soft tissue (9%), or pulmonary (11%) infections; whereas GPs were more often
concerned about long-term fevers or unexplained inflammatory syndromes (11%).
Marquet et al. recently described the activity of Medqual, a network of 20 infectious
diseases specialists in the Pays de Loire region. During the 5 days studied, this
network had received 386 telephone calls, most of which (81%) came from physicians in
the same hospital. Of these, 7.7% were from other hospitals and 11.3% from private
practice. 6% of the calls resulted in formal consultations and 5.5% in hospitalizations.
68.7% of responses could be given by telephone.
Bal et al questioned 284 general practitioners using an infectiology hotline. 97.9% of
them were satisfied with the hotline. They said they used this service to improve
patient care (96.5%) and appreciated the speed of access (86.3%). Their questions mainly
concerned antibiotic treatments (66.2%) but also diagnostic aids (46.5%) and requests
for consultations or hospitalizations (29.6%). The latter requests are particularly
important to optimize the patient's journey.
Teleconsulting in infectious diseases therefore seems to meet a need by allowing rapid
recourse to a physician specialized in infectious diseases.
The objective of our project is to extend the teleconsulting activities for general
practitioners to new territories by teams of volunteer infectious disease specialists.
The investigators wish to evaluate the effects of this activity on the evolution of
antibiotic dispensing and on the prescribing practices of general practitioners.
Outpatient dispensing of antibiotics will be analyzed from the dispensing of drugs
registered by the Assurance Maladie, through the study of the general sample of
beneficiaries (EGB) at the 100th of the protected population.
Advice for general medicine will be recorded on an ad hoc database, the AIRBUS database.
This system, which is independent of hospital information systems, should enable
referring infectious diseases specialists to record in real time their out-of-hospital
tele-advice activity.
The originality of the project lies first of all in the target of the intervention. Up
to now, the devices to assist in the prescription of antibiotics have been intended for
hospital services within the framework of referring physicians in antibiotic therapy and
mobile infectiology consultations. The deployment of tele-advisory devices in infectious
diseases to primary care medicine is an innovation whose usefulness has yet to be
demonstrated.
The other element of originality lies in the choice of an objective judgment criterion:
the consumption of antibiotics on an outpatient basis. The investigators are aware that
the number of treatments for which specialized advice will be provided will be minimal
compared to the mass of antibiotic prescriptions in ambulatory medicine. However, the
investigators believe that the advice given by infectious diseases specialists will have
an educational effect likely to induce changes in practices and changes in dispensing by
halo effect. This is why the investigators suggest to collect the judgement criteria
over a long period (3 years) and to collect it in the same way in territories not
covered by a tele-advice system.
This work will also make it possible to better understand the needs of general
practitioners in terms of assistance in the management of infectious pathologies and to
adapt the offer of continuing education in this specialty.
In addition, the implementation of teleconsulting devices by hospital specialists
constitutes a new model of relationship between professionals that could contribute to
improving collaboration between primary care medicine and hospital specialist medicine.
2. Research hypotheses
It can be hypothesized that an infectious advice hotline for general practitioners could
have the same type of effects on the consumption of anti-infectives and the clinical
evolution of patients as intra-hospital advice. This is suggested, for example, by a
recent study by Meeker's team which describes the importance of behavioural
interventions on the quality of antibiotic prescriptions in general medicine. In
addition to the positive impact on patient care through real-time response and thus
immediate action on therapeutic decisions, this advice would allow additional 'hands-on'
training of the doctors involved in city infectiology and the correct use of
antibiotics, through advice given in concrete situations (halo effect). Its impact would
also be measurable on care trajectories (e.g. saving on medical consultations, avoiding
emergency visits).
If our hypotheses are confirmed, the infectious diseases tele-advice system could be
deployed in other French healthcare territories. In the long term, it is hoped that this
system will have a beneficial impact on the consumption of antibiotics and on the
development of bacterial resistance.
3. Research objectives and endpoints
3.1. Main objective
To determine the effects of the deployment of an infectious disease tele-advice system
for general practitioners on the overall and class dispensing of antibiotics in
ambulatory medicine compared to the absence of specific intervention.
3.2 Secondary objectives
- To qualify the needs of general practitioners in infectiology for advice.
- To study the responses provided by the infectious disease referents (type of
response, time spent).
- To study the compliance of general practitioners with this advice.
- To study the impact of advice on the patient's care pathway.
- To study the opinion of requesting GPs on the device.
4. Study description
4.1 Study design
This is a prospective, multi-center, population-based, interrupted time-series
observational study with a control group with 12 points before and 24 points after the
deployment of the intervention in voluntary territories.
4.2 Intervention
The intervention consists of setting up in each voluntary center an infectious disease
tele-advice system available to general practitioners via a dedicated cell phone line.
GPs will receive information when the telecounseling system is set up in their practice
health territory.
4.3 Population
The primary study population will consist of health insurance-registered systemic
antibiotic dispenses for patients present in the EGB for 36 months: 12 months prior to
deployment of the telecounseling devices and 24 months post-deployment.
- The experimental group will be made up of all metropolitan departments covered by
an infectious disease tele-advice system open to general practitioners; 13
metropolitan departments will be concerned.
- The control group will be made up of all the metropolitan departments not covered
by an infectious disease tele-advice system open to general practitioners; 82
departments will be involved. Few centers have set up a response system accessible
to general practitioners. For those centers that are available, the number of
notices is very low.
Number of planned observations to be recruited:
A study of ambulatory dispensing of systemic antibiotics recorded in the SNIIRAM
database in 2015 in the Rhône-Alpes region found a consumption of 64,165,140 Defined
Daily Doses (DDD) for 6,510,561 inhabitants, i.e. 27 DDD/1000 inhabitants per day.
By extrapolating these data to the Simplified General Sample of Beneficiaries (1/97th of
the SNIIRAM database) for metropolitan France, it can be estimated that the analysis
will cover 70 to 80 million DJD per year, i.e. 210 to 240 million DJD over 3 years. The
unit of analysis will be the consumption per month and per territory, i.e. 96x36 = 3456
units month-department.
The secondary population of the study will be constituted by the opinions requested by a
general practitioner from an infectiological tele-advice system. The opinions requested
during 12 months, from September 2018 to August 2019 will be recorded in the AIRBUS
database.
Number of planned observations to be recruited
Based on a study carried out in 2016 in 5 departments of the Rhône Alpes region, it can
be estimated that each center should give about 30 pieces of advice per month to the
general practitioners of their department. Therapeutic advice represents 40% of the
advice given to GPs. The investigators can estimate the total number of counsels
expected for the study at 4100 in one year, of which about 1500 will be followed up on
D7.
4.4 Data collection
Infectiological warnings
All requests for infectiological opinions made by general practitioners will be recorded
in the AIRBUS database, a computer application developed on the Voozanoo platform
(Epiconcept) by the SPILF. The platform is accessible via the Internet and is authorized
to host medical data.
Each participating antibiotic referent will have an identifier and a personal code
allowing him/her to record his/her opinions and to access his/her own database. For each
request, the referring physician will record, with the agreement of the requesting
physician :
- the name of the requesting general practitioner and his or her telephone number,
- the reason for the appeal (advice for a patient, general question) ;
- the characteristics of the patient (age, sex, diagnosis)
- the date and time of the call ;
- the identity of the sponsoring physician;
- the modalities of the response (consultation, telephone, e-mail, other);
- the notion of hospitalization following the notification (yes, no, in infectiology,
emergency, in another department);
- the notion of carrying a multi-resistant bacterium (BMR);
- the time spent for counseling (in minutes, including application filling);
- the response given by the infectiologist (starting an anti-infectious treatment, no
modification of the current treatment, optimization of the treatment by oral relay
or de-escalation or shortening the duration or changing the dose, stopping the
antibiotic treatment, no treatment necessary, diagnostic assistance).
The recording of opinions may be carried out by the participating physician or by a
clinical research assistant. The application will also be available on a tablet or
smartphone.
Follow-up of notifications at D7
For opinions involving therapeutic advice (initiation or modification of antibiotic
therapy) an ARC will contact the requesting GP 7 days (± 2 days) after the opinion.
During a telephone interview, he will collect the following information:
- the prescriptions made by the physician, in order to assess compliance with the
advice.
- the evolution of the patient if the doctor has this information. This evolution
will be coded according to previously defined criteria (cure, decrease in fever,
decrease in the intensity of symptoms, decrease in a possible inflammatory
syndrome) ;
- basic information on the doctor's mode of activity
- the GP's opinion on the device (usefulness, satisfaction, influence on practices,
proposal(s) for improving the system) Responses will be collected on a 4-way Likert
scale. These follow-up data will be recorded in a computer application developed
for this purpose on the Voozanoo platform.
Antibiotic dispensing
Antibiotic dispenses will be tracked using monthly extractions from the SNIIRAM's
simplified EGB database (EGBs) provided by the National Institute of Health Data (INDS).
The extraction will concern 1/97th of all systemic antibiotic dispensations (oral or
injectable) registered by the health insurance (EGBs database) for 3 years. For each
dispensation the International Nonproprietary Name (INN) of the antibiotic, the quantity
dispensed, the date and place of dispensing and the identity of the prescriber will be
collected. These dispensations will be classified by month, department and therapeutic
class. The dispensations will be expressed in defined daily doses (DDD) in relation to
the number of inhabitants per department present in the EGB.
Follow-up of the dispensations will begin in the year preceding the intervention and
will continue during the study year and one year after, for a total of 36 months.
4.5 Statistical analysis
Analysis plan
A Statistical Analysis Plan (SAP) will be developed before the database is frozen,
reviewed by the coordinating investigator and an independent statistician. This plan
will outline the principles guiding the analysis, including :
- The analysis sample and any subgroups ;
- the frequentist approach to the analysis
- The statistical significance level and the level of confidence intervals ;
- The possible adjustment of the p-value to take into account the multiplicity of
tests;
- The descriptive statistics used for the qualitative and quantitative variables; and
- The possible transformations of the variables ;
- Variables created or recoded;
- The association measures used;
- The univariate and multivariate analysis strategy. The SAP will include an explicit
detailed description of the univariate and multivariate analyses presented in the
final statistical report (FSR). Unplanned analyses in the SAP, either exploratory
or confirmatory, are possible. They will appear as such in the FSR and manuscripts
submitted for publication.
Analysis of the main judgment criterion.
Antibiotic consumptions extracted from the SNIIRAM database will be analyzed with the
SAS software. They will be expressed in Defined Daily Doses (DDD) per 1000 inhabitants
per day.
Antibiotic dispensations extracted from the EGBs database will be analyzed with SAS
software. They will be expressed in Defined Daily Doses (DDD) per 1000 inhabitants per
day. The data will be analyzed using interrupted time series. The secular trend of
dispensing will be modeled before the intervention and then the modifications of this
trend will be compared between territories covered and not covered by the intervention
by a test of the first-order interaction between time and type of territory. Seasonality
will also be modelled using a 12-order moving average and the autocorrelation of
residuals using the ARIMA model. The investigators will use the Box jenkins approach and
in particular the autocorrelation and partial autocorrelation functions to develop the
ARIMA model. The analysis will cover all antibiotic dispensing and dispensing of the
major classes of antibiotics.
Analysis of notices
The statistical unit is the advice given by the infectiologist. The test sample will
consist of all the opinions included. A flow chart in accordance with the CONSORT/STROBE
transparency recommendations will present the number of test specimens.
The characteristics of the opinions will be summarized by the usual descriptive
statistics: number and percentage for qualitative variables and mean and standard
deviation (or median and 25th-75th percentiles, in case of asymmetric distribution) for
continuous quantitative variables.
In univariate analysis, the characteristics of the opinions associated with compliance
will be analyzed using the Chi-square test, replaced by Fisher's exact probability in
case of expected numbers below 5, for the qualitative variables, and the Student test,
replaced by the non-parametric Wilcoxon test, in case of deviation from normality, for
the continuous quantitative variables. The investigators will identify characteristics
independently associated with compliance using a multivariate logistic regression model.
To prevent over-fitting of the model to the data, the covariates introduced in the
multivariate model will be selected a priori based on the literature and the team's
previous publications in the field. Because of the non-independence of opinions from the
same infectiologist, the investigators will use a two-level randomized model
(opinion/infectiologist). In a further analysis, the investigators will develop a
three-level model (opinion/infectiologist/institution). The adherence analysis will
include the complete observations for the dependent variable and the independent
covariates (casewise analysis). To ensure the robustness of the results, the
investigators will repeat this analysis using a multiple imputation method for missing
data.
The analysis of the other criteria will be exploratory. As such, no adjustments to the
degree of statistical significance will be made. Statistical comparisons will be
performed using the Student t test or the non-parametric Wilcoxon test for continuous
quantitative variables and using the Chi-square test or the Fischer's exact probability
for qualitative variables.
Point estimates will be framed by a 95% confidence interval. The statistical
significance level will be set at 5%, in bilateral situations. The analyses will be
performed with Stata SE software (version 15.0 or later, StataCorp, College Station, TX,
USA).
5. Ethical considerations
The study does not involve direct action on patients; no nominative information will be
collected. The study involves prospective collection of data from healthcare
professionals: infectious disease physicians and general practitioners who are
applicants. It therefore complies with type 3 of the Jardé law: "non-interventional
research that does not involve any risk or constraint, in which all acts are performed
and products are used in a usual manner".
An information sheet will be distributed to each physician who is a member of a
participating infectiology team and the physician's consent will be obtained in writing
at the opening of the center. Information will be given by telephone to each requesting
physician and his/her consent will be collected orally for the recording of the
notification data and for the follow-up of the notification at D7.
The protocol and the information documents of the doctors will be submitted for opinion
to a committee for the protection of persons drawn by lot.
6. Auditing
Monitoring of study processes and documents will be conducted by personnel designated by the
Direction de la Recherche Clinique et de l'Innovation (DRCI) at Grenoble university hospital.
