Appendix 2: Additional information on the clinical trials and ailments

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Appendices

Appendix 1: List of topics for the in-depth interviews ... 2

Appendix 2: Additional information on the clinical trials and ailments ... 4

Appendix 3 - Patient interviews ... 7

Appendix 4 – Expert Interviews ... 24

Appendix 5 – Questionnaire for participants ... 32

Appendix 6 – Questionnaire for non-participants... 45

Appendix 7 – Development of the questionnaire ... 55

Appendix 8 SPSS Output ... 61

Factor analysis ... 61

Scale reliability ... 67

VIF values and tolerance levels ... 71

Binary logistic regression models – whole sample ... 72

Regression scores for the sobel-test ... 72

Binary logistic regression results – men ... 73

Binary logistic regression results – women... 74

Chi-square tests ... 75

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Appendix 1: List of topics for the in-depth interviews

In-depth interviews with patients

Below, a list of topics for the in-depth interviews with patients can be found. This list functioned as a guideline for the interviews.

- How and when did the patient hear about the clinical trial? How was the conversation with the physician/research nurse?

- Opinion on the quality of the informed consent

- Would the patient also have participated in the clinical trial if a research nurse had asked this?

- Description of the patient-physician relationship

- How long has the patient been treated by the physician?

- Description of the physician’s reputation - Advantages of participating in the clinical trial - Disadvantages of participating in the clinical trial - Degree of perceived risk

- Presence of additional services - Quality of additional services

- Influence of personal sources such as family and/or friends

- Does the patient know by whom the clinical trial is conducted? What do they think of the pharmaceutical industry?

- Use of advertisements as a recruitment tool

- Progress (how often does the patient has to go to the hospital) - Satisfaction rate

- Description of the relationship with the members of the study team - Intention to complete the entire trial? Why (not)?

In-depth interviews with health care professionals

Below, a list of topics for the in-depth interviews with health care professionals can be found.

This list functioned as a guideline for the interviews.

- Experience with the execution of clinical trials (how long, what kind of trials)

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- Does it matter who (i.e., the physician or research nurse) asks the patient for the clinical trial?

- How does this conversation normally go?

- Does the information quality influences a patient’s decision of whether or not to participate in a clinical trial?

- Does it matter if the patient has a long and good relationship with the physician?

- Reputation of the physician

- Use of advertisements as a recruitment tool - How to diminish the amount of perceived risk?

- Perceived value (what is in it for the patient?)

- Are patients aware of the fact that the clinical trial is conducted by a pharmaceutical company? Does this influence the decision of whether or not to participate?

- Influence of personal sources such as family and/or friends

- Presence of additional services (and its influence on both adoption/retention rates) - Customer satisfaction

- Does the relationship the patient has with the members of the study team influence retention rates?

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Appendix 2: Additional information on the clinical trials and ailments

For both the qualitative and quantitative research part, three different groups of patients have been examined. Below more information on these patient groups and the clinical trials in which they participate can be found.

Trial A

Trial A is an international, multicenter, randomized, double-blind, double-dummy, parallel group study that is conducted among men and women who suffer from symptomatic pulmonary embolism. A pulmonary embolism is a sudden blockage in the lung artery.¹ It is usually caused by a blood clot in the leg. This clot breaks free from the vessel wall and subsequently travels through the bloodstream to the lung. Pulmonary embolism is a serious condition. It can cause permanent damage to the affected lung and to other organs in the body.

Symptoms of pulmonary embolism include a rise in temperature, shortness of breath, chest pain, coughing up blood, and possible palpitation of the heart.

Fig. 1: Visual explanation of a pulmonary embolism (source adapted from www.vascularweb.org/

patients/NorthPoint/Pulmonary_Embolism.html)

Pulmonary embolism can be treated with warfarin. Warfarin is an anticoagulant - a substance that stops blood from clotting. The goal of trial A is to determine whether another molecule, biotinylated idraparinux, is as least as effective as a standard warfarin treatment in preventing recurrence of clot in legs or lungs and to assess its safety (bleedings) versus warfarin.² Trial A

1www.nlm.nih.gov/medlineplus/pulmonaryembolism.html

2 Source: internal documents of sanofi-aventis

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has started in 2006 and the estimated study completion date is March 2010. In the Netherlands, 185 people currently participate in this clinical trial.

Trial B

Trial B is a randomized, single blind, parallel assignment, safety/efficacy study that is conducted among women who have been diagnosed with benign cancer in one of their breasts. Benign breast cancer is frequently encountered in female patients, a significant portion of who are premenopausal women.³ Benign tumors should not be confused with cancer and do only grow in one place. They cannot spread or invade other parts of the human body.⁴ However, benign tumors can be dangerous when they press on vital organs, such as the heart, lungs or brain.

Trial B is executed in a mid-sized hospital in Utrecht. The purpose of the study is to determine the efficacy and relapse rate of low dose, short duration treatment with tamoxifen in benign breast cancer disease amenable to hormonal therapy with respect to etiology and estrogen receptor status and to realize its side-effects and cost of therapy.⁵ Trial B1 has started in 2006 and the estimated study completion date is March 2010. In the Netherlands, 450 women in the age of 18 to 75 years currently participate in this clinical trial.

Trial C

Trial C is a factorial, randomized trial among men and women with type 2 diabetes mellitus.

Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or cells stop responding to the insulin that is produced, so that glucose in the blood cannot be absorbed into the cells of the body.⁶ The disease is often characterized by excessive thirst, hunger, fatigue, increased urination, weight loss, and nausea. According to the 2008 figures of the Dutch National Institute for Public Health and Environment, 850.000 people have diabetes mellitus. This number increases with 72.000 per year. There are two types of diabetes mellitus. In type 1 diabetes, the body produces little or no insulin. People with type 1 diabetes need daily injections of insulin. Type 2 diabetes is a milder form of diabetes because of its

3 http://www.clinicaltrials.gov/ct2/show/NCT00999921?term=benign+cancer+in+breast&rank

4 http://www.nlm.nih.gov/medlineplus/benigntumors.html

5 http://www.clinicaltrials.gov/ct2/show/NCT00999921?term=benign+cancer+in+breast&rank

6http://medical-dictionary.thefreedictionary.com/diabetes+mellitus

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slow onset.⁷ It can usually be treated with oral medication or a change in diet. Type 2 diabetes is more common than type 1.

Fig 2: Visual explanation of diabetes mellitus (source adapted from http://patient.co.uk/showdoc/Pilsin1/124.gif)

The goal of trial C is to determine whether a fixed low-dose of perindopril-indapamide combination (normally used for treating adults with mild to moderate high blood pressure) and intensive glucose control with a modified-release gliclazide-based regimen reduces the chance of vascular diseases among high risk individuals with type 2 diabetes.⁸ The study started in 2003 and will end in 2010. In the Netherlands, 800 people participated in this clinical trial. All participants are 45 years or older.

7http://medical-dictionary.thefreedictionary.com/diabetes+mellitus

8 Source: internal documents of Andromed, a Dutch Clinical Research Organization (CRO)

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Appendix 3 - Patient interviews

Participant 1

Gender: Male

Age: 58

Region: Rotterdam

Clinical trial: Trial A

In 2007, participant 1 had some problems with his lungs and was hospitalized. After his stay in the hospital, he was assigned to a lung specialist. After a year, participant 10 had a pulmonary embolism. Shortly after, his lung specialist asked him if he wanted to participate in a clinical trial. The relationship with and reputation of his lung specialist was one of the reasons why participant 1 decided to participate in the clinical trial:

‘My lung specialist is a nice guy. I’ve known him for quite a while and he really cares about his patients. I think he has a good reputation. When he asked me for this trial, I didn’t have to think about it. I’ve always done volunteer work and I think it’s important to help other people in life. I knew there were some risks involved, but I didn’t really care about it. My lung specialist knows what he’s doing and if the trial was really dangerous, he wouldn’t have asked me to participate. Moreover, it was quite advantageous for me to participate. I have to go to the hospital more often, which gives me a feeling of safety. Moreover, I’m helping other people. I know what’s in it for me.’

Participant 1 thinks he is well-informed about the clinical trial. His lung specialist explained the ins and outs of the trial and the written information was clear and understandable.

Participant 1 thinks the information transfer plays an important role in a patient’s decision of whether or not to participate in a clinical trial. He would not have participated in this trial if his physician did not make the effort to explain the trial in detail.

Before participant 1 decided to participate in the clinical trial, he talked about it with his wife:

‘After my lung specialist had asked me for this trial, I discussed it with my wife. Although she didn’t have the feeling my lung specialist involved her in the process, she did support my

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decision. Nowadays she still is very supportive. She joins me when I have to go to the hospital for check-ups. I like the fact that she appreciates what I’m doing, because it keeps me motivated.’

The lung specialist told participant 1 about the trial. However, participant 1 would also have participated if a research nurse had asked him. He does not attach importance to status. When asked if he knows this trial is conducted by the pharmaceutical industry, the answer is yes. He is quite positive about the pharmaceutical industry and thinks it is an indispensable industry.

Participant 1 is participating in this clinical trial since 2008. He is very satisfied with the execution of the trial and he considers his relationship with the members of the study team as close:

‘The members of the study team are always nice to me. They schedule my appointments before 9AM so I don’t have to take a morning off from work. When I come in, I always get a cup of coffee and a free parking card. I knew this up front and it makes participating in the trial much easier. It also gives me the feeling of being appreciated. All in all I’m very satisfied.

There is, however, one point that could be improved. It would be nice to get monthly updates on the progress of the trial. So far, I have no idea what happens with the test results.’

When asked if participant 1 thinks it is a good idea to recruit patients via advertisements in magazines or on the internet, the answer is yes. Participant 1 thinks more and more patients search online for information on their disease:

‘Patients become more and more independent. I’ve the feeling that most patients want to know everything about their disease and new treatment methods. They search on the internet for information. I could imagine that when they see an advertisement for a clinical trial that involves a new treatment method for their disease, they would be interested in participating in this trial.’

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9 Participant 2

Age: 62

Participant 2 suffers from diabetes and lung problems. He was asked for the clinical trial by his lung specialist after he had a pulmonary embolism. At that time, he had known his lung specialist for more than a year. He considers the relationship with his lung specialist as close.

This was one of the reasons why he decided to participate in the clinical trial:

‘I have visited my lung specialist several times. I’ve known him for quite a while. I think he’s a nice, honest guy with a good reputation. He doesn’t talk nonsense and respects me. When he asked me for this trial, I had some doubts, because I was a bit concerned about the risks.

I’ve discussed the risks with my lung specialist. He comforted me and eventually I decided to participate, because I realized the benefits were more important than the potential risks. I do volunteer work and in this way I can help my physician and other people who suffer from this ailment.’

Participant 2 is satisfied with the written information and the information he got from his lung specialist. It was clear and understandable and his lung specialist was able to answer all his questions. Participant 2 thinks his lung specialist handled the conversation in which he told him about the clinical trial very well:

‘He was able to reassure me and took enough time to answer my questions. This indicates he really cares about me. It made my decision to participate much easier.’

Participant 2 considers his lung specialist as a ‘wise man”. He would not have participated if a research nurse had asked him. Participant 2 thinks it is the job of the physician to ask patients for a clinical trial, as physicians know what they talk about.

Before participant 2 decided he wanted to participate in this clinical trial, he talked about it with his best friend:

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‘I’ve known my friend for more than twenty years. We love to ride the motorcycle and we see each other quite often. When I told him about this trial, he was very supportive. I’m glad I talked about it with him, because I don’t know whether I’d have participated if he didn’t support it. Probably not. Nowadays he still is very supportive. He sometimes joins me if I have to go to the hospital for a check-up and is interested in the ins and outs of this trial.’

Participant 2 is very satisfied with the execution of the trial:

‘My lung specialist and the research nurses are very nice to me. We have a special bond. I always get a cup of coffee when I come in and the hospital pays my traveling expenses. I appreciate this, as it is quite expensive for me to get here. I don’t know whether I would have participated if I didn’t get these expenses back, because I rather spend my money on other things.’

Participant 2 does not know this trial is sponsored by the pharmaceutical industry. When asked if he has seen advertisements in the paper in which participants for clinical trials are asked, the answer is yes:

‘I’ve seen some advertisements about clinical trials in the newspaper. I don’t know if I would respond to such an advertisement. Probably. As long as it does not cost me a lot of time.’

Participant 3

Age: 54

In 2008, participant 3 was hospitalized because of a pulmonary embolism. During his stay in the hospital, his lung specialist asked him if he wanted to participate in a clinical trial. He was very enthusiastic:

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‘Although I had just met my physician, I immediately saw him as a trustworthy, nice, and decent guy. He knows what’s good for his patients. That is why I didn’t have to hesitate when he asked me for this clinical trial. Moreover, I’ve always done volunteer work and participating in this clinical trial enables me to help other people. It also gives me a feeling of safety. I have to go to the hospital for check-ups more often. In this way, my lung specialist is better able to keep track of my health.’

Before participant 3 decided that he wanted to participate in the clinical trial, his lung specialist explained the ins and outs of the trial. He thinks the information he received was of high quality:

‘The informed consent was well-organized and clear. I’ve also had a conversation with my lung specialist. I’ve experienced this conversation as very pleasant. He took all the time to explain the content of the trial and gave me enough freedom of choice. I was a bit scared after reading the informed consent, but my physician told me that I didn’t have to worry and that I could quit whenever I wanted to. This reassured me and diminished the amount of perceived risk.’

When asked if participant 3 would also have participated in the clinical trial if a research nurse had asked him, the answer is yes. Participant 3 thinks research nurses are knowledgeable enough to ask patients for clinical trials. When asked if participant 3 thinks it is a good idea to use advertisements to recruit patients, the answer is no. He thinks the physician or research nurse should approach the patient, since this is more personal.

Before participant 3 decided he wanted to join the clinical trial, he discussed it with his wife:

‘My wife was very supportive. Especially when I told her I could contribute to the development of medicines for future generations. She often joins me when I have to go to the hospital for check-ups. This keeps me motivated, since the check-ups are more ‘fun’ when she is around.’

Participant 3 is aware of the fact that the trial is executed by the pharmaceutical industry. He worked as a financial controller for a pharmaceutical company and therefore knows how

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important it is to perform clinical trials. The negative reputation of the pharmaceutical industry did therefore not withdraw him from participating in this trial.

Participant 3 is satisfied with the execution of the clinical trial:

‘The physician and research nurses are very nice. We laugh a lot. I always get a cup of coffee and I sometimes receive little gifts. I appreciate this. I also get a travel allowance. I knew this up front. It makes participating in the trial much easier and it motivated me to sign up for this trial.”

Participant 4

Age: 62

In 2009, participant 4 was hospitalized because of a pulmonary embolism. During his stay in the hospital, his lung specialist asked him if he wanted to participate in a clinical trial. He had to think about it:

‘When my lung specialist asked me for this clinical trial, I wasn’t sure whether I wanted to participate. I have a job and I was afraid that it would cost me a lot of time. On the other hand, I do volunteer work and I think it’s important to help other patients who suffer from the same disease. In addition, my lung specialist was very nice. He has a good reputation and I didn’t want to let him down.’

Eventually, participant 4 decided that he wanted to participate in this trial, but not before he had a conversation with his wife and kids:

‘Before I decided that I wanted to participate in this trial, I talked about it with my wife and kids. I wanted to know what they thought of it. Fortunately, my wife thought it was a good idea. She often joins me when I have to go to the hospital. My kids were less enthusiastic, but they told me it was my decision.’

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Participant 4 is very satisfied with the trial information he received. According to him, the content of the informed consent was clear. There were some difficult sentences in it, but his lung specialist took all the time to explain the ins and outs of the clinical trial. When asked if participant 4 would also have participated in the clinical trial if a research nurse had asked him, the answer is no:

‘I don’t think I would have participated in this trial if a research nurse had asked me.

Research nurses are less knowledgeable than physicians and I don’t think they’re capable of asking these types of questions.’

Participant 4 is aware of the fact that the clinical trial is conducted by a pharmaceutical company. This did not withdraw him from participating in the trial. When asked if participant 4 thinks it is a good idea to use advertisements as a recruitment tool, the answer is yes. He elaborates on this as follows:

‘I know it’s very difficult to recruit patients for clinical trials. That’s why I think advertisements could be a powerful recruitment tool. Not everybody is aware of the possibility to participate in a clinical trial. Advertisements could create awareness and make participating in a clinical trial more popular.’

Participant 4 is very satisfied with the execution of the clinical trial:

‘My lung specialist and research nurses are very nice. They’re interested in my personal life and don’t try to rush things. They respect me and tell me I’m doing a good job. This definitely motivates me to continue with the trial.’

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14 Participant 5

Gender: Female

Age: 48

Region: Utrecht

Clinical trial: Trial B

Participant 5 was diagnosed with benign cancer in 2009. After the diagnosis, she was referred to an internist. During her first meeting with this internist, he asked her if she wanted to participate in a clinical trial. She had to think about it. During the second meeting with her neurologist, she asked for more information about the trial and eventually decided that she wanted to participate. She elaborates on this decision as follows:

‘When my internist asked me for this trial, I wasn’t sure whether I wanted to participate.

Eventually I decided to participate, because I have a lot of faith in my internist. He took a lot of time to inform me and eventually he is the one who knows what’s best for me. I don’t know if I would have participated if a research nurse had asked me. Probably not. I think it’s the task of the physician to ask patients for clinical trials, as only he or she knows what’s best for the patient.’

Participant 5 has always done volunteer work. She thinks it is important to help other people.

By participating in this trial, she can help other women with benign cancer. Moreover, it gives her a feeling of safety that she has to go to the hospital for check-ups more often. This feeling of safety also reduced the amount of risk:

‘I knew there were some risks. I decided not to think about it too much and focused on the benefits of the trial.’

Participant 5 thinks the information from the informed consent was clear and organized. She does, however, have one point of criticism; the informed consent comprised of too much information. Participant 5 knows this trial is conducted by a pharmaceutical company. She is positive about the pharmaceutical industry and associates it with the development of new medicines. She says the so-called negative image of the industry did not withdraw her from participating in the clinical trial.

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Before participant 5 decided to participate in this trial, she asked her husband for advice:

‘I wanted to know what my husband thought of this trial. He was very positive, but eventually it was my decision to participate. It’s my life and I take my own decisions, regardless of what my family or friends tell me. Nowadays we sometimes talk about the trial. My husband supports me and is very proud of me. This motivates me to continue.’

During this trial, participant 5 met another woman who also participates in this trial. She likes to talk with this woman. Since they both suffer from the same disease and participate in the same trial, they can share experiences and feelings. Participant 5 is glad she had the opportunity to meet other people via this trial. She is also very satisfied with the study execution:

‘I enjoy participating in this trial. My internist always takes time for me, he is nice and he often says I’m doing well. The same goes for the research nurses. This keeps me motivated. I get a reimbursement for travel expenses and sometimes they give me a little present. I like these little presents. It gives me the feeling of being appreciated.’

When asked if participant 5 thinks it is a good idea to use advertisements to recruit patients for clinical trials, the answer is no. Participant 5 attaches importance to status and thinks recruiting patients is a physician’s job.

Participant 6

Age: 32

Region: Utrecht

Clinical trial: Trial B

Participant 7 was diagnosed with benign cancer in 2008. After the diagnosis, she was referred to an internist. During her first meeting with this internist, he asked her if she wanted to participate in a clinical trial. She was very enthusiastic:

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‘When my internist asked me for this clinical trial, I immediately wanted to participate. My internist has always been nice to me. He is trustworthy and answered all my questions.

Moreover, he did not push me into this trial. He was very objective. The informed consent was clear and organized as well. I don’t know whether I would have participated if a research nurse had asked me. I don’t think so. After all, they’re not the specialists.’

Participant 6 likes the fact that she has to go to the hospital for check-ups more often. It gives her a feeling of safety. It is, however, sometimes difficult to find time for the appointments:

‘I’m a mother of two young children. This requires a lot of energy and it’s not always easy to find time for the check-ups. Fortunately I have a lovely husband who takes care of the children when I’m in the hospital. Before I decided to participate in this trial, I talked about it with him. He was very supportive. I don’t know whether I would have participated if he was against it. I don’t think so. Nowadays he still is very supportive. This motivates me to continue.’

Participant 6 does not know the clinical trial is sponsored by a pharmaceutical company. She thought the trial was conducted by the hospital. She mentions that she cannot be bothered by the reputation of the pharmaceutical industry. When asked if she has ever seen advertisements for clinical trials, the answer is yes. She thinks the use of advertisements could be a powerful recruitment tool:

‘A lot of patients are interested in new treatment methods, but their physician doesn’t always inform them about it. Advertisements on websites of patient associations could inform people about new treatment methods and motivate them to participate in a clinical trial.’

Participant 6 is participating in this trial since 2009. She is very satisfied with the execution of the trial:

‘My internist and the research nurses are very nice to me. They listen to me and often say that they appreciate the fact that I participate in this trial. I’ve known them for quite a while and I have a good relationship with them. Because I like them so much, I don’t mind going to the hospital for check-ups. This morning I got a little present from them. I really liked it; it gives me the feeling I’m not doing all this for nothing.’

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17 Participant 7

Gender: Female Age: 49 Region: Utrecht Clinical trial: Trial B

In 2009, participant 7 went to the hospital, because she had some indefinable pain in one of her breasts. Her internist discovered that she had a benign tumor in one of her breasts. Shortly after, he asked her if she wanted to participate in a clinical trial:

‘When my internist asked me for this clinical trial, I didn’t know whether I wanted to participate. I’ve always done volunteer work and when I get the opportunity to help other people, I usually do this. However, there were some risks, so I was a bit scared. Eventually, after I’d read the informed consent and had a discussion with my husband, I decided that I wanted to participate. My husband supported my decision. If he was against it, I wouldn’t have participated.’

Participant 7 thinks the written information was well-organized, clear, and understandable. In addition, she experienced the conversation with her internist as very pleasant. However, that was not the reason why she decided to participate:

‘I wanted to participate in this trial to help other people. I’m not doing this for my internist.

Although he explained the ins and outs of the trial really well, he didn’t ‘talk me into’ this trial.’

When asked if participant 7 would also have participated in the clinical trial if a research nurse had asked her, the answer is yes.

‘I don’t care if a physician or research nurse asks me for a clinical trial. They both know more of the medical world than I do. I think a research nurse is capable enough of asking these types of questions.’

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Participant 7 is aware of the fact that the clinical trial is executed by a pharmaceutical company. She says this did not withdraw her from participating in this trial. When asked if she thinks it is a good idea to use advertisements as a recruitment tool, the answer is no:

‘For these types of questions a personal approach is very important. I think the patient- physician relationship plays an important role in the process, so I don’t think it’s a good idea to replace this personal approach by placing advertisements. It’s very impersonal and I wouldn’t participate in a clinical trial after seeing an advertisement.’

So far, participant 7 is very satisfied with the execution of the clinical trial. She has developed a good relationship with the members of the study team:

‘I don’t mind that I have to go to the hospital more often. The members of the study team are very nice to me. Two weeks ago, I celebrated my birthday and they even sent me a birthday card! I appreciate this. It indicates that they’re interested in my personal life and care about me. This motivates me to continue with this trial.’

Participant 8

Age: 44

Clinical trial: Trial C

Participant 8 was diagnosed with diabetes mellitus 2005. As a result, she was referred to an internist. After a year, her internist asked her if she wanted to participate in a clinical trial. She had to think about it:

‘When my internist asked me to participate in a clinical trial, I didn’t know what to do. I didn’t want to disappoint my physician, because I have a good relationship with him, but at the same time I was a bit scared, because I didn’t want to be treated a guinea pig.

Fortunately, my physician understood my concerns and he did everything to reassure me. He took a lot of time to explain the ins and outs of the trial and he told me it wouldn’t be a bad

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thing if I decided not to participate in this trial. I think he handled this conversation really well and shortly after I decided that I wanted to participate in this clinical trial.’

The conversation participant 8 had with her physician and the reputation of her physician were the tie-breaking factors in her decision to participate in the clinical trial. She also got an information package in which the benefits and risks of the trial were explained, but she has not read this package in detail:

‘I didn’t feel the need to read the information package in detail. I knew what I was doing, because my internist explained the ins and outs of the trial. Moreover, the information package was quite long and I didn’t understand every word of it. It wasn’t very inviting to read.’

Participant 8 attaches importance to status and would not have participated in the clinical trial if a research nurse had asked her or if she had seen an advertisement. She doesn’t believe in advertisements either. She elaborates on this as follows:

‘I have faith in my physician. For me, a research nurse serves as an assistant. This person doesn’t have same amount of medical knowledge my physician has. So no, I wouldn’t have participated in this trial if the research nurse had asked me. This is the task of the physician.

That is why I don’t think it’s a good idea to use advertisements as a recruitment tool. It’s very impersonal and I think it’s difficult to reach the target group.’

When asked if participant 8 discussed her participation in the clinical trial with other persons, the answer is yes. She had a conversation with her husband. He was not very supportive, because he associated participating in the trial with high risks:

‘My husband was not very happy about me participating in the trial. He decided to call my internist. He explained the most important things of the trial to my husband. After this conversation, he was much more supportive and understood why I wanted to participate in the trial. I’m glad my physician was able to reassure my husband, because I don’t think that I would have participated if my husband was against it.’

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Participant 8 is participating in this trial for a few years now. She is very satisfied and is happy with all the extra attention she gets:

‘The members of the study team are very nice to me. I don’t mind that I have to go to the hospital more often than normal, because I love talking to them. Moreover, I get a reimbursement for my travel expenses. I knew this up front and it makes participating in this trial much easier. Sometimes I talk about the trial with family and friends. They are very supportive. This keeps me motivated to continue.’

Participant 9

Age: 58

Participant 9 was diagnosed with diabetes mellitus in 2003. In February 2005, his internist asked him if he wanted to participate in a clinical trial for diabetes mellitus patients. At that time, he had known his internist for quite a while:

‘My internist is a decent, honest guy. He has a good reputation; everybody in his waiting room is positive about him. When he asked me for this clinical trial, I didn’t have to think about it. I’ve known my internist for a long time and he’s always been nice to me. He treats me with respect. Participating in this clinical trial had several advantages. I’ve always done volunteer work and by participating in this trial, I can help several other people. It also gives me a feeling of safety. I knew there were some risks, but the advantages of participating were more important for me than the disadvantages.’

Participant 9 is not very positive about the written information he received. He thinks his internist informed him very well, but the informed consent (the written information) was too long and sometimes difficult to understand. He would not have participated in the clinical trial if the informed consent was the only source of information. When asked if participant 9 would also have participated if a research nurse asked him, the answer is yes:

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‘I don’t care if a physician or research nurse asks me to participate in a clinical trial. I think they’re both qualified enough to ask these types of questions. I think it’s more important how they explain the ins and outs of the trial. They have to be patient and don’t try to rush explaining everything.’

Before he decided to participate in the clinical trial, participant 9 talked about it with his wife.

She encouraged him to participate in this trial:

‘I’m glad that my wife supported me. I don’t know if I would have participated in this trial if she didn’t support me, because I don’t like having arguments with her. Nowadays she is still supporting me. We sometimes talk about the trial and she always says she’s proud of me. This motivates me to continue.’

When asked if participant 9 thinks it is good idea to place advertisements to recruit patients for clinical trials, the answer is yes. He thinks the use of advertisements increases people’s awareness of clinical trials and says he would respond to it if he thought he would meet the inclusion criteria.

Participant 9 gets a reimbursement for travel expenses, newsletters and sometimes a little gift.

He knew this up front and thinks these little extras could influence a patient’s decision of whether to participate in a clinical trial:

‘For me, these extras were not the main reason to participate in this trial. It is, however, important to give the patients these extras. It makes it easier to participate. Moreover, these extras keep me motivated to continue with the trial.’

Regarding the execution of the clinical trial, participant 9 has the following to say:

‘I’m very satisfied with the execution of the trial. The members of the study team are very nice. We laugh a lot and they respect me. I’ve known them for quite a while. I’m not saying that we are friends, but I do think I’ll miss them once I’ve finished the trial.’

Participant 10

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Age: 74

At the beginning of 2004, participant 10 was hospitalized because he did not feel very well.

After some examinations, the physicians discovered that participant 10 suffered from type 2 diabetes mellitus. As a result, he was referred to an internist. In 2005, the internist asked him if he would be interested in participating in a clinical trial for type 2 diabetes mellitus patients.

At that time, participant 10 had known his physician for more than a year and had a close relationship with him:

‘My internist is a nice, honest guy. He knows I’m not a big fan of hospitals, so when I visit him, he always tries to reassure me. I know some of his other patients as well. He has a good reputation, because everybody is very positive. When he asked me for this trial, I didn’t have to hesitate. My internist knows what’s best for me and if I can help him by participating in this trial… well… why not?’

Participant 10 is satisfied about the information he received. His physician explained the trial in detail and the informed consent was well-organized and clear.

Before participant 10 decided he wanted to participate in the clinical trial, he talked about it with his wife:

‘My wife and I have been together for thirty years. I discuss everything with her. Fortunately, she supported my intended participation. We have always done volunteer work and helping other people is one of our goals in life.’

Participant 10 attaches importance to status and knowledge. He would not have participated in this clinical trial if a research nurse had asked him. When asked if participant 10 thinks it is a good idea to use advertisements as recruitment tool, the answer is no:

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‘I believe in a personal approach.. It’s very impersonal and the amount of information is often minimal. Most of these advertisements do not look very appealing either. That’s why I don’t think advertisements will initiate a patient’s interest to participate in a clinical trial.’

Participant 10 is aware of the fact this clinical trial is executed by a pharmaceutical company.

He is quite positive about the pharmaceutical industry and does not agree with the statement that the pharmaceutical industry cares about profits only.

Participant 10 is satisfied with the execution of the trial:

‘I’m very happy that I decided to participate in this trial. The members of the study team are very nice. They’re doing everything to make participating as easy as possible. I get a travel allowance and sometimes they give me little gifts. I appreciate this, it’s a nice gesture.’

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Appendix 4 – Expert Interviews

Professional 1

Profession: Cardiologist

Professional 1 has been a cardiologist for 25 years. He started his career in the pharmaceutical industry at a Clinical Research Organization (CRO). In 1995, he started working as a cardiologist in a mid-sized hospital in Rotterdam. He has executed several trials in the field of atrial fibrillation, hypertension, and angina pectoris:

‘I believe the physician plays an important role in a patient’s decision of whether or not to participate in a clinical trial. If a patient trusts his or her physician and is loyal towards this person, chances are high that this patient will participate in a clinical trial. It is important that physicians create a strong relationship with their patients. This might take some time, but it makes the recruitment process much easier.’

Professional 1 experienced that recruiting patients for clinical trials is rather difficult:

‘Recruiting patients for clinical trials is a difficult and time-consuming process. It is hampered by the fact that the one who prescribes the medicine, the one who pays the medicine, and the one who uses the medicine are not the same person. There are three groups of people involved and they all have different values. In addition, most patients associate participating in a clinical trial with high risks. Especially when it doesn’t benefit them, they don’t see the point of participating. Besides recruiting patients, it is also difficult to keep patients motivated to finish the entire trial. It happens quite often that patients decide not to continue with the trial. This could be the case when they suffer from severe side-effects or when the check-ups take too much time. ‘

In order to reduce churn rates, professional 1 decided to introduce retention materials.

Examples of such materials are patient newsletters or little gifts such as candy or Christmas

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cards. He believes these materials motivate patients to continue participating in the clinical trial:

‘I think it’s important that we show patients that we respect them and that we appreciate the fact that they’re participating in one of our trials. That is one of the reasons why we decided to introduce patient newsletters. In these newsletters, patients can read how much patients participate in the trial worldwide and how the inclusion is going. In addition to the newsletters, we also give our patients little extra’s. For example, last Christmas, we have sent our patients a Christmas card.

However, handing out these retention materials is not enough. The physician and research nurses play an important role as well. They have to be nice to the patients and keep them satisfied. I believe that when a patient has a good relationship with the members of the study team, he or she is more willing to continue participating in the clinical trial.’

Professional 2

Profession: Neurologist

Region: Breda

Professional 2 has been a neurologist for twenty years. He is working in a mid-sized hospital in Breda. Professional 2 has supervised several clinical trials in the field of multiple sclerosis, the Alzheimer disease, and epilepsy. He believes that the information package patients receive often influences one’s decision of whether or not to participate in a clinical trial. He explains how he recruits patients for a clinical trial, by elaborating on this as follows:

‘First, I make a list of patients who meet the inclusion criteria of the clinical trial. When one of these patients visits the hospital for a check-up, I ask this person if he or she is willing to participate in a clinical trial. I tell them that the goal of such a trial is to discover new treatment methods. I don’t give them a lot of details, because I don’t want to overrun them with information. If the patient is positive, I send him or her an information package by mail.

After a week or so, I call them to ask what they think of the trial. It happens quite often that patients decide not to participate after they have read the content of the information package.

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I think that the information package includes too much information. In addition, the content of the information package scares patients, because every potential side effect of the medicine is explained in detail. I try to overcome these drawbacks by telling patients that I wouldn’t have asked them for the clinical trial if I thought it would be too dangerous. This often reduces a patient’s feeling of being at risk. I also explain to them why participating could be beneficial.

After all, most people want to know what is in it for them.’

Besides asking his own patients, professional 2 sometimes makes use of advertisements.

Although he believes that it is best to ask patients in person, he thinks that advertisements could initiate the interest in participating in a clinical trial. He elaborates on this as follows:

‘I think that advertisements could work, as long as the inclusion criteria are mentioned. It is not desirable to have people responding to an advertisement who don’t meet the inclusion criteria. This is a waste of both time and money.’

Professional 2 thinks the relationship between the physician and the patient greatly influences a patient’s decision of whether or not to participate in a clinical trial. In general, professional 1 believes that the longer a patient has known his or her physician, the more willing he or she is to participate in a clinical trial:

‘I think it’s really important to have a good relationship with your patients. It’s much easier to ask a patient for a clinical trial if you have known this person for a while. These people respect me, value my opinion, know that I have an honorable reputation, and often decide to participate in the trial in order to please me. This is especially true for patients who live in the south of the Netherlands. These people value the opinion of a physician and are less difficult than people originating from Amsterdam or Rotterdam. I also believe that both the depth and length of the patient-physician relationship influence patient retention rates. The majority of the patients that I have known for quite a while don’t quit, because they don’t want to disappoint me.’

Professional 2 does not think it would be a good idea to let research nurses do the recruitment.

According to him, research nurses do not have the same amount of supremacy and trust that a physician has:

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‘I think it’s the task of the physician to ask a patient for a clinical trial. The role of the physician is crucial. I often notice that my patients have more trust in me than in my research nurses. That is why I always contact the patients myself.’

In addition to the role of the physician, professional 2 believes that family members and friends also influence a patient’s decision of whether or not to participate in a clinical trial. He thinks that it is very important to get family members and/or friends involved with the trial. It is important that these people are well informed in order to prevent the thought that their beloved one will be treated as a guinea pig.

Professional 2 does not think that the negative reputation of the pharmaceutical industry influences the decision of a patient on whether or not to participate in a clinical trial. He thinks that the majority of the patients do not know that the clinical trial is conducted by a pharmaceutical company.

With regard to patient retention, professional 1 has the following to say:

‘The majority of the patients who participate in a clinical trial finish the entire trial.

Sometimes people decide to quit because of the side effects, but this doesn’t happen a lot. I’m always nice to the patients and encourage them to continue by saying that they are doing a good job. We, as a study team, are doing everything we can to make participating as convenient as possible, as satisfied patients are more willing to finish the entire trial. Patients always get a cup of coffee, travel reimbursements, and the check-ups are scheduled at times that are convenient for the patient. Once a year, I organize a concert to thank all the patients for their contribution. They really appreciate this. Although the majority of the patients appreciate these extras, it should not be the main reason for a patient to participate in a clinical trial. That is why we do not tell this to them up front.’

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Profession: Research nurse

Region: Breda

Professional 3 has been a research nurse for eleven years. She is working in a mid-sized hospital in Breda and has been involved with the execution of several clinical trials in the field of internal medicine and neurology. Professional 3 is responsible for several things: she makes sure that all study documents are handed in at the medical ethics committee, she explains the content of the clinical trial in detail to the patient (if the physician does not have time for that), she is the first contact person for patients, she conducts patient check-ups, and she does all the administration that accompanies the study. She explains that it is sometimes difficult to recruit patients for a clinical trial:

‘Not every patient is willing to participate in a clinical trial. Some patients are afraid of the side effects and some just don’t see the point of participating. The information packages that we have to give to the patients are not always understandable. Most of the time, the package contains 20 pages of information and all the risks and potential side effects are explained into detail. The focus on potential benefits is nil. This scares people off and indicates that the transfer of information, in this case information regarding both potential risks and benefits, plays an important role in the patient decision process.

If we are behind schedule in the recruitment of patients, we place advertisements. This is a useful tool, as the response rate is often quite high. Although I see advertising as a powerful tool, it has one major disadvantage. We often notice that a lot of people who do not meet the inclusion criteria of the clinical trial still respond to the advertisement. This costs time and money.’

Professional 3 thinks it is important that the physician asks the patient for the trial himself.

She has asked some patients herself, but experienced that most people are more entitled to the opinion of a physician:

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‘Most patients are very committed to their physician. They respect this person and have the feeling that he or she knows what’s best for them. I think that it is the task of the physician to ask a patient for a clinical trial. It is important that the physician takes enough time to explain the trial and is open for answering questions. If he or she does not have that time and patience, we can explain the details of the clinical trial to the patients. However, I think this is the task of the physician, as most patients presume everything he or she says as true. That is not the case when we give an explanation of the clinical trial.’

Professional 3 believes that, besides the relationship patients have with their physician, family members also play an important role in the patient decision process:

‘I have noticed that the majority of the elderly involve family members in their decision of whether or not to participate in the clinical trial. If their husband or children don’t support their participation, they often don’t want to participate. Younger people are more independent. They search for information on the internet, instead of asking family members or friends for their opinion.’

‘I always encourage patients to finish the entire trial. I thank them for coming to the hospital and I schedule the check-ups at a time that is convenient for them. I think it is very important to give them enough attention to keep them satisfied. If a patient becomes a grandparent or celebrates his or her birthday, I often send this person a card. In this way, we (read: the study team) develop a strong bond with the patient, which makes it more difficult for a patient to quit the trial.

In addition to the personal attention, we give patients brochures, little gifts or a reimbursement for travel expenses. You should not overdo this, but I have noticed that the majority of the patients appreciate this. We do not tell this up front, because this should not be the main reason to participate in a trial.’

Professional 3 thinks that the negative reputation of the pharmaceutical industry sometimes influences the patient’s decision process. According to her, some patients refuse to participate

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in a clinical trial, as they have the feeling that the pharmaceutical industry uses them as so- called guinea pigs to make enormous amounts of money.

Professional 4

Profession: Research nurse

Region: Zwolle

Professional 4 has been a research nurse for four years. She is working in a mid-sized hospital in Zwolle. Professional 4 has executed clinical trials in the field of cardiology and oncology.

She also worked with diabetes mellitus patients. Professional 4 is responsible for submitting new amendments at the medical ethics committee, assisting the physician for the execution of the clinical trial, and the administration. She thinks the physician plays an important role in a patient’s decision of whether or not to join the clinical trial:

‘I think the physician should ask a patient for a clinical trial. I’ve experienced that most patients see their physician as holy, especially if they’ve known this person for a while. They often say ‘yes’ to a clinical trial, because they don’t want to disappoint their physician. In addition, they want to maintain the good relationship with this person. I also believe the reputation of the physician could influence recruitment rates. Patients who consider the reputation of their physician as ‘good’ are often more willing to participate in a clinical trial than patients who do not know what the reputation of their physician is. But I have to say, though, that the quality and length of the patient-physician relationship is much more important that a physician’s reputation.’

Besides the role of the physician, professional 4 believes that the transfer of information also plays an important role in the patient decision process.

‘We pay a lot of attention to informing the patient. If the physician does not have enough time to inform the patient about the ins and outs of the clinical trial, we perform the task of

‘informer’. It is important that you spend enough time on informing the patient. The patient has to understand every aspect of the trial. I think it’s important they know what’s in it for them. This prevents disappointments and diminishes the amount of perceived risk.’

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Professional 4 has noticed that most patients discuss their intended participation with family members or friends:

‘Most patients first want to discuss the ins and outs of the trial with their family members or friends before they decide to participate. It’s very important that these persons support the patient. It happens quite often that patients decide not to participate in a clinical trial, because their husband, wife or kids are against it. I try to overcome this by talking to the family members and reassure them.’

Professional 4 believes advertisements could be a powerful recruitment tool, if they are used the right way. She does not prefer using advertisements and thinks a personal approach works much better. However, sometimes it is very difficult to find enough patients that meet the inclusion criteria of the trial. When this is the case, placing advertisements could be a good option.

Professional 4 thinks the negative image of the pharmaceutical industry could influence recruitment rates as well:

‘Most patients associate the pharmaceutical industry with high profits. Some patients therefore refuse to participate in clinical trial, because they don’t want to be part of that.’

‘It is very important that the members of the study team respect the patients. Without them, we wouldn’t have a job. I do everything to keep the patient as satisfied as possible. Satisfied patients are more willing to finish the entire trial than dissatisfied patients. In addition, I believe it’s important to create a bond with the patient. Of course, this bond should not become too personal, but there is nothing wrong with asking patients about their personal life. We sometimes hand out little gifts as well. Most patients are very happy with this gesture, it gives them the feeling of being appreciated and motivates them to finish the entire trial.’

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Appendix 5 – Questionnaire for participants

Dear Sir/Madam,

In order to finish my master Marketing Management at the University of Groningen, I am currently carrying out a research project for sanofi-aventis. Sanofi-aventis is a company that produces medicines. To be able to product medicines, clinical trials are held. Clinical trials are research studies in which both healthy volunteers and patients help physicians find ways to improve health care.

The goal of my research is to discover why people participate in clinical trials and what their experiences with participating in such trials are. You are participating in the NAME OF THE CLINICAL TRIAL at the moment. Because everyone has their own reasons to do so, your answers to this questionnaire are very helpful to my research.

This questionnaire is sent by an employee of the NAME OF THE HOSPITAL. Participating is entirely voluntarily and your answers to the questionnaire will be used for statistical purposes only. The questionnaire consists of a number of multiple choice questions and statements. Completing the list takes approximately 10 to 15 minutes. If an item is irrelevant to you or you do not know the answer, please leave the checkbox blank.

This questionnaire is accompanied by a pen. You can keep this pen; is sent to you as a thank-you for your participation.

Thank you very much for your cooperation!

Kind regards,

Lisanne Buijsse

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1) How did you hear about the NAME OF THE CLINICAL TRIAL?

I saw an advertisement for this clinical trial in the newspaper I saw an advertisement for this clinical trial on the internet My treating physician told me about this clinical trial

A researcher, who was not my treating physician, told me about this clinical trial A research nurse told me about this clinical trial

Other, namely:

I don’t know

2) Not every person can participate in a clinical trial. Your physician will first examine whether you meet the inclusion criteria of the clinical trial. Subsequently, your physician or research nurse asks if you are interested in participating in this clinical trial. Who asked you for this NAME OF THE CLINICAL TRIAL?

My treating physician (go to question 3) A researcher (go to question 3)

A research nurse (go to question 4)

Someone else, namely: (go to question 4)

I don’t know (go to question 4)

3) Would you also have participated in the NAME OF THE CLINICAL TRIAL if a research nurse had asked you?

Yes No Maybe

I don’t know

The next three questions are for respondents who were asked by their physician or research nurse for the NAME OF THE CLINICAL TRIAL. Respondents who were asked by a researcher for the NAME OF THE CLINICAL TRIAL can continue with question 7. From question 7 on, the questions will apply to the physician and/or research nurse. In your case,

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4) The next statements are on the relationship you have with the person who asked you to participate in the NAME OF THE CLINICAL TRIAL (so your physician or research nurse). Please circle the answer that applies to you.

I am satisfied with my physician/research nurse

Totally disagree 1 2 3 4 5 Totally agree

My physician/research nurse is friendly

I have faith in my physician/research nurse

My physician/research nurse puts my interests first

The relationship I have with my physician/research nurse means a lot to me

5) For this question it is important that you go back to the moment that your physician or research nurse asked you to participate in the NAME OF THE CLINICAL TRIAL.

For how long were you treated by your physician or research nurse at that time?

Less than 6 months Between 6 and 11 months Between 1 and 3 years Longer than 3 years I don’t know

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6) The next three statements are on the reputation of the person who told you about the NAME OF THE CLINICAL TRIAL (so your physician and/or research nurse). Please circle the answer that applies to you.

My physician/research nurse has a good reputation

My physician/research nurse cares about his or her patients

My physician/research nurse is known for being honest at all times

7) Before you decided to participate in the NAME OF THE CLINICAL TRIAL, you received some information about the clinical trial from your physician and/or research nurse. The next statements are about the information you received regarding the NAME OF THE CLINICAL TRIAL. Please circle the answer that applies to you.

The information I received about this clinical trial was easy to understand

The information I received about this clinical trial was well-organized

The information I received about this clinical trial was complete (that means, you did not miss any information)

I received too much information about this clinical trial

1 2 3 4 5

I received too little information about this clinical trial

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8) Before you decided to participate in the NAME OF THE CLINICAL TRIAL, you had a conversation with your physician and/or research nurse in which he or she told you about the clinical trial. The next statements are on this conversation. Please circle the answer that applies to you. Keep in mind the person with whom you had the conversation (so your physician and/or research nurse).

My physician and/or research nurse told me a lot about this clinical trial

My physician and/or research nurse was able to answer all my questions regarding the clinical trial

My physician and/or research nurse listened carefully to the remarks and/or questions I had about this clinical trial

My physician and/or research nurse took enough time to explain the ins and outs of the clinical trial

During the conversation, my physician and/or research nurse treated me with respect

During the conversation, my physician and/or research nurse gave me enough freedom of choice in whether to participate in the clinical trial or not

9) Did you, when you were asked for the NAME OF THE CLINICAL TRIAL, receive information about additional arrangements that would make participating in the clinical trial easier (for example a travelling allowance)?

Yes, go to question 10 No, go to question 12