Haemophilia (2014), 20, 800–806
DOI: 10.1111/hae.12495
ORIGINAL ARTICLE Clinical haemophilia
Developing a two-sided intervention to facilitate shared decision-making in haemophilia: decision boxes for clinicians and patient decision aids for patients A . A T H A L E , * A . G I G U E R E , † A . B A R B A R A , * S . K R A S S O V A ‡ and A . I O R I O * § *Department of Clinical Epidemiology and Biostatistics, Health Information Research Unit, McMaster University, Hamilton, Ontario, Canada; †Department of Family Medicine and Emergency Medicine, Office of Education and Continuing Professional Development, Laval University, Quebec, Canada; ‡ Medical Director,, Zurich, Switzerland; and §Hemophilia Treatment Center, McMaster University, Hamilton, Ontario, Canada
Background. People with haemophilia face many treatment decisions, which are largely informed by evidence from observational studies. Without evidence-based ‘best’ treatment options, patient preferences play a large role in decisions regarding therapy. The shared decision-making (SDM) process allows patients and health care providers to make decisions collaboratively based on available evidence, and patient preferences. Decision tools can help the SDM process. The objective of this project was to develop two-sided decision tools, decision boxes for physicians and patient decision aids for patients, to facilitate SDM for treatment decisions in haemophilia. Methods. Development of the decision tools comprised three phases: topic selection, prototype development and usability testing with targeted end-users. Topics were selected using a Delphi survey. Tool prototypes were based on a previously validated framework and were informed by systematic literature reviews. Patients, through focus groups, and physicians,
through interviews, reviewed the prototypes iteratively for comprehensibility and usability. Results. The chosen topics were: (i) prophylactic treatment: when to start and dosing, (ii) choosing factor source and (iii) immunotolerance induction: when to start and dosing. Intended end users (both health care providers and haemophilia patients and caregivers) were engaged in the development process. Overall perception of the decision tools was positive, and the purpose of using the tools was well received. Conclusions. This study demonstrates the feasibility of developing decision tools for haemophilia treatment decisions. It also provides anecdotal evidence of positive perceptions of such tools. Future directions include assessment of the tools’ practical value and impact on clinical practice.
Background
haemophilia B [2]. Without intervention, haemophilia manifests itself in recurrent bleeding in joints and muscles, joint arthropathy, and susceptibility to uncontrolled bleeding after external trauma [3]. While there is currently no proven cure, symptoms of haemophilia can be effectively treated with factor replacement therapy using recombinant or plasma-derived FVIII or FIX. Factor concentrates can be infused after a bleeding episode has occurred (on-demand treatment) or to prevent bleeding incidents (prophylaxis treatment)[4,5]. Development of factor inhibitory antibodies, which occurs in 20–50% of previously untreated patients, is a significant complication of haemophilia treatment, because the presence of an inhibitor renders exogenous factor concentrate ineffective [6]. To date, immunotolerance induction is the prefer-
Congenital haemophilia is a rare, genetically transmitted disorder that is characterized by reduced levels of clotting factor VIII (FVIII) in haemophilia A or factor IX (FIX) in haemophilia B [1]. Haemophilia severity is classified by baseline levels of FVIII or FIX. Disease prevalence is estimated at about 1:10 000 cases for severe haemophilia A and a much lower prevalence of Correspondence: Dr. Alfonso Iorio, HiRU, CRL-140, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. Tel.: 905 525 9140 ext 22421; fax: +1 905-526-8447; e-mail: [email protected] Accepted after revision 09 June 2014 800
Keywords: congenital haemophilia, decision aids, intervention, shared decision-making
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ential treatment to eradicate inhibitors in people with haemophilia [7]. Being a rare, chronic disease, research in haemophilia is challenging [8]. Feasibility concerns, such as adequate recruitment and long follow-up times, and methodological challenges, such as difficulty in blinding and unavailability of objective, surrogate outcomes, constitute hurdles in conducting research. Resultantly, there are relatively few randomized clinical trials completed in haemophilia research, and much of the current evidence of the effectiveness of haemophilia treatment options comes from observational, often retrospective, studies, uncontrolled case series, or national and international registries [8,9]. Current research has identified several efficacious treatments options for treatment decisions in haemophilia, such as ideal dosing regimens and starting times of therapy [7,10]. However, without evidencebased indications to unequivocally identify a superior treatment option, uncertainty exists when choosing treatment regimens for patients with haemophilia, and patient preferences play a larger role in the decisionmaking process [11]. Shared decision-making (SDM) is a promising avenue for applying scientific evidence to clinical practice. SDM is a model that helps clinicians and patients make joint health care decisions based on (i) the best available evidence of benefits and harms of treatment options and (ii) patients’ values and preferences in regard to the treatment options [12]. In other clinical fields [13], SDM has been shown to increase the use of the treatment option that is most clearly associated with health benefits [14]. Its use has been associated with a higher quality of life and increased patient satisfaction [15,16]. The SDM process is useful when there are numerous options for a treatment decision, as is often the case in haemophilia. While awaiting formal testing to assess the effects of SDM on clinical outcomes, one can conjecture, based on a purely theoretical basis, that application of the SDM framework to a clinical encounter in haemophilia may improve communication between patients and health care providers and further encourage active participation from both parties in the decision-making process. Decision aids are interventions that help facilitate SDM, and have been used in other clinical areas [13]. While most decision aids are designed for either the patient [13] or physician [17], some decision aid interventions are designed for contemporaneous use by both the clinician and patient [18]. The objective of this project was to create decision tools to inform and facilitate decision-making about treatment options in grey areas of haemophilia management. The decision tool model we have used consists of two tools for each clinical decision– a decision box for physicians and a corresponding patient deci© 2014 John Wiley & Sons Ltd
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sion aid. These tools are intended for use by clinicians and their patients to prepare both parties for a clinical encounter, and are meant to help both parties make joint, informed, value-based decisions about haemophilia treatment. The decision box for physicians and decision aid for patients will be collectively referred to as decision tools.
Methods The Research Ethics Board at McMaster University approved this study (project number: 12-346). The creation of the decision tools comprised the following three phases: (i) topic selection, (ii) prototype development and (iii) usability testing of tools with targeted end users.
Phase 1: Topic selection We used an electronic Delphi questionnaire to identify the three most important and relevant clinical treatment topics to be addressed by the decision tools. We circulated an invitation to participate in the Delphi survey via email to members of the Association of Canadian Haemophilia Clinic Directors (ACHCD) and patient representatives from the Canadian Haemophilia Society (CHS), who represent the targeted endusers of the tools. A few more doctors were recruited in US to reach he needed number. We valued the simplicity of having one single Delphi and not two separate for doctors and patients, and we assumed that, as the survey was circulated to educated patient representatives, they would have been knowledgeable about the evidence in the field. The research team compiled a list of seven topics, which were then sent to participants. Participants were able to add their own topics in the first round, and from these suggestions, two new topics were added in the subsequent survey. In the survey, participants were instructed to rank these topics, which were presented in random order, based on their perceptions of the importance to clinical management of haemophilia. The following three criteria were provided to participants as a guide for the ranking exercise: 1. The health treatment or screening decision should not have a single ‘best’ choice. 2. The clinical condition should be commonly encountered in haemophilia care. 3. Results of clinical research on the benefits and harms of the intervention should be available. Forced ranking ensured that each topic was assigned a unique rank. We compiled results from the first round, and generated the median score of priority and relevance for each topic. Then, we invited participants to a second round. We informed them of the median, minimum, and maximum ranks obtained by each Haemophilia (2014), 20, 800--806
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topic, and then asked them to rank each topic again according to their perceptions of its priority/relevance. We then selected the three clinical topics that obtained the highest rankings after two iterations of the second round.
Phase 2: Tool development Step 1: Systematic review. We conducted a systematic literature review for each selected topic to identify pertinent primary research studies, systematic reviews and evidence synopses for each selected topic. Step 2: Prototype development. For each topic area, the research team, comprising of an expert haematologist, a knowledge translation expert, a graphic designer, a research associate and a graduate student, created a pair of decision tools. Each prototype underwent iterative internal revision for formatting, style and content, and was produced as a downloadable and printable colour PDF. (A) Decision boxes—The format of the decision box was adapted from the decision box model (previously described [17,19]). The components of the decision box framework are listed in Box 1. Results of each systematic review were screened to identify methodologically sound studies. A haemophilia expert approved selection of studies to verify that the selected studies were relevant to clinical practice and could be used in the decision tools. After extracting quantitative and qualitative data about each outcome reported in the studies, information was categorized as either a harm or benefit of each treatment option, and the decision box framework was populated with selected information. (B) Patient decision aids—The framework for each patient decision aid was based on the Ottawa Decision Support Framework [20] and the International Patient Decision Aid Standards (IPDAS) Collaboration [21], which are both evidence-based theoretical frameworks that aim to guide the creation of effective patient decision aids. The components of the decision tools are listed in Box 1. The evidence used to build the tools was the same for the patient decision aids and the physician decision boxes. However, presentation of information differed between the tools to address the different intended audiences. For instance, presentation of information in the patient decision aids was modified to be accessible for a lay audience, by including explanations for the condition, intervention and decisions being considered, and also using language written at a grade eight reading level or less. Haemophilia (2014), 20, 800--806
Box 1. Framework the decision tools Items in both tools 1. Decision(s) to be considered 2. Intervention options 3. Scientific evidence about the benefits and harms of each option in equal detail Items differing by tool Decision boxes for physicians Patient decision aids 1. Why patient and parent/caregiver 1. Population of interest preferences matter 2. Narrative description of the 2. List of objectives of quality of evidence treatment 3. Study references 3. Value clarification and ranking
Phase 3: Usability testing: evaluation of content, format and value We interviewed target end-users of the decision tools to obtain their perceptions of the content, format, usability and value of the decision tools. Members of the research team recruited participants through their professional networks. Each interaction was audiotaped and transcribed. Members of the research team reviewed the feedback and modified the tools after each round of feedback to generate the final versions of each decision tool pair. (A) Decision boxes. Participating physicians worked in a haemophilia treatment centres, with either adult of paediatric patients with haemophilia. We completed three rounds of telephone interviews, with the first round of interviews conducted in January 2013, the second in March 2013 and the third in May and July 2013. Three physicians participated in each testing round. The decision box prototypes and an interview guide, which was based on Morville’s User Experience Model [22], were sent to each participant in advance of the interview. Prototypes were modified after each round using feedback from the interviews, and each subsequent interview round used the modified prototypes. (B) Patient decision aids. We assessed the patient decision aids in two different target groups. In May and April 2013, we conducted two focus groups with professionals working in haemophilia treatment centres in Canada. Participants were given the patient decision aid prototypes, and an interview guide in advance of the focus group meeting. Three of the nine physicians who reviewed the decision box also provided feedback regarding the content of the patient decision aids. The prototypes were revised to incorporate feedback from the professionals. In June 2013, we conducted a focus group with patients and parents © 2014 John Wiley & Sons Ltd
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of children or adults with haemophilia. Participants of this focus group were given the revised decision aid prototypes during the interview. A semi-structured interview guide was used.
2. Choosing concentrate when starting treatment in a previously untreated patient. 3. Beginning immunotolerance induction treatment in an inhibitor patient: timing and regimen.
Results
Topics 1 and 3 contained two decisions (start time and dosing), while topic 2 contained only one decision (type of factor).
Final versions of the tools can be accessed http:// hemophilia.mcmaster.ca/SDM/ and http://www. decisionbox.ulaval.ca/
Phase 1: Topic selection A total of 33 participants for the ACHD and CHS were invited to participate in the Delphi survey, of which 19(57.6%) accepted to participate. Of the topics proposed in the Delphi survey (Table 1), the following three topics were highest ranked: 1. Beginning prophylaxis treatment in a previously untreated patient: timing and regimen.
Phase 2: Prototype development The search criteria and results of each systematic review are summarized in Table 2. Literature search results were translated into draft prototypal tools before field-testing.
Phase 3: Usability testing: evaluation of content, format and value Please see Table 3 for selected statements from the decision tool testing.
Table 1. Topics present in Delphi survey and rankings. Round 1 Ranking
Round 2, iteration 1 Ranking
Round 2, iteration 2 Ranking
19 1
17 1
15 1
2
2
2
3
4
3
4
7
7
5
3
4
6 7
9 6
9 6
N/A (added after round 1) N/A (added after round 1)
8 5
8 5
Topic Number of participants in each round Beginning prophylaxis treatment in a previously untreated patient: timing and regimen Beginning immunotolerance induction treatment in an inhibitor patient: timing and regimen Choice of concentrate when starting treatment in a previously untreated patient Using secondary prophylaxis in an adult haemophilia patient Choice of concentrate when immunotolerance induction treatment in an inhibitor patient Switching concentrate in a previously treated patient Stopping immunotolerance induction treatment in a non-responding inhibitor patient Choice of prophylaxis vs. on demand therapy Continuing primary prophylaxis in a young adult with no target joint
Table 2. Systematic review search criteria and results. Topic 1
Topic 2
Primary search question
Prophylaxis treatment options for untreated children with severe haemophilia
Choosing concentrate when starting treatment in a previously untreated patient
Search headings*
Haemophilia A or B terms, factor source terms, inhibitor terms, infection terms
Search limits Databases searched
Haemophilia A or B terms, factor source terms, prophylaxis terms, factor type terms No limits MEDLINE, EMBASE
# Articles retrieved # Articles included in tools
103 21
185 18
Limited by date: 2001-2012 Cochrane Library, MEDLINE, Epidemiology Reviews
Topic 3 Immunotolerance induction for eradication of factor inhibitory antibodies in patients with congenital haemophilia A or B Haemophilia A or B terms, factor terms, inhibitor terms, immune tolerance induction terms
Limited to humans Cochrane Cystic Fibrosis and Genetic Disorders Group’s Coagulopathies Trials Register, MEDLINE, EMBASE, CINAHL 452 9
*Full search strategies for each can be found in Appendix A.
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Table 3. Selected statements from the tool testing process. Type of comment Decision boxes Impression of the tool
Impression of the tool
Recommended change
Recommended change Patient decision aids Impression of the tool
Impression of the tool Recommended change Recommended change
Selected quotation If you have two kids that are the same age that have reached the same point in the natural history of the disease, they need to be managed the same way. That happens a lot less than you would think. I think going over things with the decision boxes provides a consistent approach amongst everybody on the team. If we agree, this is how we are going to do it, and then everybody will follow that. And ultimately that really can provide better patient care. The statistics are nice. I can see having the decision box with me if I was talking to a patient about ITI. I know in my head what the numbers are, but to be able to put it out in front of you and say: Here are the numbers. Patients especially respond well to those kind of visual cues. For me, most of the information in there, I know it. But going to talk to the patient, it would be good to have a visual cue for then as I am talking, to have something where they can look and they can see the numbers, and they can see the statistics and see the pros and cons. Instead of ‘low’ risk of inhibitors in plasma-derived factor VIII, I would say ‘Lower’ risk because when most people talk about it, they’re almost always comparing it as lower than recombinant. The argument is that the risk is slightly lower than recombinant, not necessarily that it’s a low risk. Specific that it is specifically ‘target’ bleeds and not just bleeds. For me, if I had this decision aid, it would stimulate questions. I was the one who took the boys to the clinic because my husband was working. We were very involved, so it would have been great to go through this document with my husband. We were always on the same page but it would help. So if I had this, then I would take it and go to clinic and it would really keep me focussed on what my questions would be. I like the word “Risks”. That is just what they are – risks. Instead of using ‘no X’ for not at all, use a ‘0’ or something that way you know they just haven’t skipped over it. Why not just say ‘more injections on a regular basis rather than just for bleeding episodes’ instead of increased treatment burden.
(A) Decision boxes. Of the physicians who tested the decision boxes, five were male and six worked in paediatric haemophilia clinics. Six practiced in Canada and three practiced in the United States of America. The mean age of participants was 45 years (range: 31–71) and average length of time caring for haemophilia patients was 15 years (range: 2–40). Overall, physicians’ perceptions of the decision boxes were positive, and the overall concept and purpose of using decision tools was well received. Participants appreciated the structure of the decision boxes, which provided, ‘a framework for how to think about a problem in a systematic way’. While most physicians were unfamiliar with decision tools, there was overall agreement that such tools would be useful both before and during a clinical encounter with a patient. Physicians provided useable feedback about how to improve the tools. Many felt that the documents were quite ‘busy’ but agreed that the information contained was necessary. (B) Patient decision aids. A member of the research team (AB) with experience in qualitative analysis ran the focus groups. Of the initial two focus groups, participants included four haemophilia nurse coordinators, one social worker and one physiotherapist. Four worked in Ontario and one worked in British Columbia. All participants were female and the mean age was 46 years (range: 30–60) and the average length of time working in a haemophilia clinic was 16 years (range: 1–45). The final focus group consisted of a mother and father of a one-year-old boy with haemophilia A, a Haemophilia (2014), 20, 800--806
mother of two adults with haemophilia A, and an adult male with haemophilia A. Similar to the decision boxes, the patient decision aids were well received, and participants claimed that the tool would have been useful during initial encounters with a physician. The decision aids were described as ‘easy to read’. Based on user feedback changes were made to the text, method of data presentation (e.g. use of text blocks or tables), and graphics and logos of the tools.
Discussion and conclusion Decision tools are interventions that are used to help individuals make informed decisions and to facilitate shared decision-making [13]. This article outlines a successful method for developing and user-testing three novel, evidence-based, two-sided decision tools for treatment decisions in haemophilia; thus, showing that it is feasible to develop decision tools in a rare disease field. To our knowledge, there are no evidence-based decision tools to facilitate shared decision-making for treatments in the field of haemophilia. Further, these tools are unique in that they are two-sided, and are meant to be used by both the physician and patient. Creating decision tools for a rare disorder, such as haemophilia, has many challenges that are not present when developing similar tools for more prevalent diseases. According to the hierarchy of evidence, systematic reviews of randomized trials followed by individual randomized control trials constitute the highest levels of evidence [23]. In haemophilia, where there have been fewer than 20 randomized control © 2014 John Wiley & Sons Ltd
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trials conducted, and similarly low numbers of systematic literature reviews with quantitative data syntheses, it is often difficult to obtain research for what typically qualifies as ‘best evidence’ in other fields of medicine [24,25], where the majority of evidence does come from the highest levels of evidence. Because of this, the selection process of evidence to be used for a decision tool in a rare disease area is less straightforward and may rely on other factors, such as expert opinion, as compared to more prevalent diseases. For the most part, the format of the decision boxes described in this article followed the format of the decision boxes as formally proposed by Giguere et al. [17]. However, we did not use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to formally evaluate research data. Given that studies referenced in the haemophilia decision tools used observational methods, had small sample sizes and reported few events, the quality of this evidence would likely be characterized as ‘low’ or ‘very low’ using the GRADE approach [26], which we thought was not functional and perhaps misleading. Instead, we narratively described the confidence in our results, and gave reasoning for each judgement. However, the GRADE method is currently being tested for use with evidence for rare diseases. In subsequent updates of the tools, we may use the GRADE approach to evaluate the evidence (the article on GRADE application to rare diseases has been recently submitted). Overall, our usability testing, although limited in sample size and scope, indicated that the tools were viewed positively by targeted end-users. While we did not intend to conduct a qualitative analysis, our results provide compelling anecdotal evidence that decision tools, such as the ones described in this article, are useful to both patients and physicians alike. A limitation of our study existed in how the usability testing was carried out. The tools are intended to be complementary, and used simultaneously in a clinical encounter. However, we only completed independent user testing in our target populations. This did not allow us to see how the tools would be used in a realistic setting, and we were not able to gather information about how these tools would work together and the necessity of both tools. As well, we used a purposive, convenience sample to test our tools. Given that participation was voluntary, it is possible that study participants were more likely to take a more active role in acquiring information about haemophilia management compared to a more representative sample, and hence the very positive perceptions of the tools may be an overestimation of the actual perception. Further, due to feasibility constraints, participation of patients and
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patient representatives in the tool development and finalization process was lower than that of health care providers. As a consequence, some patient perspectives may have not been captured. We are open to further refinement of the tools through improvement derived by suggestions generated during real practice usage. Nonetheless, the results of this study not only show that creating decision tools in a rare disease field such as haemophilia is feasible, but also that such tools are positively received and may be beneficial in clinical practice. However, concrete evidence of their efficacy and usefulness needs to be established before the use of these tools can be widely advocated. To address this, future directions for this project include conducting a cluster, randomized trial to assess practical value and impact on clinical practice, including communication, satisfaction, patient understanding and adherence. Another future avenue will be to develop interactive online versions of the decision tools, where end-users will be able to personalize the content of the decision tools.
Acknowledgements We are grateful to all of the patients, patients’ caregivers, and colleagues, who took part in the interviews and focus groups. We are indebted to Ms. Emma Iserman for supporting the final production of the decision tools.
Funding sources Biogen Idec, MITACS Accelerate Canada.
Role of funding source Biogen Idec provided unrestricted economic support for the literature search, interviews and focus group-related expenses and study coordination. Biogen Idec and MITACS supported a 4-month internship for A.A for literature review and design activities. None of the funders provided input to the content of the decision tools.
Disclosures A. Athale, A. Giguere, A. Barbara have no conflicts of interest to declare. S. Krassova is a former employee of Biogen Idec. A. Iorio received honoraria from Biogen Idec, Bayer, Baxter and Novo Nordisk for giving educational talks, sitting on scientific advisory boards and consulting on scientific projects. As well, A. Iorio has received research support from the same organizations.
Authorship roles Project conception and protocol draft: A Giguere, A. Barbara, S. Krassova and A. Iorio; Development of tool prototypes: A. Athale, A. Barbara, A. Giguere and A. Iorio; Conducting interviews: A. Barbara; Drafting of manuscript: A. Athale; Consolidation of manuscript: A. Athale, A. Barbara, A. Giguere, S. Krassova and A. Iorio.
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11 Zwolsman S, te Pas E, Hooft L, Wieringade Waard M, and van Dijk N. Barriers to GPs’ use of evidence-based medicine: a systematic review. Br J Gen Pract 2012; 62: e511–21. 12 Charles C, Gafni A, Whelan T. Decisionmaking in the physician-patient encounter: revisiting the shared treatment decisionmaking model. Soc Sci Med 1999; 49: 651–61. 13 Stacey D, Bennett CL, Barry MJ et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev 2011; 10: CD001431. 14 Evans R, Edwards A, Brett J et al. Reduction in uptake of PSA tests following decision aids: systematic review of current aids and their evaluations. Patient Educ Couns 2005; 58: 13–26. 15 Hack TF, Degner LF, Watson P, Sinha L. Do patients benefit from participating in medical decision making? Longitudinal follow-up of women with breast cancer. Psychooncology 2006; 15: 9–19. 16 Merenstein D, Diener-West M, Krist A, Pinneger M, Cooper LA. An assessment of the shared-decision model in parents of children with acute otitis media. Pediatrics 2005; 116: 1267–75. 17 Giguere A, Legare F, Grad R et al. Developing and user-testing Decision boxes to facilitate shared decision making in primary care–a study protocol. BMC Med Inform Decis Mak 2011; 11: 17. 18 Mullan RJ, Montori VM, Shah ND et al. The diabetes mellitus medication choice decision aid: a randomized trial. Arch Intern Med 2009; 169: 1560–8. 19 Giguere A, Legare F, Grad R et al. Decision boxes for clinicians to support evidence-based practice and shared decision making: the user experience. Implement Sci 2012; 7: 72. 20 Ottawa Hospital Research Institute. Ottawa Decision Support Frameworks.
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[Online]. Available: http://decisionaid.ohri. ca/odsf.html. Elwyn G, O’Connor A, Stacey D et al., “International Patient Decision Aids Standards (IPDAS) Collaboration. Developing a quality criteria framework for patient decision aid: online international Delphi consensus process,” Br Med J 2006; 333: 417– 22. Elwyn G, O’Connor A, Stacey D, Volk R, Edwards A, Coulter A, … Whelan, T. . Developing a quality criteria framework for patient decision aids: online international Delphi consensus process. BMJ (Clinical Research Ed.) 2006; 333(7565): 417–22. doi:10.1136/bmj.38926.629329.AE. Moreville P, “Morville’s User Experience Design.” [Online]. Available: http://semanticstudios.com/publications/semantics/ 000029.php. Guyatt GH. Users’ Guides to the Medical Literature. JAMA 1995; 274: 1800. Iorio A, Marcucci M, Makris M. Concentrate-related inhibitor risk: is a difference always real? J Thromb Haemost 2011; 9: 2176–9. Behera M, Kumar A, Soares HP, Sokol L, Djulbegovic B. Evidence-based medicine for rare diseases: implications for data interpretation and clinical trial design. Cancer Control 2007; 14: 160–6. Guyatt GH, Oxman AD, Vist GE et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336: 924–6.
Supporting Information Additional Supporting Information may be found in the online version of this article: Appendix S1. Search Strategies. Appendix S2. Decision Boxes for Physicians and Patient Decision Aids.
© 2014 John Wiley & Sons Ltd
DOI: 10.1111/hae.12495
ORIGINAL ARTICLE Clinical haemophilia
Developing a two-sided intervention to facilitate shared decision-making in haemophilia: decision boxes for clinicians and patient decision aids for patients A . A T H A L E , * A . G I G U E R E , † A . B A R B A R A , * S . K R A S S O V A ‡ and A . I O R I O * § *Department of Clinical Epidemiology and Biostatistics, Health Information Research Unit, McMaster University, Hamilton, Ontario, Canada; †Department of Family Medicine and Emergency Medicine, Office of Education and Continuing Professional Development, Laval University, Quebec, Canada; ‡ Medical Director,, Zurich, Switzerland; and §Hemophilia Treatment Center, McMaster University, Hamilton, Ontario, Canada
Background. People with haemophilia face many treatment decisions, which are largely informed by evidence from observational studies. Without evidence-based ‘best’ treatment options, patient preferences play a large role in decisions regarding therapy. The shared decision-making (SDM) process allows patients and health care providers to make decisions collaboratively based on available evidence, and patient preferences. Decision tools can help the SDM process. The objective of this project was to develop two-sided decision tools, decision boxes for physicians and patient decision aids for patients, to facilitate SDM for treatment decisions in haemophilia. Methods. Development of the decision tools comprised three phases: topic selection, prototype development and usability testing with targeted end-users. Topics were selected using a Delphi survey. Tool prototypes were based on a previously validated framework and were informed by systematic literature reviews. Patients, through focus groups, and physicians,
through interviews, reviewed the prototypes iteratively for comprehensibility and usability. Results. The chosen topics were: (i) prophylactic treatment: when to start and dosing, (ii) choosing factor source and (iii) immunotolerance induction: when to start and dosing. Intended end users (both health care providers and haemophilia patients and caregivers) were engaged in the development process. Overall perception of the decision tools was positive, and the purpose of using the tools was well received. Conclusions. This study demonstrates the feasibility of developing decision tools for haemophilia treatment decisions. It also provides anecdotal evidence of positive perceptions of such tools. Future directions include assessment of the tools’ practical value and impact on clinical practice.
Background
haemophilia B [2]. Without intervention, haemophilia manifests itself in recurrent bleeding in joints and muscles, joint arthropathy, and susceptibility to uncontrolled bleeding after external trauma [3]. While there is currently no proven cure, symptoms of haemophilia can be effectively treated with factor replacement therapy using recombinant or plasma-derived FVIII or FIX. Factor concentrates can be infused after a bleeding episode has occurred (on-demand treatment) or to prevent bleeding incidents (prophylaxis treatment)[4,5]. Development of factor inhibitory antibodies, which occurs in 20–50% of previously untreated patients, is a significant complication of haemophilia treatment, because the presence of an inhibitor renders exogenous factor concentrate ineffective [6]. To date, immunotolerance induction is the prefer-
Congenital haemophilia is a rare, genetically transmitted disorder that is characterized by reduced levels of clotting factor VIII (FVIII) in haemophilia A or factor IX (FIX) in haemophilia B [1]. Haemophilia severity is classified by baseline levels of FVIII or FIX. Disease prevalence is estimated at about 1:10 000 cases for severe haemophilia A and a much lower prevalence of Correspondence: Dr. Alfonso Iorio, HiRU, CRL-140, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. Tel.: 905 525 9140 ext 22421; fax: +1 905-526-8447; e-mail: [email protected] Accepted after revision 09 June 2014 800
Keywords: congenital haemophilia, decision aids, intervention, shared decision-making
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ential treatment to eradicate inhibitors in people with haemophilia [7]. Being a rare, chronic disease, research in haemophilia is challenging [8]. Feasibility concerns, such as adequate recruitment and long follow-up times, and methodological challenges, such as difficulty in blinding and unavailability of objective, surrogate outcomes, constitute hurdles in conducting research. Resultantly, there are relatively few randomized clinical trials completed in haemophilia research, and much of the current evidence of the effectiveness of haemophilia treatment options comes from observational, often retrospective, studies, uncontrolled case series, or national and international registries [8,9]. Current research has identified several efficacious treatments options for treatment decisions in haemophilia, such as ideal dosing regimens and starting times of therapy [7,10]. However, without evidencebased indications to unequivocally identify a superior treatment option, uncertainty exists when choosing treatment regimens for patients with haemophilia, and patient preferences play a larger role in the decisionmaking process [11]. Shared decision-making (SDM) is a promising avenue for applying scientific evidence to clinical practice. SDM is a model that helps clinicians and patients make joint health care decisions based on (i) the best available evidence of benefits and harms of treatment options and (ii) patients’ values and preferences in regard to the treatment options [12]. In other clinical fields [13], SDM has been shown to increase the use of the treatment option that is most clearly associated with health benefits [14]. Its use has been associated with a higher quality of life and increased patient satisfaction [15,16]. The SDM process is useful when there are numerous options for a treatment decision, as is often the case in haemophilia. While awaiting formal testing to assess the effects of SDM on clinical outcomes, one can conjecture, based on a purely theoretical basis, that application of the SDM framework to a clinical encounter in haemophilia may improve communication between patients and health care providers and further encourage active participation from both parties in the decision-making process. Decision aids are interventions that help facilitate SDM, and have been used in other clinical areas [13]. While most decision aids are designed for either the patient [13] or physician [17], some decision aid interventions are designed for contemporaneous use by both the clinician and patient [18]. The objective of this project was to create decision tools to inform and facilitate decision-making about treatment options in grey areas of haemophilia management. The decision tool model we have used consists of two tools for each clinical decision– a decision box for physicians and a corresponding patient deci© 2014 John Wiley & Sons Ltd
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sion aid. These tools are intended for use by clinicians and their patients to prepare both parties for a clinical encounter, and are meant to help both parties make joint, informed, value-based decisions about haemophilia treatment. The decision box for physicians and decision aid for patients will be collectively referred to as decision tools.
Methods The Research Ethics Board at McMaster University approved this study (project number: 12-346). The creation of the decision tools comprised the following three phases: (i) topic selection, (ii) prototype development and (iii) usability testing of tools with targeted end users.
Phase 1: Topic selection We used an electronic Delphi questionnaire to identify the three most important and relevant clinical treatment topics to be addressed by the decision tools. We circulated an invitation to participate in the Delphi survey via email to members of the Association of Canadian Haemophilia Clinic Directors (ACHCD) and patient representatives from the Canadian Haemophilia Society (CHS), who represent the targeted endusers of the tools. A few more doctors were recruited in US to reach he needed number. We valued the simplicity of having one single Delphi and not two separate for doctors and patients, and we assumed that, as the survey was circulated to educated patient representatives, they would have been knowledgeable about the evidence in the field. The research team compiled a list of seven topics, which were then sent to participants. Participants were able to add their own topics in the first round, and from these suggestions, two new topics were added in the subsequent survey. In the survey, participants were instructed to rank these topics, which were presented in random order, based on their perceptions of the importance to clinical management of haemophilia. The following three criteria were provided to participants as a guide for the ranking exercise: 1. The health treatment or screening decision should not have a single ‘best’ choice. 2. The clinical condition should be commonly encountered in haemophilia care. 3. Results of clinical research on the benefits and harms of the intervention should be available. Forced ranking ensured that each topic was assigned a unique rank. We compiled results from the first round, and generated the median score of priority and relevance for each topic. Then, we invited participants to a second round. We informed them of the median, minimum, and maximum ranks obtained by each Haemophilia (2014), 20, 800--806
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topic, and then asked them to rank each topic again according to their perceptions of its priority/relevance. We then selected the three clinical topics that obtained the highest rankings after two iterations of the second round.
Phase 2: Tool development Step 1: Systematic review. We conducted a systematic literature review for each selected topic to identify pertinent primary research studies, systematic reviews and evidence synopses for each selected topic. Step 2: Prototype development. For each topic area, the research team, comprising of an expert haematologist, a knowledge translation expert, a graphic designer, a research associate and a graduate student, created a pair of decision tools. Each prototype underwent iterative internal revision for formatting, style and content, and was produced as a downloadable and printable colour PDF. (A) Decision boxes—The format of the decision box was adapted from the decision box model (previously described [17,19]). The components of the decision box framework are listed in Box 1. Results of each systematic review were screened to identify methodologically sound studies. A haemophilia expert approved selection of studies to verify that the selected studies were relevant to clinical practice and could be used in the decision tools. After extracting quantitative and qualitative data about each outcome reported in the studies, information was categorized as either a harm or benefit of each treatment option, and the decision box framework was populated with selected information. (B) Patient decision aids—The framework for each patient decision aid was based on the Ottawa Decision Support Framework [20] and the International Patient Decision Aid Standards (IPDAS) Collaboration [21], which are both evidence-based theoretical frameworks that aim to guide the creation of effective patient decision aids. The components of the decision tools are listed in Box 1. The evidence used to build the tools was the same for the patient decision aids and the physician decision boxes. However, presentation of information differed between the tools to address the different intended audiences. For instance, presentation of information in the patient decision aids was modified to be accessible for a lay audience, by including explanations for the condition, intervention and decisions being considered, and also using language written at a grade eight reading level or less. Haemophilia (2014), 20, 800--806
Box 1. Framework the decision tools Items in both tools 1. Decision(s) to be considered 2. Intervention options 3. Scientific evidence about the benefits and harms of each option in equal detail Items differing by tool Decision boxes for physicians Patient decision aids 1. Why patient and parent/caregiver 1. Population of interest preferences matter 2. Narrative description of the 2. List of objectives of quality of evidence treatment 3. Study references 3. Value clarification and ranking
Phase 3: Usability testing: evaluation of content, format and value We interviewed target end-users of the decision tools to obtain their perceptions of the content, format, usability and value of the decision tools. Members of the research team recruited participants through their professional networks. Each interaction was audiotaped and transcribed. Members of the research team reviewed the feedback and modified the tools after each round of feedback to generate the final versions of each decision tool pair. (A) Decision boxes. Participating physicians worked in a haemophilia treatment centres, with either adult of paediatric patients with haemophilia. We completed three rounds of telephone interviews, with the first round of interviews conducted in January 2013, the second in March 2013 and the third in May and July 2013. Three physicians participated in each testing round. The decision box prototypes and an interview guide, which was based on Morville’s User Experience Model [22], were sent to each participant in advance of the interview. Prototypes were modified after each round using feedback from the interviews, and each subsequent interview round used the modified prototypes. (B) Patient decision aids. We assessed the patient decision aids in two different target groups. In May and April 2013, we conducted two focus groups with professionals working in haemophilia treatment centres in Canada. Participants were given the patient decision aid prototypes, and an interview guide in advance of the focus group meeting. Three of the nine physicians who reviewed the decision box also provided feedback regarding the content of the patient decision aids. The prototypes were revised to incorporate feedback from the professionals. In June 2013, we conducted a focus group with patients and parents © 2014 John Wiley & Sons Ltd
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of children or adults with haemophilia. Participants of this focus group were given the revised decision aid prototypes during the interview. A semi-structured interview guide was used.
2. Choosing concentrate when starting treatment in a previously untreated patient. 3. Beginning immunotolerance induction treatment in an inhibitor patient: timing and regimen.
Results
Topics 1 and 3 contained two decisions (start time and dosing), while topic 2 contained only one decision (type of factor).
Final versions of the tools can be accessed http:// hemophilia.mcmaster.ca/SDM/ and http://www. decisionbox.ulaval.ca/
Phase 1: Topic selection A total of 33 participants for the ACHD and CHS were invited to participate in the Delphi survey, of which 19(57.6%) accepted to participate. Of the topics proposed in the Delphi survey (Table 1), the following three topics were highest ranked: 1. Beginning prophylaxis treatment in a previously untreated patient: timing and regimen.
Phase 2: Prototype development The search criteria and results of each systematic review are summarized in Table 2. Literature search results were translated into draft prototypal tools before field-testing.
Phase 3: Usability testing: evaluation of content, format and value Please see Table 3 for selected statements from the decision tool testing.
Table 1. Topics present in Delphi survey and rankings. Round 1 Ranking
Round 2, iteration 1 Ranking
Round 2, iteration 2 Ranking
19 1
17 1
15 1
2
2
2
3
4
3
4
7
7
5
3
4
6 7
9 6
9 6
N/A (added after round 1) N/A (added after round 1)
8 5
8 5
Topic Number of participants in each round Beginning prophylaxis treatment in a previously untreated patient: timing and regimen Beginning immunotolerance induction treatment in an inhibitor patient: timing and regimen Choice of concentrate when starting treatment in a previously untreated patient Using secondary prophylaxis in an adult haemophilia patient Choice of concentrate when immunotolerance induction treatment in an inhibitor patient Switching concentrate in a previously treated patient Stopping immunotolerance induction treatment in a non-responding inhibitor patient Choice of prophylaxis vs. on demand therapy Continuing primary prophylaxis in a young adult with no target joint
Table 2. Systematic review search criteria and results. Topic 1
Topic 2
Primary search question
Prophylaxis treatment options for untreated children with severe haemophilia
Choosing concentrate when starting treatment in a previously untreated patient
Search headings*
Haemophilia A or B terms, factor source terms, inhibitor terms, infection terms
Search limits Databases searched
Haemophilia A or B terms, factor source terms, prophylaxis terms, factor type terms No limits MEDLINE, EMBASE
# Articles retrieved # Articles included in tools
103 21
185 18
Limited by date: 2001-2012 Cochrane Library, MEDLINE, Epidemiology Reviews
Topic 3 Immunotolerance induction for eradication of factor inhibitory antibodies in patients with congenital haemophilia A or B Haemophilia A or B terms, factor terms, inhibitor terms, immune tolerance induction terms
Limited to humans Cochrane Cystic Fibrosis and Genetic Disorders Group’s Coagulopathies Trials Register, MEDLINE, EMBASE, CINAHL 452 9
*Full search strategies for each can be found in Appendix A.
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Table 3. Selected statements from the tool testing process. Type of comment Decision boxes Impression of the tool
Impression of the tool
Recommended change
Recommended change Patient decision aids Impression of the tool
Impression of the tool Recommended change Recommended change
Selected quotation If you have two kids that are the same age that have reached the same point in the natural history of the disease, they need to be managed the same way. That happens a lot less than you would think. I think going over things with the decision boxes provides a consistent approach amongst everybody on the team. If we agree, this is how we are going to do it, and then everybody will follow that. And ultimately that really can provide better patient care. The statistics are nice. I can see having the decision box with me if I was talking to a patient about ITI. I know in my head what the numbers are, but to be able to put it out in front of you and say: Here are the numbers. Patients especially respond well to those kind of visual cues. For me, most of the information in there, I know it. But going to talk to the patient, it would be good to have a visual cue for then as I am talking, to have something where they can look and they can see the numbers, and they can see the statistics and see the pros and cons. Instead of ‘low’ risk of inhibitors in plasma-derived factor VIII, I would say ‘Lower’ risk because when most people talk about it, they’re almost always comparing it as lower than recombinant. The argument is that the risk is slightly lower than recombinant, not necessarily that it’s a low risk. Specific that it is specifically ‘target’ bleeds and not just bleeds. For me, if I had this decision aid, it would stimulate questions. I was the one who took the boys to the clinic because my husband was working. We were very involved, so it would have been great to go through this document with my husband. We were always on the same page but it would help. So if I had this, then I would take it and go to clinic and it would really keep me focussed on what my questions would be. I like the word “Risks”. That is just what they are – risks. Instead of using ‘no X’ for not at all, use a ‘0’ or something that way you know they just haven’t skipped over it. Why not just say ‘more injections on a regular basis rather than just for bleeding episodes’ instead of increased treatment burden.
(A) Decision boxes. Of the physicians who tested the decision boxes, five were male and six worked in paediatric haemophilia clinics. Six practiced in Canada and three practiced in the United States of America. The mean age of participants was 45 years (range: 31–71) and average length of time caring for haemophilia patients was 15 years (range: 2–40). Overall, physicians’ perceptions of the decision boxes were positive, and the overall concept and purpose of using decision tools was well received. Participants appreciated the structure of the decision boxes, which provided, ‘a framework for how to think about a problem in a systematic way’. While most physicians were unfamiliar with decision tools, there was overall agreement that such tools would be useful both before and during a clinical encounter with a patient. Physicians provided useable feedback about how to improve the tools. Many felt that the documents were quite ‘busy’ but agreed that the information contained was necessary. (B) Patient decision aids. A member of the research team (AB) with experience in qualitative analysis ran the focus groups. Of the initial two focus groups, participants included four haemophilia nurse coordinators, one social worker and one physiotherapist. Four worked in Ontario and one worked in British Columbia. All participants were female and the mean age was 46 years (range: 30–60) and the average length of time working in a haemophilia clinic was 16 years (range: 1–45). The final focus group consisted of a mother and father of a one-year-old boy with haemophilia A, a Haemophilia (2014), 20, 800--806
mother of two adults with haemophilia A, and an adult male with haemophilia A. Similar to the decision boxes, the patient decision aids were well received, and participants claimed that the tool would have been useful during initial encounters with a physician. The decision aids were described as ‘easy to read’. Based on user feedback changes were made to the text, method of data presentation (e.g. use of text blocks or tables), and graphics and logos of the tools.
Discussion and conclusion Decision tools are interventions that are used to help individuals make informed decisions and to facilitate shared decision-making [13]. This article outlines a successful method for developing and user-testing three novel, evidence-based, two-sided decision tools for treatment decisions in haemophilia; thus, showing that it is feasible to develop decision tools in a rare disease field. To our knowledge, there are no evidence-based decision tools to facilitate shared decision-making for treatments in the field of haemophilia. Further, these tools are unique in that they are two-sided, and are meant to be used by both the physician and patient. Creating decision tools for a rare disorder, such as haemophilia, has many challenges that are not present when developing similar tools for more prevalent diseases. According to the hierarchy of evidence, systematic reviews of randomized trials followed by individual randomized control trials constitute the highest levels of evidence [23]. In haemophilia, where there have been fewer than 20 randomized control © 2014 John Wiley & Sons Ltd
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trials conducted, and similarly low numbers of systematic literature reviews with quantitative data syntheses, it is often difficult to obtain research for what typically qualifies as ‘best evidence’ in other fields of medicine [24,25], where the majority of evidence does come from the highest levels of evidence. Because of this, the selection process of evidence to be used for a decision tool in a rare disease area is less straightforward and may rely on other factors, such as expert opinion, as compared to more prevalent diseases. For the most part, the format of the decision boxes described in this article followed the format of the decision boxes as formally proposed by Giguere et al. [17]. However, we did not use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to formally evaluate research data. Given that studies referenced in the haemophilia decision tools used observational methods, had small sample sizes and reported few events, the quality of this evidence would likely be characterized as ‘low’ or ‘very low’ using the GRADE approach [26], which we thought was not functional and perhaps misleading. Instead, we narratively described the confidence in our results, and gave reasoning for each judgement. However, the GRADE method is currently being tested for use with evidence for rare diseases. In subsequent updates of the tools, we may use the GRADE approach to evaluate the evidence (the article on GRADE application to rare diseases has been recently submitted). Overall, our usability testing, although limited in sample size and scope, indicated that the tools were viewed positively by targeted end-users. While we did not intend to conduct a qualitative analysis, our results provide compelling anecdotal evidence that decision tools, such as the ones described in this article, are useful to both patients and physicians alike. A limitation of our study existed in how the usability testing was carried out. The tools are intended to be complementary, and used simultaneously in a clinical encounter. However, we only completed independent user testing in our target populations. This did not allow us to see how the tools would be used in a realistic setting, and we were not able to gather information about how these tools would work together and the necessity of both tools. As well, we used a purposive, convenience sample to test our tools. Given that participation was voluntary, it is possible that study participants were more likely to take a more active role in acquiring information about haemophilia management compared to a more representative sample, and hence the very positive perceptions of the tools may be an overestimation of the actual perception. Further, due to feasibility constraints, participation of patients and
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patient representatives in the tool development and finalization process was lower than that of health care providers. As a consequence, some patient perspectives may have not been captured. We are open to further refinement of the tools through improvement derived by suggestions generated during real practice usage. Nonetheless, the results of this study not only show that creating decision tools in a rare disease field such as haemophilia is feasible, but also that such tools are positively received and may be beneficial in clinical practice. However, concrete evidence of their efficacy and usefulness needs to be established before the use of these tools can be widely advocated. To address this, future directions for this project include conducting a cluster, randomized trial to assess practical value and impact on clinical practice, including communication, satisfaction, patient understanding and adherence. Another future avenue will be to develop interactive online versions of the decision tools, where end-users will be able to personalize the content of the decision tools.
Acknowledgements We are grateful to all of the patients, patients’ caregivers, and colleagues, who took part in the interviews and focus groups. We are indebted to Ms. Emma Iserman for supporting the final production of the decision tools.
Funding sources Biogen Idec, MITACS Accelerate Canada.
Role of funding source Biogen Idec provided unrestricted economic support for the literature search, interviews and focus group-related expenses and study coordination. Biogen Idec and MITACS supported a 4-month internship for A.A for literature review and design activities. None of the funders provided input to the content of the decision tools.
Disclosures A. Athale, A. Giguere, A. Barbara have no conflicts of interest to declare. S. Krassova is a former employee of Biogen Idec. A. Iorio received honoraria from Biogen Idec, Bayer, Baxter and Novo Nordisk for giving educational talks, sitting on scientific advisory boards and consulting on scientific projects. As well, A. Iorio has received research support from the same organizations.
Authorship roles Project conception and protocol draft: A Giguere, A. Barbara, S. Krassova and A. Iorio; Development of tool prototypes: A. Athale, A. Barbara, A. Giguere and A. Iorio; Conducting interviews: A. Barbara; Drafting of manuscript: A. Athale; Consolidation of manuscript: A. Athale, A. Barbara, A. Giguere, S. Krassova and A. Iorio.
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Supporting Information Additional Supporting Information may be found in the online version of this article: Appendix S1. Search Strategies. Appendix S2. Decision Boxes for Physicians and Patient Decision Aids.
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