Clinical Trials in Russia Through Patients’ Eyes

Results of a multicenter study in the Russian Federation

Study: Face2Face

Clinical trials as seen by physicians

Clinical trials as seen by patients

Objective of study

Evaluate the expectations, motivation and experience of patients participating in clinical trials (CTs)

Face2Face

Multicenter cross-sectional study

Tomsk

Novokuznetsk

Khanty-Mansiysk

Saint Petersburg

Pyatigorsk

Population Studied

1. Under the protocol, the experience of participation in the study was

defined as the signing of informed consent and carrying out all planned procedures of at least one visit to a clinical trial site, accredited by the Russian Ministry of Health.

2. Patients who are currently involved in clinical trial or were involved in the past included

70% currently involved

30% Involved in the past

58% participated in CT

for the first time

Respondents’ characteristics

n=184

n=79; 43%

OR 1.33 (95%CI 0.93-1.90)

age 57.7±18.4 yrs

n=105; 57%

56.8±19.9 yrs 58.3±17.2 yrs

56% 39% 60% 68%

married education retired income10-20 thousand

rubles per capita

Decision-making and motivation to participate

Decision-making

«Who did you advise with about participation in a clinical trial?»

• attending physician – 47.3%, n=88

• independently – 24.7%, n=46

• family members- 15.1%, n=28

• friends and acquaintances – 2.7%, n=2.7

Factors affecting the willingness to participate in a clinical trial

Factor Average score

Monitoring by professional medical staff 3.72±1.00

Regular monitoring of my condition 3.66±0.98

Better medical care 3.62±1.00

Free treatment 3.61±1.06

An opportunity to have additional medical examinations 3.50±1.03

Obtaining new information about my disease 3.48±1.03

Having the results of the study upon its completion 3.36±1.08

To be beneficial to the society 3.20±1.03

Acquisition of new data about researched drug 3.14±1.19

Knowing that I can stop participating at any time 3.08±1.13

"What are the most important factors for you when deciding to participate in a clinical trial?". Each factor was rated on a five-point scale, where 1 – “not important”, 2 –“Slightly important”, 3 – “Moderately important”, 4 - "very important" and 5 –“extremely important”

Factors with adverse effect on willingness to participate in a clinical trial

Factor Average score

Risk of side effects 3.01±1.27

Study of new medication 2.68±1.21

The risk of getting into placebo group 2.64±1.34

The necessity for regular visits to the hospital 2.43±1.20

Necessity of medical examinations and procedures 2.41±1.21

The necessity for regularly filling diaries and forms 2.22±1.17

"What factors were important and negatively influenced the interest in participating in the study?". Each factor was rated on a five-point scale, where 1 – “not important”, 2 –“Slightly important”, 3 – “Moderately important”, 4 - "very important" and 5 –“extremely important”

• According to the patients, when deciding to participate in CT the most important factors for the patients were: monitoring by professionals, regular monitoring of the condition, better medical care, and free treatment.

• Most significant factors with adverse effect were the risk of side effects, study of new medication and the risk of getting into the placebo group.

• When interpreting these results, it is highly probable that the findings reflect the specificity of the clinical trial and its difference from routine clinical practice, which is true all over the world, including the Russian Federation. In general, the clinical trials are carried out by highly qualified specialists in accordance with the principles of GCP, which involves regular monitoring of the patient's condition. These surroundings allow patients to perceive medical treatment in a clinical trial as of better quality and gives sense of feeling safe and secure. At the same time patients in our study were aware of the risks of participation. They critically evaluate the likelihood of actually getting the placebo treatment and are ready for higher organizational and clinical load in comparison to ordinary practice.

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Informed consent

Acquaintance with IC

44% independently

36% assistance

of researcher

20% read

by researcher

68% in clinic

32% at home

5.46±11.74 hours average

3.10±9.26 together with

researcher

8.63±13.90 independently

Acquaintance with IC

Parameter Researcher +

(n=96)

Researcher -

(n=76) p/OR

Age 58.50±18.02 52.72±17.75 0,030

Gender

(female/male) 52.1%/47.9% 57.9%/42.1%

OR 0.79

(95% CI 0.43-1.45)

Education

(secondary/higher education) 43.8%/34.4% 34.7%/44.0%

OR 0.79

(95% CI 0.81-3.21)

Martial status

(married/widowed) 58.3%/22.9% 56,0%/16,0%

OR 0.73

(95% CI 0.63-1.72)

Social status

(retiree/labor worker) 67.0%/13.8% 43,4%/10,5%

OR 1.18

(95% CI 0.44-3.12)

Income

(10-15/15-20 thousand robles) 43.8%/25.0% 34.2%/30.3%

OR 1.55

(95% CI 0.73-3.29)

Currently participating in CT

(yes/no) 74.2%/25.8% 52.0%/48.0%

OR 2.65

(95% CI 1.39-5.08)

First experience in CT

(yes/no) 69.6%/30.4% 45.2%/54.8%

OR 2.77

(95% CI 1.46-5.26)

Finished at least 1 CT?

(yes/no) 92.7%/7.3% 95.4%/4.6%

OR 0.61

(95% CI 0.14-2.66)

Number of CTs participated 1.82±1.81 1.94±1.21 0.036

Factors affecting the willingness to participate in a clinical trial

Factor Researcher

+

Researcher

-

р

Monitoring by professional medical staff 3.55±0.94 4.01±0.90 0.002

Regular monitoring of my condition 3.52±1.01 3.87±0.90 0.040

Better medical care 3.49±0.94 3.83±1.06 0.020

Free treatment 3.51±1.05 3.80±1.02 0.069

An opportunity to have additional medical examinations 3.48±1.02 3.67±0.99 0.224

Obtaining new information about my disease 3.36±1.05 3.65±1.00 0.094

Having the results of the study upon its completion 3.27±1.06 3.47±1.11 0.235

To be beneficial to the society 3.12±1.03 3.26±1.09 0.490

Acquisition of new data about researched drug 3.18±1.13 3.16±1.23 0.796

Knowing that I can stop participating at any time 3.02±1.11 3.28±1.12 0.154

"What are the most important factors for you when deciding to participate in a clinical trial?". Each factor was rated on a five-point scale, where 1 – “not important”, 2 –“Slightly important”, 3 – “Moderately important”, 4 - "very important" and 5 –“extremely important”

Factors with adverse effect on willingness to participate in a clinical trial

"What factors were important and negatively influenced the interest in participating in the study?". Each factor was rated on a five-point scale, where 1 – “not important”, 2 –“Slightly important”, 3 – “Moderately important”, 4 -" very important" and 5 –“extremely important”

Factor Researcher

+

Researcher

-

р

Risk of side effects 2.87±1.28 3.33±1.17 0.024

Study of new medication 2.65±1.23 2.93±1.11 0.085

The risk of getting into placebo group 2.51±1.25 3.03±1.34 0.022

The necessity for regular visits to the hospital 2.34±1.16 2.66±1.24 0.108

Necessity of medical examinations and procedures 2.42±1.23 2.52±1.18 0.620

The necessity for regularly filling diaries and forms 2.13±1.17 2.46±1.18 0.061

Complexity of IC

«How difficult was it for you to understand the text of informed consent?»

not

difficult

slightly

difficult moderately

difficult

very

difficult extremely

difficult

1.70±0.81

«After acquaintance with the informed consent how has your interest to participate changed?»

significantly

lost interest

lost interest not changed increased extremely

increased

3.37±0.87

Complexity of IC

Parameter Easy

(n=83)

Difficult

(n=92) p/OR

Возраст 53.25±17.79 58.72±18.02 0.021

Age 61.5%/38.5% 48.9%/51.1%

OR 1.67

(95% CI 0.91-3.04)

Gender

(female/male) 37.8%/47.6% 41.3%/30.4%

OR 0.59

(95% CI 0.30-1.16)

Education

(secondary/higher education) 51.2%/17.1% 62.0%/21.7%

OR 1.05

(95% CI 0.48-2.32)

Martial status

(married/widowed) 51.2%/22.0% 60.9%/11.0%

OR 0.42

(95% CI 0.17-0.99)

Social status

(retiree/labor worker) 35.0%/31.3% 44.6%/24.0%

OR 0.60

(95% CI 0.29-1.26)

Income

(10-15/15-20 thousand robles) 60.8%/39.2% 68.1%/31.9%

OR 0.72

(95% CI 0.39-1.36)

Currently participating in CT

(yes/no) 56.3%/43.7% 60.2%/39.8%

OR 0.85

(95% CI 0.46-1.57)

First experience in CT

(yes/no) 96.9%/3.1% 91.7%/8.3%

OR 2.82

(95% CI 0.59-14.49)

Finished at least 1 CT?

(yes/no) 1.89±1.77 1.87±1.34 0.201

Factors affecting the willingness to participate in a clinical trial

Factor Easy Difficult р

Monitoring by professional medical staff 3.84±0.97 3.67±0.92 0.209

Regular monitoring of my condition 3.75±1.01 3.58±0.97 0.305

Better medical care 3.77±1.02 3.52±0.97 0.108

Free treatment 3.69±1.07 3.61±1.00 0.645

An opportunity to have additional medical examinations 3.65±0.98 3.47±1.03 0.348

Obtaining new information about my disease 3.66±0.98 3.29±1.08 0.043

Having the results of the study upon its completion 3.54±1.11 3.17±1.05 0.030

To be beneficial to the society 3.28±1.03 3.10±1.07 0.321

Acquisition of new data about researched drug 3.25±1.23 3.07±1.12 0.392

Knowing that I can stop participating at any time 3.08±1.18 3.19±1.04 0.440

"What are the most important factors for you when deciding to participate in a clinical trial?". Each factor was rated on a five-point scale, where 1 – “not important”, 2 –“Slightly important”, 3 – “Moderately important”, 4 -" very important" and 5 –“extremely important”

Questions regarding IC

«How well and clear did researchers answer your questions?»

Not clear Not clear

enough moderately

clear

very

clear extremely

clear

3.51±0.98

• 64% had questions after acquaintance with IC

• 9% refrained to ask question

• 27% didn’t have any questions

• More than half of the participants asked for help when being acquainted with IC.

• Patients seeking help from a researcher, were significantly older and had been "less experienced" in comparison with the group that read the consent on their own.

• In case of researcher’s assistance the acquaintance with the informed consent was reduced threefold. In addition, after reviewing the IC together with the researcher, respondents showed an increase in interest in a clinical trial.

• IC text was easier in young respondents’ group. The group of respondents who rated the IC as easy appeared to be more interested in the final results of the study.

• Patients acquainting with IC together with researcher show better understanding of the essence and methodology of clinical trials, are more aware of the GCP principles, better informed about participation risks correctly evaluate the probability of getting into the placebo group and are ready to higher organizational and clinical load in comparison with the actual practice.

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Experience of participation in clinical trial

Experience of Participation in Clinical Trials

“How burdensome was it to visit the clinic?"

not

burdensome

somewhat

burdensome moderately

burdensome

very

burdensome extremely

burdensome

1.40±0.74

• 78% had no doubt about continuing clinical trial

• 72% pointed themselves as motivator to continue the trial

• 23% pointed researcher as motivator to continue the trial

Factors that motivated to continue clinical trial

Factor Average score

Permanent monitoring of my condition 3.65±1.04

My relationships with doctors/ researchers 3.56±1.02

Good response to treatment and improvement of physical condition 3.49±1.01

Free examinations and medical care 3.47±1.10

Free medications 3.43±1.19

Permanent monitoring of my condition 3.16±1.03

Unspoken promise, agreement (sense of responsibility) 2.86±1.13

"What are the important factors that motivated you to continue the clinical trial?". Each factor could be rated on a five-point scale, where 1 – “not important”, 2 –“Slightly important”, 3 “Moderately important”, 4 -" very important" and 5 –“extremely important”

Meeting Expectations

«How well your expectations about clinical trial were met?»

expectations

not met

somewhat

met moderately

met

highly

met expectations

fully met

3.34±0.92

• 82% are willing to take part in clinical trials in the future

• 11% doubted re-engagement

• 7% are not ready to participate again

• 89% will recommend to friends and relatives to attend

Communications

Communications

• 51% have never discussed participation in CT

• 19% constantly discussed participation in CT

• 81% stay in touch with the researcher

• 69% from researcher

• 19% call from the hospital

• 12% mass media, acquaintances, other

• The majority of respondents evaluated visiting the clinic for CT comfortable and had no doubt of the need to continue participation in CT.

• The most important motivating factors were constant supervision of the state, personal relationships with researchers, improvement of physical condition, as well as free medical examination and medical care.

• Overall, respondents' expectations of participation were justified. Based on the self experience, the majority of patients are willing to participate in clinical research in the future and will recommend participation to their friends and family.

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• Results of the study showed that expectations, motivation and

experience of participation of patients in clinical studies on the territory of the Russian Federation are comparable with the world's data.

• The findings illustrate a significant role of the physician in virtually all

aspects of patient participation - taking decisions on participation, introduction to the informed consent, the motivation to continue clinical trial. Even after the end of the study the majority of respondents are in touch with the researcher.

• On the one hand, the study revealed specifics of the relationship between researcher and patient in Russia, i.e. close interpersonal contact, creating an atmosphere of trust that allows for comfortable participation conditions, a sense of security and quality health care. On the other hand, there is a likelihood of causing ethical conflict.

Conclusions

• Ivan Anatolyevich Deev, professor of Pediatrics Department,

Division, Siberian State Medical University, DMedSc

• Olga Igorevna Zvonareva, research fellow at Department of Health, Ethics and Society, Maastricht University, Netherlands

• Olga Sergeevna Kobyakova, head of General Medical Practice Division, Siberian State Medical University, DMedSc, Professor

• Evgeny Sergeevich Kulikov, associate professor of General Medical Practice Division, Siberian State Medical University, DMedSc

• Igor Dmitrievich Pimenov, resident at General Medical Practice Division, Siberian State Medical University

The research authors / organization

• Golosova, Tatyana Gennadyevna – head of Pulmonology and Allergology Department, at Novokuznetsk Municipal Children Hospital 4

• Esip, Valeria Vladimirovna – physician of 1st advisory department at Saint-Petersburg State Budget Healthcare Institution “Consultative-Diagnostic Center # 85

• Zhukova, Irina Alexandrovna - associate professor of Neurology and Neurosurgery Division of Siberian State Medical University, PhD

• Zhukova, Natalia Grigoryevna – professor of Neurology and Neurosurgery Division of Siberian State Medical University, DmedSc

• Kirillova, Natalia Alexandrovna – teaching assistant of General Medical Practice Division of Siberian State Medical University, PhD

• Nikitina, Lidia Yuryevna – head of Therapy Division, department of postgraduate education, PhD, associate professor at Khanty-Mansiysk State Medical Academy

Researchers

• Starovoytova, Elena Alexandrovna – associate professor of General Medical Practice Division of Siberian State Medical University, PhD

• Schastnyy, Evgeny Dmitrievich – Head of Affective States Department at Mental Health RI in Tomsk, DmedSc

• Fedorova, Olga Sergeevna – professor of Faculty Pediatrics Division of Siberian State Medical University, DMedSc

• Khurkhurova, Natalia Vyacheslavovna - pulmonologist at Pulmonology Department, Deputy Chief Doctor of Clinical and Expert Work at State budgetary institution of healthcare of Stavropol region "City hospital #2" of Pyatigorsk

Researchers

Invitation to participate

We invite to participate all interested researchers, contract research organizations, manufacturers of medicinal products, universities in the second part of the study Face2Face-2 What’s new:

• open questions • questionnaire for researchers • questionnaire for monitor / sponsor • And much more Research launch is expected in early 2017 Registration: https://goo.gl/forms/FJF15Ryk2o7fmDA43

Contact information: Evgeniy Sergeevich Kulikov +7 906 950 2882 (Telegram, WhatsApp, Viber) skype: evgenyskulikov evgeny.s.kulikov@gmail.com

Publications

• Zvonareva O.I., Kulikov E.S., Deev I.A., Kobyakova O.S., Fedorova O.S., Kirillova N.A., Starovoytova E.A., Zhukova N.G., Zhukova I.A., Esip V.V., Schastnyy E.D., Khurkhurova N.V., Nikitina L.Y., Golosova T.S., Pimenov I.D., Netaeva M.A., Fedosenko S.V. Role of Informed Consent in a Decision-making on Participation in The Clinical Trial: Multicenter study in Russia “Face to Face”. Bulletin of Siberian Medicine. 2016;15(4):40-51. DOI:10.20538/1682-0363-2016-4-40-51 http://bulletin.tomsk.ru/jour/article/view/663/595

• Kulikov E.S., Deev I.A., Kobyakova O.S., Zvonareva O.I., Fedorova O.S., Kirillova N.A., Starovoytova E.A., Zhukova N.G., Zhukova I.A., Esip V.V., Schastnyy E.D., Khurkhurova N.V., Nikitina L.Y., Golosova T.S., Pimenov I.D., Netaeva M.A., Fedosenko S.V. Clinical Trials in Russia Through Patients’ Eyes: Motivation, Expectations, and Perceptions . Clinical Medicine (Klinicheskaya Meditsina). 2017

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