EPI3 Research Programme

Gérard DURU, PhD CYKLAD GROUP, Rillieux la Pape, France Expert of EPI-3 scientific Committee

Programme EPI-3(Etude Phamacoépidémiologique de l’Impact de santé publique de 3 groupes de pathologies)

Bruges, november 2015

Members Pr Bernard Bégaud-Président Pr Frédéric Rouillon Pr Didier Guillemot Dr Bernard Avouac Pr Jacques Massol Pr Gérard Duru Pr Anne-Marie Magnier

Research TeamEquipe Dr Lamiae Grimaldi, LASER

ANALYTICA Mme France Lert, INSERM* Pr Jacques Bénichou,

INSERM* Pr Michel Rossignol,

Université McGill* Pr Lucien Abenhaim, LASER

ANALYTICA

*LASER Consultants

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Scientific Committee EPI-3

Declaration of interest Laboratoires Boiron, France, sponsored this independant study

EPI3

The sponsor had no role in the design, management, data collection, analyses, interpretation, and writing of the manuscript or the decision to publish our findings

10 international publications in peer-reviewed journals have been published

Gérard Duru declares that he has no competing interests.

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Publications Benchmarking the burden of 100 diseases: results of a nationwide representative survey within general practices. Grimaldi-

Bensouda L, Begaud B, Lert F, Rouillon F, Massol J, Guillemot D, Avouac B, Duru G, Magnier AM, Rossignol M, Abenhaim L; EPI3-LA-SER Group. BMJ Open. 2011 Nov 14;1(2):e000215.

Characteristics of patients consulting their regular primary care physician according to their prescribing preferences for homeopathy and complementary medicine. Lert F, Grimaldi-Bensouda L, Rouillon F, Massol J, Guillemot D, Avouac B, Duru G, Magnier AM, Rossignol M, Abenhaim L, Begaud B; EPI3-LA-SER Group. Homeopathy, 2014 Jan;103(1):51-7.

Benchmarking clinical management of spinal and non-spinal disorders using quality of life: results from the EPI3-LASER survey in primary care. Rossignol M, Begaud B, Avouac B, Lert F, Rouillon F, Bénichou J, Massol J, Duru G, Magnier AM, Guillemot D, Grimaldi-Bensouda L, Abenhaim L. Eur Spine J. 2011 Dec;20(12):2210-6. doi: 10.1007/s00586-011-1780-z. Epub 2011 Apr 13.

Who seeks primary care for musculoskeletal disorders (MSDs) with physicians prescribing homeopathic and other complementary medicine? Results from the EPI3-LASER survey in France. Rossignol M, Bégaud B, Avouac B, Lert F, Rouillon F, Bénichou J, Massol J, Duru G, Magnier AM, Guillemot D, Grimaldi-Bensouda L, Abenhaim L. BMC Musculoskelet Disord. 2011 Jan 19;12:21.

Impact of physician preferences for homeopathic or conventional medicines on patients with musculoskeletal disorders: results from the EPI3-MSD cohort. Rossignol M, Begaud B, Engel P, Avouac B, Lert F, Rouillon F, Bénichou J, Massol J, Duru G, Magnier AM, Guillemot D, Grimaldi-Bensouda L, Abenhaim L; EPI3-LA-SER group. Pharmacoepidemiol Drug Saf. 2012 Oct;21(10):1093-101.

Physician practicing preferences for conventional or homeopathic medicines in elderly subjects with musculoskeletal disorders in the EPI3-MSD cohort. Danno K, Joubert C, Duru G, Vetel JM. Clin Epidemiol. 2014 Sep 26;6:333-41.

Management of upper respiratory tract infections by different medical practices, including homeopathy, and consumption of antibiotics in primary care: the EPI3 cohort study in France 2007-2008.Grimaldi-Bensouda L, Bégaud B, Rossignol M, Avouac B, Lert F, Rouillon F, Bénichou J, Massol J, Duru G, Magnier AM, Abenhaim L, Guillemot D. PLoS One. 2014 Mar 19;9(3):e89990.

Who seeks primary care for sleep, anxiety and depressive disorders from physicians prescribing homeopathic and other complementary medicine? Results from the EPI3 population survey. Grimaldi-Bensouda L, Engel P, Massol J, Guillemot D, Avouac B, Duru G, Lert F, Magnier AM, Rossignol M, Rouillon F, Abenhaim L, Begaud B; EPI3-LA-SER group. BMJ Open. 2012 Nov 22;2(6). pii: e001498.

Homeopathic medical practice for anxiety and depression in primary care: the EPI3 cohort study. Grimaldi-Bensouda L, Engel P, Massol J, Guillemot D, Avouac B, Duru G, Lert F, Magnier AM, Rossignol M, Rouillon F, Abenhaim L, Begaud B; EPI3-LA-SER group. Soumis BMC Family Practice, 2014.

Psychotropic drug utilization by patients consulting for sleep disorders in homeopathic and conventional primary care medical practice: the EPI3 cohort study. Grimaldi-Bensouda L, Engel P, Massol J, Guillemot D, Avouac B, Duru G, Lert F, Magnier AM, Rossignol M, Rouillon F, Abenhaim L, Begaud B; EPI3-LA-SER group. En préparation pour Evidence-based complementary and alternative medicine, 2014.

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Objectives of the EPI3 program

To assess the role played in France by homeopathy in primary care and its public health interest,

To describe and compare patients according to the practices (allopathic, homeopathic or mixed) selected by their general practitioners CROSS-SECTIONAL STUDY.

To assess the impact over one year of the various methods of treatment in three pathology groups representing a very important part of consultations in primary care:

Musculoskeletal Disorders (MSD). Upper Respiratory Tract Infections (URTI), Sleep disorders, Anxiety and Depression (SAD), THE THREE COHORT STUDIES.

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Evaluated outcomes

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MSD URTI SAD

Clinical evolution

Reduction 12,5% :EifelLequesneQuick Dash

Symptoms (7) resolved or greatly improved

HADS < 9PSQI = 0

Drugs consumption

(Yes/No)

NSAIDAnalgesics

AntibioticsAntipyretics

AntidepressantsPsychotropic drugs

Complications (Yes/No)

ChronicityThe start of a psychotropic drug treatment

Otitis media ou externa, Sinusitis

Tentative suicideUnintentional Injuries

Telephone questionnaire and recruitment of general practitioners A representative sample of GPs and their patients in primary

French healthcare 17 206 GPs were contacted (55 863 GPs in the national registry

of French GPs) GPs sampling was stratified according to their declaration of

prescription preferences categorised in three groups. GPs answered a telephone questionnaire in order to allocate them to one of these three groups (without the knowledge of objectives).

804 participating GPs : 196 GPs who prescribed conventionnal medicines only

(CM) 352 GPs with a mixed practice (Mx)  256 homeopathic GPs (Ho)

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The cross-sectional study

A one-day of consultation for each participating GP randomly selected

Collection of data directly at the GP’s office with a trained interviewer on site

8 559 included patients of which 6 379 by their gate keeper GP

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Collection of data directly at the GP’s office Waiting room : Consenting patients completed a self-administered questionnaire: Information on socio-demographics, lifestyle, occupation History of hospitalization and number of GP consultations in the past year. Quality of life

GP’s office : Eligible patients were invited to participate for the cohort study and GP completed a medical questionnaire for those who accept. Diagnostics Prescriptions that day

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3 cohort studies

Patients who participated in the cross-sectional study

N = 8559

Patients who filled out a MSD

medical questionnaire

N = 1917

Patients who filled out a URTI

medical questionnaire

N = 906

Patients who filled out a SAD

medical questionnaire

N = 1694

Patients who participated in a MSD interview at

T0 N = 1153

Patients who participated in a URTI interview at

T0 N = 518

Patients who participated in a SAD interview at

T0 N = 710

General Scheme of EPI-3 Program

Retrospective data collection (cross-sectional study )

Inclusion of patients

Prospective follow-up by telephone interview (3 cohort studies)

Collection of data from February 2007 to August 2009

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12 months <72 h 1 month 3 months 12 months

The cross-sectional study

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EPI-3EPI-3

The observed prescription of homeopathic medicinesRemender : the size of the GPs sample is 804

Homeopathic prescription the day of the consultation (%)

CM M Ho N=196 N=352 N=256

No homeopathic prescription 92,4 67,1 6,3

≥ 1 homeopathic prescription this day 6,6% 32,9% 93,7%

One 5,6 15,4 5,1More than two 1,0 17,5 88,6

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Among patients of homeopathic GPs, we notice : More women Higher level of education Lower tobacco consumption Lower body mass index (BMI)

Characteristics of patients by type of practice of their treating GP (n=6379 which is the regular GP)

14* Differences with GP-CM statistically significant (p< 0,05)

Patients attending GP-Ho exhibited more frequently Osteoarthritis and joint diseases (B) OR=1.29; IC:(1.07-1.56) Anxiety-depressive disorders (C) OR=1.38; IC:(1.15-1.65) Dermatological diseases (I) OR=1.40; IC: (1.02-1.92) But fewer for acute respiratory diseases (A)

Prevalence of 14 broad ICD* diagnostics according to the type of practice

CM Ho Mx

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* International classification of diseases: A : Diseases of the respiratory system, B : Diseases of the musculoskeletal system, C : Anxiety, depression and sleep disorders, D : Cardiovascular diseases, E : Diabetes, thyroid gland & other endocrine disorders, F : Diseases of the digestive system, G : Diseases of the genitourinary system, H : Diseases of the nervous system, head & neck, I : Skin and subcutaneous tissue diseases, J : Bacterial, viral and parasitic systemic diseases, K : Injury and poisoning, L : pregnancy, post-partum, newborn and childcare visit, M : Administrative and preventive motives, medical results, N: Other diseases (cancer and infrequent diseases)

Quality of life SF-12

Odds ratios adjusted on gender, age, education and comorbidities.

Patients attending GP-Ho are: in better physical health (a slightly higher (better)) physical component score more likely to express a psychological malaise (a slightly lower (worse)) mental component score

  CM Mx HoPhysical score

Mean (SD) 45,2 (11,1) 45,2 (11,4) 47,2 (10,6)

OR (CI 95%)*

<1st Quartile Ref 1,15 (0,98-1,30)

0,81 (0,68-0,95)

Mental scoreMean (SD) 41,6 (10,9) 41,5 (10,8) 40,9 (10,5)

OR (CI 95%)*

<1st Quartile Ref 1,08 (0,95-1,24)

1,21 (1,04-1,42)

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The Complementary and Alternative Medicine Beliefs Inventory (CAMBI)

Odds ratios adjusted on gender, age and education

Patients consulting GP-Ho are: More open to natural treatments Value further their participation in care Have a more holistic approach to health

  CM Mx Ho

OR (CI 95%)*

>3rd Quartile Ref 1,22 (1,08-1,37)

2,05 (1,79 – 2,36)

OR (CI 95%)*

>3rd Quartile Ref 0,91 (0,81 – 1,02)

1,52 (1,33 – 1,74)

OR (CI 95%)*

>3rd Quartile Ref 1,13 (1,00-1,28)

3,19 (2,77 – 3,66)

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The Logitudinal study

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EPI-3EPI-3

Results Musculoskeletal pain and Disorders (MSD)

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Clinical evolution : scales on functional status NSAID consumption, Analgesics Complications : progress from non-chronic MSD at inclusion to chronic MSD and the start of psychotropic drug treatment

N=1 153 (changes slightly depending on missing data in the analyzes)

Evolution of DMS functional scales

10

20

30

40

Inclusion 1 Month 3 Month 12 Month

CMMx

Ho

Non-Chronic at inclusion(N=514)

Chronic at inclusion(N=615)

* Combined standardized over 100: EIFEL, Quick Dash, Lequesne

CMMxHo

10

20

30

40

Inclusion 1 Month 3 Month 12 Month

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Ho patients showed better functional scores on average at baseline (Lequesne et Quickdash)

Regarding MSD progression, non-chronic patients were comparable to chronic patients across the three PPP groups.(ANOVA: p>0,5).

NSAID and analgesics consumption

CM(N=272)

Mx(N=510)

Ho(N=371)

Odds ratios (I.C. 95%)*Non-chronic MSD

AINSRef

0,78(0,50 – 1,22)

0,58(0,35 – 0,95)

Analgesics 0,53(0,35 – 1,18)

0,69(0,33 – 1,45)

 Chronic MSD

NSAIDsRef

0,81(0,52 – 1,24)

0,56 (0,35 – 0,90)

Analgesics 0,54(0,27 – 1,08)

0,40(0,20 – 0,82)

Probability of consuming NSAID or analgesics (12 months of follow-up) (N=1153)

21* Adjusted for age, gender, functional score at inclusion and propensity score

Complications

The rate of progressing from non-chronic MSD at inclusion to chronic MSD did not differ between the three groups.

The occurrence of anxiety and depressive disorder during follow-up, the frequency of use of psychotropic drugs were comparable across the three groups (For Ho vs CM : OR= 0.96; IC 95% : 0.53-1.75).

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Results Upper Respiratory Tract Infections (URTI)

Clinical evolution: symptoms’ resolution Antibiotics consumption, antipyretic Complications: otitis media/externa and sinusitis

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N=518 (changes slightly depending on missing data in the analyzes)

EPI-3EPI-3

Probability of URTI resolution

CM(N=165)

Mx(N=203)

Ho(N=150)

Resolution of the URTI symptoms resolved or greatly improved

Odds ratio (I.C.95%)*

Ref 1.10 [0.63–1.91]

1.16 [0.64-2.10]

Probabilities of URTI symptoms’ resolution were comparable by type of medical practice.

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* Adjusted for age, gender, smoking (adults), number of URTI symptoms, diagnosis at inclusion URTI in previous 12 months and comorbidities.

Antibiotics and antipyretics consumption among types of medical practice

0.43 0.54

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* Adjusted for age, gender, smoking (adults), number of URTI symptoms, diagnosis at inclusion URTI in previous 12 months and comorbidities.

HoMxCM (ref.)

Antibiotics Antipyretics

Complications

CM(N=165)

Mx(N=203)

Ho(N=150)

Potentially associated infections (At least one declaration of otitis/sinusitis in 12 months)

Odds ratio (I.C. 95%) *

Ref. 0.88 [0.46–1.71]

1.70¶

[0.90–3.20]

Infection rates (sinusitis and otitis media, otitis externa) are close with an adjusted relative risk slightly higher in the Ho group compared to the CM group, a difference not statistically significant.

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* Adjusted for age, gender, smoking (adults), number of URTI symptoms, diagnosis at inclusion URTI in previous 12 months and comorbidities.

Crude rates for CM:16.9%, Ho:17,7%.

Results sleep disorders, anxiety and depression (SAD)

Clinical evolution : improvement on HADS scale Psychotropics drugs consumption Complications: injuries and suicide attempts

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N=710 (changes slightly depending on missing data in the analyzes)

EPI-3EPI-3

Evolution of sleeping disorders

CM(N=84)

Mx(N=119)

Ho(N=143)

Odds ratio (I.C.95%)*

Sleeping disorder persisting at three months

Ref.0,94

(0,56 – 1,57)0,72

(0,42 – 1,22)

Evolution of SD (sleep disorders resolution on Pittsburg scale) did not differ significantly among types of medical practice.

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* Adjusted for age, gender, education, alcohol consumption, BMI, Smoking, sleeping disorder at inclusion, the regular treating GP.

Psychotropic drugs consumption in the 12 month follow-up by type of medical practice

CM(N=84)

Mx(N=119)

Ho(N=143)

Odds ratios (I.C. 95%)*Psychotropic drug for

sleep disordersRef

0,67(0,39 – 1,16)

0,25(0,14 – 0,42)

Psychotropic drug for severe sleep disorders

at inclusion

0,67(0,37 – 1,23)

0,21(0,12 – 0,37)

Probability of consuming psychotropic drug for sleep disorders (12 months of follow-up) was significantly lower in the GP-Ho group compared to the GP-CM group. This effect was not modified by the severity of SD at baseline.

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* Adjusted for age, gender, education, alcohol consumption, BMI, Smoking, sleeping disorder at inclusion, the regular treating GP.

Severity of sleeping disorders defined as reporting one or more of the following from the PSQI: problems staying awake during activities once a week or more or lack of enthusiasm (somewhat or a very big problem).

Complications Lower rate observed in the GP-Ho group compared to GP-CM

group but not statistically significant.

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CM(N=84)

Mx(N=119)

Ho(N=143)

Odds ratio (I.C.95%)*

Traumatics events(Any injury resulting from a fall, motor vehicle collision, sport, or occupation.)

Ref.0,33

(0,10 – 1,03)0,57

(0,21 – 1,52)

Results, anxiety and depression

Results on anxiety and depression match those of sleeping disorders.

Publication under review

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General conclusion

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The therapeutic management by homeopathic GPs had a real interest to public health in studied pathologies in France, especially:

Clinical evolution of patients seen by was similar to that of others patients.

Patients of homeopathic GPs consume significantly less targeted conventional medicines . However, this consumption is not null and seems to follow a consistent distribution in terms of pathologies.

The choice of a regular* homeopathic GP is not associated with a loss of therapeutic opportunity for the patient..

*designated “treating physician” according to French regulation

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Thank you AllThank you All