5.1 Introduction
This chapter outlines and discusses the methods used in this study. Details relating to the site access and recruitment are provided. This is followed by a discussion and outline of the methods chosen for data collection and the decisions that influenced their selection. Data were collected on seven different occasions from participants in this study; the reasons for this are provided in section 5.9. The process for managing the data using SPSS Version 15 and NVivo 7 will be outlined and the statistical tests used for quantitative data analysis will be identified along with a rationale. A pilot study was conducted and issues and developments arising from it relating to the main study are outlined. Ethical approval and issues relating to this study are outlined and discussed. This is followed in the last sections by a description and discussion of the quality initiatives and the use of independent monitoring of data in this study. It is important to note that this is an interim analysis, therefore, findings should be viewed tentatively as they may not reflect the final results. Also, it is not appropriate to comment on accepting or rejecting the null hypothesis at this stage as the a priori sample size has not been achieved. One advantage of conducting interim analysis is that the results can be reviewed by the independent monitoring person in order to determine whether or not the study should continue. A significant result at this interim stage would indicate either sufficient benefit of one intervention in one instance or evidence of harm in another, usually resulting in the need to stop the trial.
5.2 Ethical Approval
This study was reviewed by the ethics advisory committee of the School of Nursing and Midwifery, Trinity College Dublin, and received ethical approval from the hospital’s Research Ethics Committee (Appendix 11).
5.3 Negotiation of Access
Access to the research site and permission to conduct the ‘Open Window’ study was sought from the Hospital’s chief executive officer, the director of nursing, the relevant hospital consultants and the nurse managers of the stem cell transplant unit. The director of this study is also the director of the transplant unit, therefore permission to conduct the study on the unit was implicit and included permission and support from the other relevant consultants. Gaining permission from the nurse managers in the unit was also straightforward as they were involved in the introduction of ‘Open Window’ to the unit. Permission from the hospital’s chief executive officer and the director of nursing was obtained through the Patient Advocacy Committee (Appendix 12). The patient advocacy committee is a quality initiative within the hospital with external and internal organisational members. The purpose and membership of this committee will be discussed in more detail under the section ‘Quality Initiatives’ at the end of this chapter.
5.4 Recruitment
There were a number of issues to consider when developing a recruitment process that was effective and efficient for all concerned. The first issue was that all patients undergoing stem cell transplantation (autologous and allogeneic) would need to complete a Trial Registry Form (Appendix 13) whether they agreed to participate or not. If the patient was eligible and agreed to participate in the study, they would then need to provide verbal and written consent. The people regarded as best placed to do this were the two transplant co-ordinators attached to the unit. They see all patients on a number of occasions prior to their admission and know the patients well. They agreed that they would complete the Trial Registry Forms, administer the patient information leaflet (Appendix 15) and if necessary answer any queries, and take consent if the patient wished. They would then inform me of the names of patients who had provided consent (verbal
or written) and forward the trial registry forms to me and I proceeded with the randomisation process (see flow chart, appendix 14). Once successfully recruited, stickers were placed on the front of the participants’ charts stating the name of the study and their study number.
If a patient was regarded by the transplant co-ordinator as being too anxious to recruit to the study at the time of their visit to the transplant co-ordinator, they informed me and I contacted the patient by telephone a few days later. If they expressed an interest in participating in the study, I forwarded the information leaflet and consent form by post. On receipt of verbal or written consent I contacted the telephone randomisation service who issued a study number and gave the allocation of the patient.
An important part of the recruitment process being successful was training the transplant co-ordinators. This took the form of a number of meetings with me in which we discussed the overall study protocol, the patient information sheet and consent form. They were both very familiar already with the ‘Open Window’ project in the unit before the study started and were familiar with the study documentation, particularly the patient information sheet and consent form, as I had sought their contribution and feedback in the development of these documents. Both co-ordinators also had experience in recruiting patients for studies in the past and they assured me that this would not be a difficult process for them. Furthermore, the number of patients eligible and willing to participate in studies with a similar population and context is between 70% and 100% which is quite high (Keogh et al. 1998, Kiss et al. 2002, So et al. 2003, Hayden et al. 2004) thus contributing to their ultimate goal of recruiting 400 patients to the study. This is in contrast to a review of 35 papers exploring why patients do not take part in cancer clinical trials by Cox and McGarry (2003), which identified low accrual rates of between 2-5% in the both the United States and the United Kingdom. The reason for the higher accrual rates in studies with stem cell or bone marrow transplant patients may be that they are usually feeling very well
when admitted to hospital and therefore, do not perceive participation as a burden.
However, I was eager to discuss the issue of bias in recruiting participants for this study in particular in relation to the co-ordinators’ personal views and experiences of both art and the use of technology. For example, they may have felt that women would be more responsive to art, therefore, they may expend more time and effort in recruiting them. I felt that through informal guided discussion, I could facilitate a reflective process in which the co-ordinators would become aware of their own views on this and in recognising also, the possibility of an unconscious bias being reflected in their recruitment styles, they would be more aware of how they recruited, thereby limiting or eliminating bias. Informal discussions continued throughout the recruitment process in order to ensure that the recruitment guidelines were followed and to maintain awareness of the possibility of bias in how patients are recruited.
On a number of occasions, the transplant co-ordinators had very limited or no one-to-one contact with patients before they were admitted for transplantation. On these occasions I phoned the patients directly and discussed the study with them. This was successful, with all patients agreeing to take part in the study verbally, thus allowing the randomisation process to take place before the patient arrived on the unit. I anticipated that some participants may have changed their minds about participating in the study on the day of admission, but, this was not the case. All patients showed enthusiasm and appeared interested and happy to contribute. Recruitment for this study was not problematic and the main reason for this was that when patients are admitted for bone marrow transplantation, they are probably feeling better physically and even psychologically than in the previous few months, and were, therefore, more likely to consent to participating in the study. For this reason it was important that consent be an ongoing process as dramatic changes in physical and psychological well-being could be expected undergoing treatment of this kind.
5.5 Informed consent
When eligible patients were being recruited to this study, either I or the transplant co-ordinators gave them a patient information leaflet (Appendix 15), discussed the study with them and answered any questions. Each patient had approximately 5 days to consider the information and decide if they wished to participate in the study. They were also given the opportunity to discuss the information with me if they wished and my contact details were provided on the leaflet. If they agreed to participate they were asked to provide written consent on admission to hospital or before admission if feasible. They signed two copies of the consent form (Appendix 16), which were co-signed by me or the relevant transplant co-ordinator. Participants were made aware at this point that this was not binding and they could withdraw their consent to participate at any time without explanation.
Patients over the age of 16 were eligible to participate in this study. Verbal and written consent was required from the patient and parents if they were between the age of 16 and 18yrs. In the event of this happening, it was planned that I would meet the patient and parent(s) and discuss the study in detail; however, this has not been necessary up to this point in the study as all prospective participants have been above 18 years of age.
5.6 Randomisation
Randomisation is a process that ensures that each participant in a study has equal chance of being assigned to either the intervention or control group (Friedman et al. 1998, Beller et al. 2002, Schultz and Grimes 2002). Randomisation comprises two key processes, the first is the generation of a randomised allocation schedule that is unpredictable and the second is concealment of the sequence until the point of allocation (Schultz and Grimes 2002). The process should prohibit either the potential participant or the people recruiting participants knowing what
the patients’ allocation is before they agree to participate in the study. Schulz and Grimes (2002) and Beller et al. (2002) suggest that the person who generated the random allocation sequence should not be involved in recruitment, administering the intervention or evaluating the outcome. The allocation sequence for this study was generated using a computer random number generator package (StatsDirect).
Random allocation of the participants in this study was conducted by a telephone randomisation service. When patients were recruited to the study by the transplant co-ordinators they informed me and I then contacted the telephone randomisation service. In order to conceal the random sequence to the point of allocation, it would have been more appropriate for the transplant co-ordinators to contact the telephone randomisation service directly when the patient provided consent. However, due to operational difficulties this was not feasible. The person located at this service and who allocated the participant and assigned the study number was independent physically and professionally to the study site and researcher respectively. This reduced the chance of selection bias in allocating patients (Friedman et al. 1998, Roberts and Torgerson 1999, Devane et al. 2004). The person at the telephone randomisation service allocated the participant’s study number and group from a predetermined list. The telephone randomisation service also maintained a record of the date, time, person requesting the randomisation, and hospital identity number (Appendix 17) of each participant.
Simple, blocked and stratified are three approaches to fixed allocation. Simple randomisation is unrestricted and described by Schulz and Grimes (2002) as the ultimate method of ensuring unpredictability and preventing bias. However, they also suggest that its ability to provide truly unpredictable sequences can be disadvantageous because it can cause highly disparate sample sizes in groups. Although this imbalance dissipates with larger sample sizes (≥ 200) and towards the end of recruitment, it can be problematic if the researcher needs to conduct interim analyses. In view of this, Schulz and Grimes (2002) and Friedman et al.
(1998) propose that randomisation should be balanced or restricted and this is achieved through blocking. This process guarantees that large imbalances in group sizes will not occur by ensuring that after blocks of every 4, 6 or 8 participants are randomised, the groups are equal in size. Blocking has the ability to limit the predictability of the allocation sequence greatly, but it is still possible, particularly in larger unblended studies for staff involved in recruiting participants to recognise patterns of allocation. The use of larger block sizes or randomising block sizes can prevent this by making it more difficult to determine where a block starts or stops (Friedman et al. 1998, Schultz and Grimes 2002).
Participants in this study were allocated a study number and randomly assigned to the intervention or control group on a 1:1 ratio. A computer random number generator (StatsDirect) used random block sizes to produce the allocation sequence for this study. Due to the expected differences in responses between sub groups A and B and sub groups C and D, randomisation was stratified. It is arguable that allocation should be unequal, that is, more participants should be allocated to the intervention than control group, for example on a 2:1 ratio. The advantage of this is that more information may be obtained in relation to the intervention, but according to Friedman et al. (1998) this could result in participants being exposed to an ineffective or even harmful intervention needlessly. Equal allocation of participants to intervention and control groups was chosen for this study because it is the more powerful design (Friedman et al. 1998) and is also reflective of equipoise or the researcher’s belief that the anticipated effect of ‘Open Window’ is unknown.
Random allocation of participants in this study required teamwork and co- operation between the research team and the nursing/medical staff on the transplant unit. The reason for this is that patients are cared for in single rooms under very restricted conditions in order to prevent infection. Ensuring that participants who were randomised to the intervention group were admitted to a room with ‘Open Window’ sometimes required moving a patient to another room
in order to vacate the appropriate one. While this in itself is a straightforward process, each room that is vacated needs to go through a rigorous cleaning process before another patient can occupy it. Therefore, it requires planning on behalf of the nurse manager and can be disturbing for patients who are asked to move to another room. In order to minimise disruption for patients and the nursing staff, the randomisation process was conducted a minimum of 3 days before the patient was admitted. This meant that the nurse manager and relevant staff could be prepared in advance to move patients when necessary.
5.7 Pilot Study 1
Unforeseen problems may arise when conducting a research project, resulting in the need for changes to be made to the study protocol. In experimental studies, if changes are made after the main study has started, all data collected prior to this cannot be included in the study. Polit et al. (2001) recommend that the researcher conduct a small-scale trial run of the main study, the purpose of which is to identify problems related to the study methods and feasibility (Polit et al. 2001). Therefore, a pilot study for this research project was conducted during July-October 2005. Six patients undergoing allogeneic stem cell and bone marrow transplantation were recruited with three randomly allocated to both the control and intervention groups. This was a small sample size due to time limitations. Over the three month period of the pilot study it was vacation time, therefore, the number of patients admitted for stem cell or bone marrow transplantation was somewhat reduced.
5.7.1 Establishing relationships
Prior to conducting the pilot study I held informal information sessions on the ward as I felt that it was important that the staff understood the nature of the ‘Open Window’ study. Although the nursing managers supported this initiative, attendance at the sessions was poor. Subsequent conversations with nursing management and staff nurses revealed that attending these sessions added to the
staff nurses’ perceptions that the study may increase their workload. On reflection I understood the point and felt that as they were not required to contribute to the study directly, they could be informed about the study in another way. It was important that, although they were not directly involved in the study, they understood the concept and the study process so that they could interact appropriately with the participants when necessary. Therefore, I made posters outlining the concept of ‘Open Window’ and the study details, and placed them in the staff rest room and at both the nurse stations in the unit. The experience of conducting a clinical trial, albeit on a small-scale, was invaluable in allowing me to develop a relationship with the ward staff. In conjunction with the posters, my presence on the ward every day resulted in acceptance and co- operation from the nursing/medical management, staff and cleaning personnel. This was a very positive and important development as the randomisation process in this study created work for the staff in that patients needed to be moved from one room to another on occasion in order to facilitate study participants. When vacated, each room needed to be cleaned meticulously before a new patient could be admitted. It was essential that I used a flexible, understanding and constructive approach to problems that arose in relation to participants being admitted to the appropriate room. I feel that this approach demonstrated understanding of the difficulties the nurse managers faced when ensuring that participants were admitted to the appropriate room and was a key element in maintaining open and positive relations with the ward staff, especially domestic staff.
5.7.2 Recruitment, randomisation, data collection and data management
The pilot study gave me the opportunity to test the recruitment and randomisation system, data collection procedures and to identify data management issues. The recruitment and randomisation procedures ran very well with good communication between me and the transplant co-ordinators in relation to recruitment. However, the issue of informed consent arose as an ethical concern from the pilot study. Although the transplant co-ordinators
recruited the majority of patients for the study, they felt occasionally that some patients would not be able to deal with excessive information during their visits to the day ward due to stress regarding their impending transplant. On these occasions I phoned the patients at home and discussed the study with them. They were asked to think about whether or not they would like to participate in the