Support Care Cancer DOI 10.1007/s00520-014-2559-7
ORIGINAL ARTICLE
Development of clinical practice guidelines for supportive care in childhood cancer—prioritization of topics using a Delphi approach E. A. H. Loeffen & R. L. Mulder & L. C. M. Kremer & E. M. C. Michiels & F. C. H. Abbink & L. M. Ball & H. Segers & A. M. C. Mavinkurve-Groothuis & F. J. Smit & I. J. M. Vonk & M. D. vd Wetering & W. J. E. Tissing
Received: 22 August 2014 / Accepted: 7 December 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Introduction Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert Electronic supplementary material The online version of this article (doi:10.1007/s00520-014-2559-7) contains supplementary material, which is available to authorized users. E. A. H. Loeffen : W. J. E. Tissing (*) Department of Pediatric Oncology/Hematology, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands e-mail: [email protected] R. L. Mulder : L. C. M. Kremer : M. D. vd Wetering Department of Pediatric Oncology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands E. M. C. Michiels : I. J. M. Vonk Department of Pediatric Oncology/Hematology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands F. C. H. Abbink Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands L. M. Ball Department of Pediatrics, Stem Cell Transplantation Unit, Leiden University Medical Center, Leiden, The Netherlands H. Segers Department of Hematology and Oncology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands A. M. C. Mavinkurve-Groothuis Department of Pediatric Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands F. J. Smit Department of Pediatrics, Maasstad Hospital, Rotterdam, The Netherlands
opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed with a well-defined methodology and include a systematic search of literature, evidence summaries, and a transparent description of the decision process for the final recommendations. Development of CPGs is time consuming; therefore, it is important to prioritize topics for which there is the greatest clinical demand. Objectives This study aims to prioritize childhood cancer supportive care topics for development of CPGs. Methods A Delphi survey consisting of two rounds was conducted to prioritize relevant childhood cancer supportive care topics for the development of CPGs. A group of experts comprising 15 pediatric oncologists, 15 pediatric oncology nurses, and 15 general pediatricians involved in care for childhood cancer patients were invited to participate. All relevant supportive care topics in childhood cancer were rated. Results In both rounds, 36 panellists (82 %) responded. Agreement between panellists was very good, with an intraclass correlation coefficient of 0.918 (95 % confidence interval (CI)=0.849–0.966, p2.5 on all three questions in round 1 were selected. This was chosen because we wanted to start supportive care guideline development with topics that are clinically most relevant, which we regarded as occurring often, being relatively severe, and having adequate treatment options. Of these, the 20 highest scoring topics were selected and presented in descending order in the second Delphi round
(see electronic supplementary material appendix II). This was limited to the 20 highest scoring items as we wanted our questionnaires to be focused on the most important topics to start CPG development with and minimize the risk of causing fatigue (and thus perhaps non-response) in our panellists. Also, all written additions were included. In this second round, the panellists were asked to rate how important it is that a CPG will be developed for the specific topic, on a 5point Likert scale ranging from 1 (unimportant) to 5 (very important). Before commencing our survey, the core research group decided to initially limit the number of rounds to two, as this Delphi survey had a prioritizing rather than a selective character. We decided to consider more rounds when there was no agreement between panellists. Each questionnaire took less than 15 min to complete. Analysis We explored agreement between panellists. We determined there was agreement when more than 66 % of all panellists rated a 4 or 5 on the 5-point Likert scale of a specific topic. In addition, the level of agreement between panellists was estimated with the intraclass correlation coefficient (ICC), set to a two-way mixed model with absolute agreement [20]. As our
Formation of core research group, compilation of list with relevant topics for supportive care in childhood cancer
Inivitation of expert panellists
45 invited 44 agreed to participate / 1 non-responder
41 supportive care topics Rate on 5-point Likert scale: - Prevalence
ROUND 1
5. frequently / 4. occasionally / 3. rarely / 2. very rarely / 1. Never
-
Severity 5. extremely / 4. very / 3. moderately / 2. slightly / 1. not (severe)
- Adequate treatment options 5. a great deal / 4. many / 3. somewhat / 2. little / 1. none
Number of respondents: 36/44 (82%) 10 written additions 21 topics excluded from round 2: - 16 topics: no mean >2.5 on all 3 questions - 5 topics: not top 20
ROUND 2
30 supportive care topics Rate on 5-point Likert scale: How important is it that a CPG will be developed for this specific topic? 5. very important / 4. important / 3. moderately important / 2. of little importance / 1. unimportant
Number of respondents: 36/44 (82%) 5 non-responders that did respond in round 1 5 additional experts that did not respond in round 1
Prioritization of childhood cancer supportive care topics for the development of clinical practice guidelines Fig. 1 Outline of the Delphi approach
Support Care Cancer Table 1
Results of the Delphi survey round 1, sorted by descending overall mean score on all 3 items
Supportive care topic
Mean scorea Prevalence
Severity
Adequate treatment options
Overall mean score
Anemiab Infectionb Nausea/vomitingb Thrombocytopeniab Painb Febrile neutropeniab Constipationb Sepsisb Malnutritionb Leukopeniab Psychosocial issuesb Tumor lysis syndrome Palliative careb Hypertensionb
4.50 4.28 4.69 4.56 4.06 4.06 4.00 2.78 3.81 4.67 4.06 2.41 2.81 3.00
2.89 3.78 3.25 3.03 3.72 3.44 2.92 4.67 3.22 3.69 3.60 3.79 4.03 3.03
4.72 4.02 4.02 4.33 4.06 3.83 4.42 3.72 4.00 2.42 3.00 4.15 3.52 4.22
4.04 4.03 3.99 3.97 3.94 3.78 3.78 3.72 3.68 3.59 3.55 3.45 3.45 3.42
Mucositis (oral) b Graft versus host disease after HSCTb Virus reactivation after HSCTb Varicella virusb Terminal careb Mucositis (gastrointestinal) b Endocrine complicationsb PAC/VAP; occlusion Thrombosis Menstruation Sub-/infertility Fatigue Sinus thrombosis Diabetes mellitus Pancreatitis Neutropenic colitis Nephrological complications; tubular Hyperviscosity syndrome
3.69 3.00 3.04 2.78 2.64 3.25 2.68 2.83 2.31 3.06 3.19 4.11 1.94 2.17 2.00 2.00 2.64 1.43
3.47 4.15 4.04 3.47 4.09 3.69 3.33 3.23 3.80 2.56 4.36 3.17 4.17 3.34 4.25 4.06 3.21 3.47
3.00 3.00 3.04 3.77 3.27 2.92 3.68 3.60 3.51 3.94 2.03 2.28 3.43 3.97 3.06 3.09 3.24 4.03
3.39 3.38 3.37 3.34 3.33 3.29 3.23 3.22 3.21 3.19 3.19 3.19 3.18 3.16 3.10 3.05 3.03 2.98
Superior vena cava syndrome Posterior reversible encephalopathy syndrome Skin defect after radiotherapy Cardiomyopathy Nephrological complications; glomerular Veno-occlusive disease Disruption of taste Extravasation of chemotherapy Fever
1.46 1.86 2.45 1.69 2.12 1.47 3.94 1.36 2.58
3.94 3.97 3.30 4.26 3.33 4.21 2.56 3.91 2.83
3.50 2.97 2.88 2.57 2.97 2.63 1.78 2.77 2.52
2.97 2.93 2.88 2.84 2.81 2.77 2.76 2.68 2.65
PAC port-a-cath, VAP venous access port, HSCT hematopoietic stem cell transplantation a
On a 5-point Likert scale ranging from 1 (low ranking) to 5 (high ranking)
b
These items were included in round 2
Support Care Cancer
study involved several panellists, we present the average measure ICC, with 95 % confidence interval (CI) and p value. Cutoff values for ICC are arbitrary, but similar to kappa statistics agreement was categorized as poor (ICC 0.8) [21]. Statistical analyses were performed using IBM SPSS version 22.0 (International Business Machines Corporation, NY, USA).
Results Between July 2013 and December 2013, panellists completed a series of two questionnaires. A total of 45 experts were invited to participate of whom 44 responded and were willing to do so. Round 1 of the Delphi survey consisted of 41 topics and comprised the full initial list of supportive care topics, as formed by the core research group (Table 1). The response rate in round 1 was 82 % (36/44 experts). Five experts passively dropped out of the panel after round 1, i.e., did not respond to several reminders for round 2. In the second round, five experts that did not return round 1 did participate in this round. Thus, the response rate in round 2 was also 82 % (36/44 experts). In all, the panel returning round 2 consisted of 14 pediatric oncologists, 11 pediatric oncology nurses, and 11 general pediatricians involved in care for childhood cancer patients. The mean scores for each supportive care topic of round 1 are presented in Table 1. In round 1, 16 topics had mean scores below 2.5 on one of the three questions and were therefore eliminated (see Table 1). The 20 highest scoring topics were included in round 2 as well as all written additions. There were 10 written additions: allergic reactions, alopecia, hemorrhagic cystitis, hypertriglyceridemia, lung function disorder, osteoporosis/avascular necrosis of the femoral head, ototoxicity, procedural sedation, peripheral neuropathy, and restrictions in daily life and activities. After Delphi round 2, the panellists determined the following topics to be prioritized in upcoming development of CPGs: (1) infection, (2) sepsis, (3) febrile neutropenia, (4) pain, (5) nausea/vomiting, (6) restrictions in daily life and activities, (7) palliative care, (8) procedural sedation, (9) terminal care, and (10) oral mucositis (Table 2). Regarding the first 9 topics of this top 10, there was agreement between panellists, i.e., more than 66 % of all panellists rated a 4 or 5 on the 5-point Likert scale of that topic. Few panellists scored these items with a 1 or 2, ranging from 0 % (infection) to 14.3 % (procedural sedation). With regard to the level of agreement, the intraclass correlation coefficient of the 20 topics presented in both rounds 1 and 2 was 0.904 (95 % CI=0.824–0.960, p
ORIGINAL ARTICLE
Development of clinical practice guidelines for supportive care in childhood cancer—prioritization of topics using a Delphi approach E. A. H. Loeffen & R. L. Mulder & L. C. M. Kremer & E. M. C. Michiels & F. C. H. Abbink & L. M. Ball & H. Segers & A. M. C. Mavinkurve-Groothuis & F. J. Smit & I. J. M. Vonk & M. D. vd Wetering & W. J. E. Tissing
Received: 22 August 2014 / Accepted: 7 December 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Introduction Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert Electronic supplementary material The online version of this article (doi:10.1007/s00520-014-2559-7) contains supplementary material, which is available to authorized users. E. A. H. Loeffen : W. J. E. Tissing (*) Department of Pediatric Oncology/Hematology, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands e-mail: [email protected] R. L. Mulder : L. C. M. Kremer : M. D. vd Wetering Department of Pediatric Oncology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands E. M. C. Michiels : I. J. M. Vonk Department of Pediatric Oncology/Hematology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The Netherlands F. C. H. Abbink Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands L. M. Ball Department of Pediatrics, Stem Cell Transplantation Unit, Leiden University Medical Center, Leiden, The Netherlands H. Segers Department of Hematology and Oncology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands A. M. C. Mavinkurve-Groothuis Department of Pediatric Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands F. J. Smit Department of Pediatrics, Maasstad Hospital, Rotterdam, The Netherlands
opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed with a well-defined methodology and include a systematic search of literature, evidence summaries, and a transparent description of the decision process for the final recommendations. Development of CPGs is time consuming; therefore, it is important to prioritize topics for which there is the greatest clinical demand. Objectives This study aims to prioritize childhood cancer supportive care topics for development of CPGs. Methods A Delphi survey consisting of two rounds was conducted to prioritize relevant childhood cancer supportive care topics for the development of CPGs. A group of experts comprising 15 pediatric oncologists, 15 pediatric oncology nurses, and 15 general pediatricians involved in care for childhood cancer patients were invited to participate. All relevant supportive care topics in childhood cancer were rated. Results In both rounds, 36 panellists (82 %) responded. Agreement between panellists was very good, with an intraclass correlation coefficient of 0.918 (95 % confidence interval (CI)=0.849–0.966, p2.5 on all three questions in round 1 were selected. This was chosen because we wanted to start supportive care guideline development with topics that are clinically most relevant, which we regarded as occurring often, being relatively severe, and having adequate treatment options. Of these, the 20 highest scoring topics were selected and presented in descending order in the second Delphi round
(see electronic supplementary material appendix II). This was limited to the 20 highest scoring items as we wanted our questionnaires to be focused on the most important topics to start CPG development with and minimize the risk of causing fatigue (and thus perhaps non-response) in our panellists. Also, all written additions were included. In this second round, the panellists were asked to rate how important it is that a CPG will be developed for the specific topic, on a 5point Likert scale ranging from 1 (unimportant) to 5 (very important). Before commencing our survey, the core research group decided to initially limit the number of rounds to two, as this Delphi survey had a prioritizing rather than a selective character. We decided to consider more rounds when there was no agreement between panellists. Each questionnaire took less than 15 min to complete. Analysis We explored agreement between panellists. We determined there was agreement when more than 66 % of all panellists rated a 4 or 5 on the 5-point Likert scale of a specific topic. In addition, the level of agreement between panellists was estimated with the intraclass correlation coefficient (ICC), set to a two-way mixed model with absolute agreement [20]. As our
Formation of core research group, compilation of list with relevant topics for supportive care in childhood cancer
Inivitation of expert panellists
45 invited 44 agreed to participate / 1 non-responder
41 supportive care topics Rate on 5-point Likert scale: - Prevalence
ROUND 1
5. frequently / 4. occasionally / 3. rarely / 2. very rarely / 1. Never
-
Severity 5. extremely / 4. very / 3. moderately / 2. slightly / 1. not (severe)
- Adequate treatment options 5. a great deal / 4. many / 3. somewhat / 2. little / 1. none
Number of respondents: 36/44 (82%) 10 written additions 21 topics excluded from round 2: - 16 topics: no mean >2.5 on all 3 questions - 5 topics: not top 20
ROUND 2
30 supportive care topics Rate on 5-point Likert scale: How important is it that a CPG will be developed for this specific topic? 5. very important / 4. important / 3. moderately important / 2. of little importance / 1. unimportant
Number of respondents: 36/44 (82%) 5 non-responders that did respond in round 1 5 additional experts that did not respond in round 1
Prioritization of childhood cancer supportive care topics for the development of clinical practice guidelines Fig. 1 Outline of the Delphi approach
Support Care Cancer Table 1
Results of the Delphi survey round 1, sorted by descending overall mean score on all 3 items
Supportive care topic
Mean scorea Prevalence
Severity
Adequate treatment options
Overall mean score
Anemiab Infectionb Nausea/vomitingb Thrombocytopeniab Painb Febrile neutropeniab Constipationb Sepsisb Malnutritionb Leukopeniab Psychosocial issuesb Tumor lysis syndrome Palliative careb Hypertensionb
4.50 4.28 4.69 4.56 4.06 4.06 4.00 2.78 3.81 4.67 4.06 2.41 2.81 3.00
2.89 3.78 3.25 3.03 3.72 3.44 2.92 4.67 3.22 3.69 3.60 3.79 4.03 3.03
4.72 4.02 4.02 4.33 4.06 3.83 4.42 3.72 4.00 2.42 3.00 4.15 3.52 4.22
4.04 4.03 3.99 3.97 3.94 3.78 3.78 3.72 3.68 3.59 3.55 3.45 3.45 3.42
Mucositis (oral) b Graft versus host disease after HSCTb Virus reactivation after HSCTb Varicella virusb Terminal careb Mucositis (gastrointestinal) b Endocrine complicationsb PAC/VAP; occlusion Thrombosis Menstruation Sub-/infertility Fatigue Sinus thrombosis Diabetes mellitus Pancreatitis Neutropenic colitis Nephrological complications; tubular Hyperviscosity syndrome
3.69 3.00 3.04 2.78 2.64 3.25 2.68 2.83 2.31 3.06 3.19 4.11 1.94 2.17 2.00 2.00 2.64 1.43
3.47 4.15 4.04 3.47 4.09 3.69 3.33 3.23 3.80 2.56 4.36 3.17 4.17 3.34 4.25 4.06 3.21 3.47
3.00 3.00 3.04 3.77 3.27 2.92 3.68 3.60 3.51 3.94 2.03 2.28 3.43 3.97 3.06 3.09 3.24 4.03
3.39 3.38 3.37 3.34 3.33 3.29 3.23 3.22 3.21 3.19 3.19 3.19 3.18 3.16 3.10 3.05 3.03 2.98
Superior vena cava syndrome Posterior reversible encephalopathy syndrome Skin defect after radiotherapy Cardiomyopathy Nephrological complications; glomerular Veno-occlusive disease Disruption of taste Extravasation of chemotherapy Fever
1.46 1.86 2.45 1.69 2.12 1.47 3.94 1.36 2.58
3.94 3.97 3.30 4.26 3.33 4.21 2.56 3.91 2.83
3.50 2.97 2.88 2.57 2.97 2.63 1.78 2.77 2.52
2.97 2.93 2.88 2.84 2.81 2.77 2.76 2.68 2.65
PAC port-a-cath, VAP venous access port, HSCT hematopoietic stem cell transplantation a
On a 5-point Likert scale ranging from 1 (low ranking) to 5 (high ranking)
b
These items were included in round 2
Support Care Cancer
study involved several panellists, we present the average measure ICC, with 95 % confidence interval (CI) and p value. Cutoff values for ICC are arbitrary, but similar to kappa statistics agreement was categorized as poor (ICC 0.8) [21]. Statistical analyses were performed using IBM SPSS version 22.0 (International Business Machines Corporation, NY, USA).
Results Between July 2013 and December 2013, panellists completed a series of two questionnaires. A total of 45 experts were invited to participate of whom 44 responded and were willing to do so. Round 1 of the Delphi survey consisted of 41 topics and comprised the full initial list of supportive care topics, as formed by the core research group (Table 1). The response rate in round 1 was 82 % (36/44 experts). Five experts passively dropped out of the panel after round 1, i.e., did not respond to several reminders for round 2. In the second round, five experts that did not return round 1 did participate in this round. Thus, the response rate in round 2 was also 82 % (36/44 experts). In all, the panel returning round 2 consisted of 14 pediatric oncologists, 11 pediatric oncology nurses, and 11 general pediatricians involved in care for childhood cancer patients. The mean scores for each supportive care topic of round 1 are presented in Table 1. In round 1, 16 topics had mean scores below 2.5 on one of the three questions and were therefore eliminated (see Table 1). The 20 highest scoring topics were included in round 2 as well as all written additions. There were 10 written additions: allergic reactions, alopecia, hemorrhagic cystitis, hypertriglyceridemia, lung function disorder, osteoporosis/avascular necrosis of the femoral head, ototoxicity, procedural sedation, peripheral neuropathy, and restrictions in daily life and activities. After Delphi round 2, the panellists determined the following topics to be prioritized in upcoming development of CPGs: (1) infection, (2) sepsis, (3) febrile neutropenia, (4) pain, (5) nausea/vomiting, (6) restrictions in daily life and activities, (7) palliative care, (8) procedural sedation, (9) terminal care, and (10) oral mucositis (Table 2). Regarding the first 9 topics of this top 10, there was agreement between panellists, i.e., more than 66 % of all panellists rated a 4 or 5 on the 5-point Likert scale of that topic. Few panellists scored these items with a 1 or 2, ranging from 0 % (infection) to 14.3 % (procedural sedation). With regard to the level of agreement, the intraclass correlation coefficient of the 20 topics presented in both rounds 1 and 2 was 0.904 (95 % CI=0.824–0.960, p
