Department of Health Science and Technology
Medicine with Industrial Specialisation
Fredrik Bajers Vej 7D2
9220 Aalborg
Denmark
Title: Optimizing the recruitment for clinical trials at Center for Clinical and Basic Research
Phone 99 40 99 40
Project period: 2 of April 2011 – 31 of May 2012
nd
th
Fax 98 15 40 08
Project group: 609
Synopsis:
Members:
Malene Cording Christensen
Mette Pedersen
Cecilie Weiersøe Skovholm
Recruitment is a paramount aspect of
clinical trials but it is also important that
the right participants are recruited. If the
participants do not represent the general
population within the specific condition,
the validity of the trial decreases.
The aim of this project was to clarify the
characteristics of the participants at CCBRAalborg, how they were recruited, and
their motivation for attending a clinical
trial.
In order to obtain this knowledge a
questionnaire survey was conducted.
The results of the survey indicated that
participants were mostly motivated by
personal benefits and that the distribution
of gender and educational level were
uneven among the respondents. Contrary
the age distribution of the respondents in
general correlated with the distribution
within the specific diseases. Though, due
to a too small sample size it was
impossible
to
conclude
anything
significant.
Supervisor: Parisa Gazerani
Print run: 6
Pages: 27
Appendices: 3
Finished on the 31th of May 2012
The contents of this report is freely accessible, but releases (with listing of the source) may
only be done in agreement with the authors
Preface
This project is created by group 609, on the sixth semester of the education “Medicine with
Industrial Specialisation” at the university of Aalborg.
The project is written in the period; 2nd of April to 31th of May 2012.
The target group for this project is students from Medicine with Industrial Specialisation,
students on related educations, and Center for Clinical and Basic Research, Aalborg division
(CCBR-Aalborg).
This project is created with guidance from Parisa Gazerani, lector at Aalborg University, and
Rasmus Hogreffe Sørensen, MMedSci, project manager at CCBR-Aalborg, which we would
like to thank for their supervision. Furthermore, we would like to give our thanks to the
receptionists at CCBR-Aalborg for handing out our questionnaire.
2
Table of Contents
Preface ................................................................................................................................... 2
Introduction ........................................................................................................................ 4
Clinical trials ................................................................................................................................. 4
Phase I......................................................................................................................................................... 4
Phase II ....................................................................................................................................................... 5
Phase III ..................................................................................................................................................... 5
Phase IV...................................................................................................................................................... 5
The importance of clinical trials............................................................................................ 6
Recruitment of participants............................................................................................................... 6
Center for Clinical and Basic Research................................................................................ 7
Problem statement............................................................................................................ 8
Questionnaire ..................................................................................................................... 9
Method ............................................................................................................................................ 9
Assessment of the questions ........................................................................................................... 10
Descriptive statistic.................................................................................................................. 12
Predictive analysis ................................................................................................................... 18
Cross-tabulation ........................................................................................................................ 20
Level of education versus motivation factor ............................................................................ 20
Level of education versus recruitment strategy ..................................................................... 20
Gender versus motivation factor ................................................................................................... 20
Discussion ..........................................................................................................................21
Conclusion ..........................................................................................................................24
Putting into perspective ................................................................................................25
References ..........................................................................................................................26
3
Introduction
Clinical trials
A clinical trial is a prospective study used to investigate the effect and safety of a possible
new medical treatment. When investigators presents a new idea of a possible new medical
intervention, it will take a lot of time and effort before it can be employed in routine practice,
and only a small percentage will ever be tested in humans. Examples of ideas for a new
intervention can be a new pharmaceutical treatment, a device, or a procedure, which aims to
change aspects of the current standard treatment. (1,2)
Before an intervention can be tested, a project protocol has to be formulated. The protocol
must give a comprehensive description of: reason, background, design, organisation, and
personnel of the trial. In Denmark the protocol has to be approved by several regulatory
authorities: the National Health Service, who has the overall responsibility, and the Danish
Medicines Agency, who assesses the quality and safety. Furthermore, The National
Committee on Health Research Ethics has to be notified to secure the ethical aspects. In this
project, when an intervention is further mentioned it will refer to the idea of a possible new
pharmaceutical treatment. New pharmaceutical treatments have to be approved by the
European Medicine Agency for distribution in Europe and the National Health Service for
distribution in Denmark. (1-5)
Before a new drug can be considered a new treatment option, thorough testing and processing
precedes. First, a group of investigators form a hypothesis, which will be tested in the
laboratory. If the laboratory results suggest a positive outcome, further testing will be
initiated in animals to secure the safety of the drug. After the drug has proven to be safe in
animals, a clinical trial can begin. (1)
There are different ways of funding a clinical trial depending on the applicants. A
pharmaceutical company usually has internal funding, whereas institutions such as hospitals
and universities are obliged to seek external funding. Charities or private benefactors may
provide the financial aspect of a trial, all seeking value-for-money. Therefore, smaller trials
with little impact on the overall public health are assigned a lower priority than larger trials
that aims at more widespread diseases. As a consequence, the chance of getting a grant is
bigger when the results of the trials will lead to a change in the routine practice or give new
important information about a specific and widespread disease. (6)
Clinical trials are divided into four phases, each with a specific purpose. (2)
Phase I
Phase I aims to determine a dose with an acceptable level of adverse effects, called the
maximum tolerated dose. The trial is conducted with a small number of healthy volunteers,
often less than 30 is needed, who are divided into small groups. The first group is given a
small dose, and if tolerable, a higher dose is given to the next group. Escalation continues
until an unacceptable level of adverse effects are observed, thus the maximum tolerated dose
is identified. (7)
Variables like pharmacokinetics and pharmacodynamics are also examined, often in form of
bioavailability and drug distribution in different body compartments. (2)
Data from all observations will in the end determine whether the drug is safe enough for
further investigation. (8)
4
Phase II
Phase II trials determine a preliminary effect of the acceptable treatment dose, found in phase
I. The number of participants varies between 30-70, depending on the design of the trial. If
the intervention has an improving effect on the disease status of the patients, is easier to
administrate, or have a smaller amount of adverse effects, it is considered a better treatment
than the standard treatment. Then the intervention will be further investigated in a phase III
trial. (9)
Phase III
Phase III trials are conducted as randomised controlled trials, where the participants are
allocated randomly into an intervention group and a control group. The intervention group
receive the new drug, whereas the control group receives either the current standard treatment
or a placebo. These trials are large, and hundreds or thousands of participants are needed, and
it takes several years before the final results are obtained. (10)
In the end the results of phase III trials must give an answer to whether the new treatment has
a better effect, the same effect but safer, or is less effective than the current standard
treatment. If the new treatment is more effective or safer, an application for the regulatory
authorities is formed in preparation for marketing the new product. (1,10)
Phase IV
The purpose of phase IV trials is to continue the monitoring of the efficacy and safety of the
new treatment after it is incorporated in routine practice. These trials are large and hundreds
or thousands of participants are involved. (2,7)
Every phase in a clinical trial has specific inclusion and exclusion criteria that the participants
have to fulfil, and these determine the study population. It is essential that the study
population is representative, so the results can be generalised to a larger population. If the
investigators choose many specific criteria, the study population will be more homogenous
and the participants will most likely respond to the treatment in the same way. The advantage
of a study population with little variability is that the effect of the treatment will be easier to
observe, but it can be difficult to generalize the effect to a larger and more variable
population. On the other hand, if there are few criteria, the treatment will be easier to
generalize, but presumably the effect of the treatment will vary more. (7,11)
When the study population is identified, but before the trial is executed, a power calculation
is made to estimate the needed sample size. If the sample size is too small, it can be difficult
to observe differences in the comparison of the treatments and furthermore can give
insignificant and misleading results. On the other hand, a too large sample size will give an
unnecessary spend of time, work and money. In order to conduct a power calculation, the
investigators have to state a null-hypothesis. When testing a null-hypothesis, the possibility
of either rejecting a true null-hypothesis or accepting a false null-hypothesis is present. These
types of errors are called type I and II error respectively. In most trials the significance level
(α) is 0,05, meaning that there is only a 5% risk of rejecting a true null-hypothesis – making a
type I error. The probability for accepting a false null-hypothesis – making a type II error – is
equal to 1- β, also known as the sensitivity. Most investigators want the sensitivity of their
trial to be no less than 80%, thereby making the probability of a type II error happening 20%
(β). (12-14)
5
The importance of clinical trials
Only in few cases, the characteristics of an illness or a disorder are fully understood.
Therefore, it is necessary to continuously investigate illnesses and new interventions, which
will give a better knowledge about how to provide the best treatment for the patients. Clinical
trials are the best way to obtain this knowledge. In a clinical trial an intervention is tested and
later the effect and value is compared to the current standard treatment or placebo. The
comparison provides information about whether the new treatment is more effective and safe
than the standard treatment, which insures that patients always receive the best treatment.
This reduces the morbidity and mortality of the patients and in the end gives them an
improvement in quality of life. (2)
An essential part of a successful completion of a clinical trial is the ability to recruit the
necessary number of participants and to ensure that they remain enrolled in order to
guarantee the validity of the trial and to minimise the costs. Furthermore, the sample
population has to be a representative section of the target population. (12,15)
Recruitment of participants
Recruitment is a process that takes place before the initiation of a clinical trial. It is based on
a dialogue between the investigator and the participant that ideally ends up with the
participant signing the consent form. It is important that participants are provided with
adequate information, which make them aware of the potential benefits and risks associated
with the trial. Equally important is that they gain an interest in the specific trial because this
enhances the retention rate. Participant’s motivation for attending clinical trials varies,
though the foremost reason for participating is potential personal health benefits. Other
reported reasons are physician’s influence, potential benefit to others, desire to learn more
about their condition, and encouragement by friends and family. (14,16)
The various phases of clinical trials need different numbers of participants. Phase I and II
trials require less than 70 participants whereas phase III and IV trials need an extensive
number, hundreds or thousands. Because of the significant impact clinical trials have on
patients and society, the recruitment and continues enrolment of participants is crucial.
(2,3,15)
It can be difficult to recruit participants for every phase but because of the extended number
needed for phase III this is often the most difficult. A randomised controlled trial is the study
design of phase III trials, and the recruitment for this type of trial can be an extensive
problem. This is due to various concerns of the participants, which according to the ECRI
survey mentioned in chapter 10 in “Fundamentals of Clinical Trials” can be: the time
consumption, the use of placebo, concern for experimentations, the possibility of lack of
health benefit, and general inconvenience. If the recruitment for a clinical trial fails leading to
a rejection of the intervention, it is costly for the providing company, which makes the
recruitment paramount. (15,16)
The extend of the recruitment problem is not fully clarified, but a review made by Treweek S
et. al. estimates that less than 50% of the randomised controlled trials are able to recruit the
target number of participants without delaying the start of the trial. (15,17)
The insufficient recruitment of participants leads to underpowered results with lack of
statistically significance. Insignificant results are not tantamount to a non-effective
intervention and therefore a possible improvement of the standard treatment is maybe
overlooked. When a trial is underpowered or extended, it influences both the participants and
the investigators. The participants are exposed to a potential harmful intervention without this
leading to any conclusive results, which is considered an ethical problem. Extension of a
clinical trial results in an increased cost for the providing company, and other investigators
6
may complete a similar trial with conclusive results and furthermore patent the treatment.
(15,16)
Several studies have tried to identify strategies to improve the recruitment of participants for
randomised controlled trials. The following strategies have indicated an improvement.
Open randomised controlled trial versus blinded randomised controlled trial: the use of open
randomised controlled design, where the participants know which intervention they receive,
have a positive impact on the recruitment. (15)
Placebo versus other comparator: if the participants know that they possibly receive a
placebo, they are more likely to decline, in comparison to trials using new intervention versus
standard treatment. (15)
Modification to the consent form or process: The use of an opt-out method, instead of opt-in,
leads to improvement of the recruitment. (15)
Modification to the approach made to potential participants: it shows that by using a short
information video and written information instead of only written information improves
recruitment. (15)
Some of these strategies can be difficult to implement in a trial without compromising the
validity of the trial. Therefore alternative strategies have to be found. To do so we believe it
is necessary to clarify people’s motivation for participating in clinical trials, which we
attempt to do in corporation with Center for Clinical and Basic Research, Aalborg division
(CCBR-Aalborg). (12)
Center for Clinical and Basic Research
CCBR is an international patient recruitment organization that engages in recruiting
participants for clinical trials in 11 countries around the world. The twenty clinical research
centres are located in Europe, Asia, and South America, which give a big potential for
recruitment of numerous patients within different therapeutic areas. (18)
CCBR-Aalborg has existed for the last 17 years as an independent clinical research centre
with the capability to conduct phase I-IV clinical trials. Many years of operation has created a
large patient database, called the CCBR-database, which is used to recruit both healthy
volunteers and patients with a specific condition for clinical trials. CCBR-Aalborg also uses
other recruitment methods, such as the Danish CPR-register, where they buy addresses of
potential participants who directly receive letters regarding future campaigns. In addition,
they use spreads in newspapers and advertisement at Facebook along with radio spots, which
is a new initiative. (18)
CCBR-Aalborg is aware of the importance of patient retention when they conduct a clinical
trial. To obtain a high retention rate CCBR-Aalborg attempt to give the participants an
efficient and good experience when they visit the research centre. Furthermore, CCBRAalborg sends reminding letters, offer breakfast and lunch, and provides a problem free
administration among others for their participants. (18)
CCBR-Aalborg currently focuses on the following therapeutic areas: osteoporosis,
osteoarthritis in knees, and diabetes, which all are age-related chronic disorders. Additionally
CCBR-Aalborg also represents dyslipidaemia, which covers several conditions such as verylow-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density
lipoproteins (HDL). (18-21)
According to CCBR-Aalborg it is generally not difficult to recruit participants for clinical
trials, but because of the variation in number of participants in the four phases, the level of
difficulty increases proportionally with the phases. The recruitment also depends on the
therapeutic area, which means that participants for clinical trials regarding a widespread
disease are easier to recruit for CCBR-Aalborg. Finally, the study design can influence the
7
recruitment, which often is easy if the participants only have to attend once contrary to trials
where participants have to attend for a longer period of time. (22)
CCBR-Aalborg would like this project to clarify why people participate in their clinical trials
and where they learn about the trial they are attending or consider attending. This gives
CCBR-Aalborg an idea of where to centre their advertisement in order to increase their return
of investment. Furthermore, they will like to know the distribution of educational level
among their participants in order to secure a representative study population. Finally, they
have an interest in knowing if participants are easier to recruit, if they previously have
attended a clinical trial at CCBR-Aalborg. (22)
Furthermore, we choose to clarify the participants’ satisfaction with CCBR-Aalborg in order
to evaluate the retention rate.
Problem statement
What motivates people to participate in clinical trials and what is the most effective
recruitment strategy at CCBR-Aalborg?
For several reasons it is important to know what motivate participants to attend clinical trials
and to know where they get information about the trials. When these factors are known, the
content of the advertisement can be directed at people’s motivation and can be published at
the most profitable sites. Even though it is paramount to be able to recruit a sufficient amount
of participants, it is also important that the participants represent the population within the
specific disease. Many factors determine whether a study sample is representative or not, i.a.
age, gender, and level of education.
On the basis of other studies, the following hypothesis is framed, which this project will try
to answer by means of the questionnaire survey.
-
People only participate in clinical trials, if they gain personal benefits. (16)
In clinical trials the gender distribution is uneven. (14,23)
In clinical trials the level of education is distributed unevenly. (14,24)
In clinical trials age is distributed unevenly. (14)
8
Questionnaire
Method
The objectives of this questionnaire survey are to clarify the characteristics of the
participants, their motivation for participating, and the most effective recruitment method.
Furthermore, the questionnaire survey assesses if the participants at CCBR-Aalborg are a
representative section of the general population within the specific diseases.
Questionnaires are a self-reporting method for collecting data and are, compared to
interviews, a cheaper and more effective way to administrate simple questions. We choose to
form a questionnaire because of the use of simple questions and a limited time perspective.
(14)
The questionnaire is conducted with a positivistic approach, which focuses on objective
information of the respondent. The information includes the respondent’s action, experience,
and background. Questions about the respondent’s attitude, which differs from the
positivistic paradigm, are also included. (25,26)
The variables of our questionnaire are both nominal categorical, ordinal categorical, and
continuous metric. Nominal categorical variables are characterised by having no units of
measurement and cannot be organised in a meaningful way. Ordinal categorical variables are
much like nominal variables, but data can be ordered in a meaningful way. Continuous metric
variables can be measured and do have units of measurement. A bar chart is made to provide
an overview and to depict the frequency distribution, which is commonly used when only one
variable is described. To assess a possible correlation between two variables within the same
study sample, a cross-tabulation is used. By using the cross-tabulation method it is possible to
investigate specific tendencies in a sub-group of a study sample. When cross-tabulating
selected data a chi-squared test is used. This test is used for categorical data and tests if the
two compared variables are independent and if their proportions are equal. A null-hypothesis
states that the two variables are not correlated. When using a chi-squared test the p-value has
to be less than 0,05 to accept the null-hypothesis. (25-28)
One continuous metric variable is present, year of birth, where the mean and standard
deviation will be calculated. (29,30)
The respondents are chosen by a group-selection method, meaning that those participants
who are present at CCBR-Aalborg from the 1st of May to the 3th of May are asked to
participate in the questionnaire survey. The receptionists at CCBR-Aalborg handed out the
questionnaires. (25)
The size of the sample depends on the number of participants present in the three days the
questionnaire is handed out. Statistical uncertainty depends on the sample size; the
uncertainty increases, when the sample size decreases. In contrast, the representativity
depends on the participant selection method rather than the sample size. (25)
The questions are formulated as closed questions because open questions are very time
consuming to analyse. The reliability of closed questions is relatively high, but the validity is
relatively low, because only the researchers response categories are analysed. To avoid that
the participants feel obliged to mark one of the prearranged response categories, they have
the opportunity to mark “other” and thereby state that the prearranged response categories do
not cover their opinion. This increases the validity of the questionnaire survey, because the
participants can choose not to use the prearranged response categories. (25)
We choose to formulate the questionnaire in the participants native language, Danish, to
avoid any linguistic misunderstandings. (25)
9
Assessment of the questions
In the following we will assess every question in the questionnaire, and thereby clarify the
reason for asking them and their purpose in our analysis.
Question 1:
1. What gender are you?
Man
Woman
Gender is a nominal categorical variable regarding the respondent’s background, which is
always an important factor in a questionnaire survey, where actions and attitudes are being
analysed. Men and women often behave differently, which can have an importance regarding
e.g. where the participants learn about the trial and if more women than men participate or
vice versa. Maxine X. Patel et. al. reports that the males are poorly represented in psychiatric
trials, whereas Patrick Y. Lee et. al. reports that females are underrepresented in clinical trials
concerning cardiovascular diseases. The gender distribution does not have to be equal, but
have to represent the gender distribution within the specific disease. (14,23,25)
This question helps to clarify whether or not the gender distribution at CCBR-Aalborg is
representative according to the four diseases being investigated; osteoporosis, osteoarthritis,
diabetes, and dyslipidaemia.
Question 2:
2. In what year were you born?
Year of birth (4 digits):
__ __ __ __
Age is a continuous discrete metric variable, also regarding the respondent’s background. It
is an essential factor because older people tend to behave in a different way compared to
younger people. (14,25)
The respondent has to state their year of birth rather than age because experience from other
surveys show that if you ask respondents about their age, you often get a number that is either
rounded up or down. Some people may have forgotten their age and therefore you get a more
precise answer when asking about year of birth. (25)
CCBR-Aalborg mainly investigates age-related diseases and therefore the age of the
participants has to correspond to these, which this question will help determine.
Question 3, 4 and 5:
3. Have you previously attended a clinical trial at CCBR?
Yes
No
4. If yes, where did you learn about the trial the first time you attended the
clinical trial?
Letter from CCBR
Newspaper spread
Family and friends
Facebook
Other
10
5. Where did you learn about the trial that you are attending now?
Letter from CCBR
Newspaper spread
Family and friends
Facebook
Other
The three above mentioned questions are background and nominal categorical variables,
which clarify if the respondent previously attended a clinical trial at CCBR-Aalborg and
where he/she learned about the first trial and the current trial. (25)
The prearranged response categories are based on CCBR-Aalborg’s current recruitment
strategies. (18)
We believe it is favourable to know which current recruitment method is the most effective,
and if it varies from the first time the participant were recruited.
Question 6:
6. What is your motivation for participating in a clinical trial at CCBR?
Potential health benefit
Potential benefits to others
Physician influence
To learn more about my condition
Encouragement by family and friends
Good experience with participation in previous studies
This is a nominal categorical variable and a question regarding the attitude of the participant,
which explains the motivation for attending a clinical trial at CCBR-Aalborg. The
prearranged response categories are based on a review from 2001 summarised in chapter 10
in “Fundamentals of Clinical Trials”. (16)
The reason for asking this questions is to find out what motivates the respondents to attend a
clinical trial, in order to optimise the recruitment e.g. through advertisement.
Question 7:
7. What is your highest level of completed education?
Public school
Upper secondary education
Vocational education
Short higher education (2 years)
Medium higher education (3-4 years)
Long higher education (5 years or more)
This question is a background and ordinal categorical variable. The review by Maxine X.
Patel et. al. states that people with a lower educational level tend to participate less in
psychiatric trials than people with a higher level of education. The question is asked to
investigate whether or not there is the same tendency among the participants at CCBRAalborg and if the participants represent the general population. (14,25,29)
11
Question 8 and 9:
8. If possible, would you consider participating in a clinical trial at CCBR again?
Yes
No
Maybe
Not relevant for me
9. How satisfied are you with participating in a clinical trial at CCBR?
Very satisfied
Satisfied
Unsatisfied
Very unsatisfied
Do not know
Question eight is a nominal categorical variable and question nine is an ordinal categorical
variable. These are questions about the participant’s attitude towards CCBR-Aalborg. (25)
The answers will indicate the respondents’ level of satisfaction, which will be used as an
indicator for the retention rate and to clarify if any improvements regarding the quality of the
respondents experience are necessary.
The respondents’ answers to the questionnaire are enclosed as a CD.
Descriptive statistic
During the three days 99 participants at CCBR-Aalborg answered the questionnaire. Most of
the participants represented these days were generals, who are not yet attending a clinical
trial, but who are potential participants and therefor screened for a specific trial. The
remaining respondents are divided between following diseases: diabetes, osteoporosis,
osteoarthritis, and dyslipidaemia. We do not know the exact number of respondents in each
disease and therefore we are obliged to lump them all together. This makes us unable to
compare one disease with specific data and thereby also unable to clarify a possible tendency
within a specific disease.
Because only 99 participants answered the questionnaire the frequency will be stated in
counts oppose to percentage. (25)
Question I:
As seen in chart I the gender distribution of the respondents proved that 93 of the respondents
were female and only six were male. Thus women were greatly overrepresented in this
questionnaire survey.
12
Chart I:
Gender distribution
100
90
80
70
60
50
40
30
20
10
0
93
6
Male
Female
Chart I depicts the gender distribution of the respondents in the questionnaire survey, where 91 of the
participants were women and 6 were men. At the X-axis gender is presented and at the Y-axis the
count is presented.
Question II:
As seen in chart II the age of the respondents ranged from 60 to 83 years and the average age
was 68 years. The standard deviation was calculated to 3.342, which measure the spread of
age among the respondents, according to the mean. The smaller the standard deviation is, the
narrower is the range of the values. (31)
Chart II:
Year of birth
45
39
40
35
30
25
19
20
15
1
2
2
3
1935
1936
1937
1938
1939
1940
5
4
3
1
1
1
1
2
1952
2
1951
2
1949
1
1929
5
1948
10
10
1947
1946
1945
1944
1943
1942
1941
0
Table I:
Year of birth
Statistics
Year
Mean
1943.8
Standard deviation
3.342
Range
23
Chart II shows the distribution of year of birth among the respondents, which range from 1929 to
1952. The age of the respondents range from 60 to 83, making the average age 68 years. Table I
shows the mean and the standard deviation, which is 1943,8 and 3.342 respectively. At the X-axis
years of birth is presented and at the Y-axis the count is presented.
13
Question III:
As seen in chart III 22 of the 99 respondents had previously attended a clinical trial at CCBRAalborg, which means that 77 of the respondents were newly recruited.
Chart III:
Have you previously attended a clinical trial at CCBR?
90
77
80
70
60
50
40
30
22
20
10
0
Yes
No
Chart III illustrates how many of the respondents who previously have attended a trial at CCBR,
which showed to be 22 out of the 99 respondents. At the X-axis the prearranged response categories
are presented and at the Y-axis the count is presented.
Question IV:
Out of the 22 respondents who previously attended a clinical trial at CCBR-Aalborg, ten
respondents got information about the specific trial via letters from CCBR-Aalborg, nine read
about it in a newspaper spread, one learned about it from family and friends, and two got
information else where. This is depicted in chart IV. No one got the information directly from
Facebook.
Chart IX:
If yes, where did you learn about the trial the first time you
attended the clinical trial?
12
10
10
9
8
6
4
2
2
1
0
Letter from CCBR
Family and friends
Newspaper spread
Other
Chart IV illustrates where the 22 respondents learned about the trial they previous attended. Ten
respondents got information from letters from CCBR-Aalborg, nine from newspaper spreads, two from
else where, one from family and friends, and none from Facebook. At the X-axis the prearranged
response categories are presented and at the Y-axis the count is presented.
14
Question V:
As seen in chart V the majority of the respondents learned about the current trial via letters
from CCBR-Aalborg. The remaining respondents learned about it from family and friends,
newspaper spreads, or other sources. Only two chose not to answer this question. Again, no
one learned about it directly from Facebook.
Chart V:
Where did you learn about the trial you are attending now?
90
81
80
70
60
50
40
30
20
10
0
2
Not answered Letter from CCBR
5
4
7
Newspaper
spread
Family and
friends
Other
Chart V shows the distribution of the effect of the current recruitment strategies used by CCBRAalborg. 81 of the respondents got information from letters from CCBR-Aalborg, seven got
information else where, five from newspaper spreads, four from family and friends, two did not
answer, and none from Facebook. At the X-axis the prearranged response categories are presented
and at the Y-axis the count is presented
Question VI:
The three most frequently marked categories were “Potential health benefits”, “To learn more
about my condition”, and “Potential benefits to others”, accounting for 71 of the answers.
The two first mentioned motivation factors are characterised by a personal gain in contrast to
the latter one. Surprisingly, nine respondents chose not to answer this question. The
remaining responses were shared among “Encouragement by family and friends”, “Physician
influence”, and “Good experience with participation in previous studies” respectively. This is
showed in chart VI.
15
Chart VI:
What is your motivation for participating in a clinical trial at
CCBR?
30
27
25
23
21
20
15
10
11
9
5
3
5
0
Not
answered
Health
benefit
Benefits to
others
Physician
influence
Learn about Family and
Good
condition
friends
experience
Chart VI depicts what motivate the respondents to attend a clinical trial, within the prearranged
response categories. 27 were motivated by the potential personal health benefits, 23 wanted learn
more about their condition, 21 were motivated by the potential benefit to others, 11 were encouraged
by family and friends, nine did not answer, five were motivated by the influence of their physician, and
three were motivated by good experience with participation in previous studies. At the X-axis the
prearranged response categories are presented and at the Y-axis the count is presented.
Question VII:
As seen in chart VII, 69 of the respondents had completed no further education than public
school, upper secondary education, or a vocational education. 30 of the participants have
completed a short higher education, a medium higher education, or a long higher education.
Chart VII:
What is your highest level of completed education?
40
36
32
35
30
22
25
20
15
10
6
5
2
1
0
Public school
Upper
secondary
education
Vocational
education
Short higher Medium higher Long higher
education (2 education (3-4 education (5
years)
years)
years or more)
Chart VII illustrates the distribution of educational level among the respondents. 36 had no further
education than public school, 32 had a vocational education, 22 had a medium high education, six had
a short higher education, two had a long higher education, and one had a secondary education. At the
X-axis the prearranged response categories are presented and at the Y-axis the count is presented.
16
Question IIX:
This question reflects the respondents satisfaction and 91 of the respondents would attend or
considered attending a clinical trial at CCBR-Aalborg again as seen in chart IIX. Only three
declined to participate again.
Chart VIII:
If possible, would you consider participating in a clinical trial
at CCBR again?
60
51
50
40
40
30
20
10
3
3
2
0
Not answered
Yes
No
Maybe
Not relevant for
me
Chart IIV depict whether or not the respondents will attend a clinical trial at CCBR again. 51 will like
to participate again, 40 will consider, three declined, three did not answer, and the question was not
relevant for two respondents. At the X-axis the prearranged response categories are presented and at
the Y-axis the count is presented.
Question IX:
As seen in chart IX, 62 of the respondents at CCBR-Aalborg were satisfied with attending the
clinical trial. The remaining did not know or had not answered.
Chart IX:
How satisfied are you with participating in a clinical trial at
CCBR?
50
45
40
35
30
25
20
15
10
5
0
43
26
19
11
Not answered
Very satisfied
Satisfied
Do not know
Chart IV depicts the level of satisfaction among the respondents. 43 respondents were very satisfied,
26 did not know, 19 were satisfied, and 11 did not answer. At the X-axis the prearranged response
categories are presented and at the Y-axis the count is presented.
17
Predictive analysis
Introductory the results are analysed separately and afterwards selected data are crosstabulated to detect any possible correlations.
Gender:
The results showed that the gender distribution at CCBR-Aalborg, the three selected days,
were very uneven, where the majority of the participants were women. The gender
distribution within the different conditions that CCBR-Aalborg focus on varies but in general
women are overrepresented.
Osteoporosis and osteoarthritis are the only conditions where a distinct difference in gender
distribution exists. Osteoporosis affects one half of every woman and one fifth of every man
over 50 years whereas osteoarthritis affects twice as many women than men. The gender
distribution of diabetes is almost even, whereas the distribution of dyslipidaemia is hard to
clarify because the term “dyslipidaemia” cover several conditions. (19,20,32,33)
Because we did not know which condition each respondent had, it was impossible to clarify
the gender distribution within each condition, which forced us not to distinguish between the
different conditions. Even though osteoporosis and osteoarthritis affect more women than
men, the ratio is not as seen in our survey. Because only two out of four conditions for sure
have a distinct difference in gender distribution, we believe that men in general were
underrepresented these three days. If it proves that male participants are underrepresented
within each condition, which our survey suggests, CCBR-Aalborg should probably focus on
a larger recruitment of male participants. (20)
Age
The range of age among the respondents could appear unrepresentative for the general
population but if you bear in mind the average age distribution within the specific conditions,
we believe that the respondents did represent a representative section of the before mentioned
patient groups. The standard deviation was calculated to be 3.342, which indicate that the
average age is not influenced by any extreme values. (20,34)
Previous and current participation and recruitment strategies
Out of the 99 respondents 22 had previously attended a clinical trial at CCBR-Aalborg and at
that time about half of them learned about the trial through a letter from CCBR-Aalborg,
whereas the other half from newspaper spreads. In the current trials 81 of the respondents
were recruited through letters from CCBR-Aalborg, which makes this the current most
effective recruitment strategy seen in the three days. This could indicate that the effect of
different recruitment strategies can change over time. Though, CCBR-Aalborg continuously
expands their database, which could influence the effect of this strategy.
Furthermore, the contact information of the respondents who received a letter from CCBRAalborg, came either from CCBR-Aalborg’s own database or the Danish CPR-register. It was
impossible to say which register the information was drawn from, which makes it difficult to
detect if there was any difference in the efficacy of the two databases. This could be
beneficial for CCBR-Aalborg to clarify because it is costly to use the Danish CPR-register as
opposed to CCBR-Aalborg’s own database. (22)
The only recruitment strategy that did not have any effect, previously or currently, was the
advertisement at Facebook. This does not necessarily mean that the strategy is ineffective
because it can be a source to secondary recruitment, e.g. through family and friends. So far
CCBR-Aalborg’s advertisement at Facebook has been cost free and therefore we still see this
as a possible effective future recruitment method.
18
Motivation
The clarification of the participant’s motivation for attending clinical trials is crucial for a
successful recruitment. This survey displayed that the participant’s motivation first of all was
personal gain within new treatment methods or detailed information about their own
condition. Besides personal gain, helping others was also a dominant motivation factor. This
knowledge can be used to optimise future recruitment campaigns where the advertisement
can target these motivation factors.
In spite of the fact that CCBR-Aalborg does not have any cooperation with physicians, five
respondents reported that their physician encouraged them to attend a specific trial. This can
be a possible new and yet unexplored recruitment strategy for CCBR-Aalborg.
Eleven respondents were motivated by encouragement by family and friends, which was a
very indefinable factor making it difficult to draw any useful information from this category.
Remarkably, nine respondents chose not to answer the question regarding motivation factors.
If the reason for this was that their motivation factor did not figure in the prearranged
response categories or if they simply did not know is difficult to say. We probably should
have given the respondent the opportunity to mark “other” as we did with some of the other
questions.
Level of education
We chose to divide level of education into two groups, instead of six, due to the small sample
size. The groups were categorised as shorter education (from public school to vocational
education) and longer education (from short to long higher education). 69 of the respondents
had a shorter education, making the remaining 30 of the respondents, with a long education,
underrepresented. Conditions like osteoporosis and osteoarthritis can be related to physical
overload, which mostly is associated with people with physically demanding jobs. It is more
likely that people with a shorter education is exposed to physically demanding work opposed
to people with a higher education. This could partly explain the lack of participants with a
long higher education. A study made by the Danish National Institute of Public Health
reveals that people with a lower educational level in general have more years with diseases
compared to people with a higher educational level. (20,24)
On basis of this study it appears that people with different levels of education may respond
different to a specific treatment and that people with lower educational level are sicker and
therefore may volunteer more. This indicates that educational level probably do have an
impact on whether or not the study sample is representative and that CCBR-Aalborg should
focus on recruiting people with a higher educational level. (24)
Satisfaction survey
91 of the respondents would attend or would consider attending another clinical trial at
CCBR-Aalborg. Furthermore, 62 of the respondents were very satisfied or satisfied with
participating in a current trial, which shows that the over all contentment towards CCBRAalborg is relatively high. The remaining 37 respondents replied “not relevant for me” or did
not reply at all. We believe that the reason for this is that they probably were generals who
were not attending any trial yet. Therefore we believe that the remaining 37 respondents
could be satisfied with CCBR-Aalborg as well, making the 62 respondents an incomplete
picture of the participant’s satisfaction with CCBR-Aalborg.
In general we believe that CCBR-Aalborg’s current strategy regarding retention and the
satisfaction of their participants is adequate.
19
Cross-tabulation
In this section the association between two variables are examined by making a crosstabulation.
Level of education versus motivation factor
Answers to the question regarding level of education showed that the educational level was
not representative due to the fact that 69 of the respondents had a shorter education.
Furthermore, the answers to the question regarding motivation factor showed that 72 of the
respondents chose among three specific response categories.
We want to explore the motivation of the remaining 25 respondents, who all had a higher
level of education, to see if they tended to be motivated by a specific factor. By doing so we
clarify if there is any correlation between the educational level and motivation factor.
This is useful in order to target future campaigns towards the motivation factors of the
participants with a higher educational level, and thereby hopefully recruit more participants
with a high education. This will ultimately make the participants at CCBR-Aalborg more
representative.
The null-hypothesis for this cross-tabulation is: “There is no connection between educational
level and motivation factor”.
The result of the chi square test gives us a p-value at 0,103, indicating no statistically
significant correlation between educational level and motivation factor. Therefore we accept
the null-hypothesis, which makes us unable to suggest the content of a specific advertisement
strategy in order to recruit more participants with a higher level of education aiming at the
participants’ motivation.
The results for this cross-tabulation is shown in appendix I.
Level of education versus recruitment strategy
In order to further optimise future advertisement and make sure that people with a higher
educational level are recruited, it is beneficial to find a possible correlation between
educational level and recruitment strategy.
The null-hypothesis used is as follows: “There is no connection between educational level
and recruitment strategy”.
We got a p-value at 0.671, which indicate that there is no correlation between levels of
education and recruitment strategies. Therefore this hypothesis is also accepted.
We believe that the reason for not getting any significant test results, when using educational
level as a variable, even though we grouped the categories, is due to a too small sample size.
Therefore we choose not to cross-tabulate any other category with educational level.
The results for this cross-tabulation is shown in appendix II.
Gender versus motivation factor
As mentioned above the gender distribution at CCBR-Aalborg is not representative the three
days, for which reason it would be interesting to investigate where the male respondents
learned about the trial they are attending. By clarifying this CCBR-Aalborg can optimize the
specific recruitment method and hopefully be able to recruit more male participants.
The following null-hypothesis is formulated: “There is no connection between gender and
motivation factor”.
As a result of the chi-square test we got a p-value at 0,251, which means that there is no
significant correlation between gender and motivation factor. Therefore we accept the nullhypothesis.
The lack of a significant correlation between gender and motivation factor is probably due to
the too small sample size and a too large difference in the number of men and women. We
20
cannot show a tendency from only six male participants and therefore we do no further crosstabulation of gender with other variables.
The results for this cross-tabulation is shown in appendix III.
Discussion
The results showed an uneven distribution of educational level and gender. Furthermore, the
results showed that most of the respondents in the survey were motivated by personal factors
and were recruited by letters from CCBR-Aalborg. The survey also showed that the level of
satisfaction among the respondents were high. Finally the cross-tabulations showed no
significant results, indicating no correlation between the variables investigated. ma
The method
The questionnaire was constructed with only closed questions, opposed to an interview or a
questionnaire with open questions. Due to the limited time perspective and the use of
statistical analysis, closed questions were the obvious choice. Though, it is possible that more
useful answers would have been obtained by using open questions, especially in the question
regarding motivation factors.
If a pilot study with few participants from CCBR-Aalborg were interviewed about their
motivation factors among others, the answers could have been used as the foundation of the
questionnaire. In this way other response categories may have been constructed on the basis
of the participant’s persuasion instead of other studies. In the end the knowledge obtained
from the interviews and the knowledge obtained from other studies combined could have
been used to construct a much more comprehensive questionnaire, which takes the
participants at CCBR-Aalborg into account. For this project two questionnaires were
constructed, but after handing out the first one, several mistakes and uncertainties were
discovered. Therefore a new questionnaire was constructed.
The interviews would have improved the questionnaire survey and handing out the
questionnaire twice would probably have been avoided.
Before the questionnaire was handed out, no calculations regarding a valid sample size were
made, which lead to a too small sample size and insignificant results. This influential error
was mostly due to ignorance and lack of experience regarding the construction of a
questionnaire. The questionnaire was handed out three successive days, mostly because of
convenience instead of ensuring the representativity of the respondents. By calculating a
minimum sample size this survey may have provided CCBR-Aalborg with useful
information, regarding which recruitment strategy is the most effective and if their
participants are a representative section of the respective patient groups. If the time
perspective was different handing out the questionnaire three days a month over e.g. six
months could have enhanced the representativity of the sample population. This could have
been possible if we from the beginning of the project were aware of the necessity of a power
calculation.
The sample population was based on respondents who already attended a clinical trial. To
improve the recruitment it probably would be more informative to ask people who declined
to participate in clinical trials about their reasons for declining. Furthermore, to make the
study more specific you could base the study on patients within a specific patient group e.g.
osteoporosis. However this would be a very comprehensive and time consuming study.
21
The questionnaire
For several questions the response rate was not 100%. This was possibly due to the fact that
respondents misunderstood the questions, which possibly could have been prevented if we
handed out the questionnaire ourselves. On the other hand, this could have provided a source
of bias, because we could have affected the respondents’ answers. The response rate could
also be influenced if the respondents did not answer due to the questions being too
discriminating or personal. We believe that if the respondents were interviewed this issue
could have been managed by asking the question differently or getting the respondent’s view
on why he/she chose not to answer.
All the obtained results were affected by the fact that the respondents had four different
conditions. This makes us unable to detect any tendencies regarding gender, age, and
motivation etc. If the respondents were asked to state which of the four conditions they had, it
would be possible to find out whether or not the participants at CCBR-Aalborg were
representative according to the specific condition. As mentioned before gender was not
representative compared to the population suffering from these four conditions, but it is
possible that they are: if the distribution within the conditions were known, it would be
possible to calculate the exact gender distribution within the specific condition and thereby
compare this to the actual distribution. In the end this would give a more precise picture of
CCBR-Aalborg´s gender representativity, but keep in mind that a larger sample size is still
needed in order to detect the true distribution.
It is highly probable that the conditions CCBR-Aalborg currently focus on will differ from
the conditions they will focus on in the future. Therefore CCBR-Aalborg continuously has to
target recruitment strategies to the specific conditions in the specific time. Even if this survey
had provided conclusive results they would only be applicable for the current recruitment
strategies.
The analysis:
In order to get a descriptive picture of whether or not the gender distribution was
representative, it is necessary, as mentioned before, to know the gender distribution within
the specific conditions. It is only possible to estimate the gender distribution on the basis of
the survey but it is impossible to make any conclusions. It is possible that one or more
conditions have a representative gender distribution at CCBR-Aalborg, although the
estimation states otherwise.
If, however, the gender distribution within the specific conditions were uneven it would be
beneficial to clarify if there is any correlation between gender and recruitment strategies. This
could enhance the recruitment of a specific gender, which in the end gives CCBR-Aalborg a
more representative patient group.
The same circumstances apply for the age distribution; therefore we cannot say if our sample
is representative for the target population.
Due to the small sample size the three questions regarding recruitment strategies are not valid
enough to conclude the most effective strategy. However, it seems that letters directly from
CCBR-Aalborg to the participants was the most effective. It was not possible to differentiate
between the letters sent from the CCBR-database and the letters sent form the Danish CPRregister and thereby we cannot specify the effect of each register.
On basis of the review summarised in chapter 10 in ”Fundamentals of Clinical Trials” the
response category “Family and friends”, regarding the questions concerning recruitment
strategies and motivation factors, was included. However, one can argue that this category
was unnecessary because the results were indefinable and difficult to implement in future
campaigns.
22
If the sample size had been large enough to make conclusions, it may have been possible to
define how a specific population group was recruited. These results could have been useful in
order to optimise specific recruitment strategies, making them target specific underrepresented sections of the study population.
Faulty, the respondents did not have the opportunity to mark “other” regarding the question
about their motivation. Nine respondents chose not to answer this question, probably because
their motivation factor was not included in the prearranged response categories or because
the question was too personal. If they had the opportunity to mark “other” and furthermore if
it were possible to state different motivation factors, a more comprehensive and precise
picture of the motivation for attending a clinical trial would have been presented. The
motivation factor is specifically important in the survey because it states the participant’s
reason for attending the trial, which could be conveyed into specific campaigns.
As mentioned in the predictive analysis CCBR-Aalborg should focus on recruiting a larger
number of participants with a higher level of education to make their participants more
representative. Based on a study made by the Danish National Institute of Public Health, it is
possible that the distribution of educational level is not equally distributed among the
population with the specific conditions. The study claims that people with a lower
educational level tend to have more years with illnesses and a shorter life than people with a
higher level of education. Therefore, in order to get the most representative study sample, it is
necessary to identify the distribution of educational level within each condition.
The last two questions regarding the respondent’s attitude towards CCBR-Aalborg would
have been more beneficial to construct as open questions, because open questions are more
informative. Furthermore, a question like “what could CCBR-Aalborg do better?” could be
used to improve the participants experience at CCBR-Aalborg, and thereby enhance the
possibility of recruiting the same participants again and increase the retention rate. This
aspect can be beneficial for CCBR-Aalborg according to their costs; it is almost cost free to
recruit previous participants because their contact information already is in the CCBRdatabase.
In this survey these questions could not help to answer the problem statement but it is still
worth further investigation due to its impact on the retention-rate.
Due to invalid results it was impossible to see any significant correlations between the
different variables presented in the questionnaire. The reason for cross-tabulating different
variables was to detect any possible correlations between the stated variables in order to use
specific strategies to target future campaigns towards certain population groups.
Even though the results were inconclusive we believe that the survey could have provided
useful information to CCBR-Aalborg if we had a sufficient sample size.
23
Conclusion
Even though none of the results were significant they were in general in agreement with our
stated hypothesis. Just as the review summarized in “Fundamentals of Clinical Trials” our
results indicates that participants are motivated by personal benefits. In agreement with the
studies made by Maxine X. Patel et. al. and Patrick Y. Lee et. al. the results shows an uneven
distribution of gender and educational level. Maxine X. Patel et. al. also stated that age is
unevenly distributed in psychiatric trials but we found that the age of the respondents in
general correspond within the diseases that CCBR-Aalborg focus on.
Even though the questionnaire survey is in overall agreement with the stated hypothesis, the
too small sample size makes us unable to conclude anything significant. Therefore it is
impossible to suggest any improvement of the current strategies, in order to optimize the
recruitment, without further investigation.
24
Putting into perspective
Here we have collected some of the ideas we have had for further investigation during the
project period.
Use physicians and pharmacies as a recruitment strategy:
In the questionnaire five of the respondents reported that their physician motivated them to
attend a clinical trial at CCBR-Aalborg. This indicates that physicians could be interested in
referring patients to CCBR-Aalborg, which could influence the recruitment rate at CCBRAalborg. CCBR-Aalborg could explore the opportunity for sending monthly newsletters to
physicians, concerning new clinical trials and the specific type of participants they are
looking for. This strategy could also be implemented at the local pharmacies, where an
information sheet about a specific trial could be enclosed to specific medication.
Which database is the most effective?
When CCBR-Aalborg uses the Danish CPR-register is it associated with economical costs
opposed to using their own CCBR-database. It could be beneficial for CCBR-Aalborg to
investigate the efficacy regarding the two databases, in order to potentially decrease their
costs.
Inconvenience
Other studies have reported that inconvenience is one of the reasons for declining
participation in clinical trials. It could be interesting to know what the term ”inconvenience”
covers according to the participants at CCBR-Aalborg. If inconvenience is related to
logistical problems, it could be beneficial to clarify if the participants tend to come from the
city and not from other districts. If this is the case, focus could be to recruit people from
remote areas, which probably could enhance the number of participants. Further studies
should then clarify why people from remote areas do not attend clinical trials and what they
find inconvenient.
Cost-benefit
As before mentioned CCBR-Aalborg uses different advertisement strategies, some more
costly than others. CCBR-Aalborg can use the information about how costly one strategy is
compared with how many participants they recruit, in order to increase their return of
investment.
25
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