Introduction

Complementary and alternative medicine (CAM) can be defined as healthcare approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice [1]. Although not part of mainstream medicine, an increasing number of children with cancer use CAM along with conventional therapies [2]. Parents choose CAM for treatment and cure of cancer in their children [3], and also as supportive care agent to help minimize side effects of cancer treatment and to improve the general quality of life and well-being [4, 5]. The prevalence of CAM use among children with cancer is high and varies between 6 and 100%, depending on the survey sample and country, and is on average 47.2% in high-income countries [3]. CAM modalities most commonly used are herbs, diets and nutrition, homeopathy, and prayer [4, 6, 7]. Despite the high prevalence of CAM use in children with cancer, it is difficult for parents to find reliable information about it. Existing platforms developed to advise patients on CAM use for cancer, for example the website of the National Cancer Institute [8], are directed towards cancer in adults and do not specifically discuss the suitability of CAM modalities for use in children. Other information available on the internet is of poor quality [9] and frequently includes the statement: “Always consult with your child’s physician before beginning any CAM, because some therapies may interfere with standard treatment.” However, physicians typically do not receive training in CAM and have limited knowledge on the subject and so find themselves unable to discuss any possible (side) effects of CAM [10, 11]. Additionally, it is known that few parents even discuss CAM use with the pediatric oncologist [7, 12, 13]. Authoritative and reliable access to information is thus needed to support parents in their search for information on CAM modalities as potential supportive treatment options for their children with cancer.

This study describes the process and outcome of a project that aimed to develop and implement an evidence-based decision aid on CAM use for pain in order to enable parents of children with cancer to make well-informed decisions concerning CAM. Since children with cancer use CAM most often as supportive care agent [14, 15], the decision aid focused on supportive CAM care for pain.

Methods

Project design

The project had four phases of mixed methodology design (see Fig. 1) and was carried out from 2014 to 2017 by a multidisciplinary team of pediatric oncologists, members of the patient organization for parents of children with cancer (VOKK), CAM experts, and researchers. A scientific advisory board consisting of six pediatricians/pediatric oncologists supported the project team.

Fig. 1
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Project overview

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Phase 1: needs of parents

The needs of parents with respect to a decision aid on CAM use for their children with cancer were investigated by means of a survey and focus group.

Survey

In April–May 2015, a 23-item anonymous questionnaire was distributed by the VOKK to parents of children with cancer via their e-newsletter and Facebook campaign. The questionnaire was modified from previously used questionnaires on self-management instruments [16] and CAM [7, 17]. It was validated through a pilot survey among eight parents and revised accordingly with respect to rewording terms to prevent misinterpretation. The questionnaire is attached as online resource 1. Descriptive statistics were used to analyze the data by means of SPSS 22.0.

Focus group

A focus group took place in June 2015 with seven parents of children with cancer that were recruited by the VOKK. The first part of the focus group used the brainwriting technique [18] in response to the following question: What do you need in order to make a good choice about CAM use for your child? Next, the following topics were discussed: possible reasons to use CAM, information and decision-making on CAM use, communication about CAM with physicians/oncologists, and any additional requirements for a decision aid on CAM. The focus group lasted 2 h and was recorded, and field notes were taken. A directive content analysis [19] was performed to get a better understanding of the parents’ needs regarding a decision aid on CAM.

Phase 2: evidence on CAM

Evidence for CAM was investigated by means of a systematic review and meta-analyses. It was limited to pain management in children as it was not feasible within the project grant and time to perform additional systematic reviews on other cancer-related complaints.

Systematic review and meta-analysis

The review was planned and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [20]. The protocol was not registered in a database. The PICOS (Patient-Intervention-Comparison-Outcome-Study) design for the systematic review was defined as follows: Effects (reduction) on experienced pain during cancer treatment and post-treatment and occurrence of adverse events (outcome) of CAM (intervention) in comparison with no treatment, standard treatment, and placebo control or active control group (comparison) in children with cancer (patient) reported in prospective controlled studies (study). Between December 2015 and March 2016, the PubMed, EMBASE, Cochrane, and CINAHL were searched. Search terms and strings are attached as online resource 2. Inclusion criteria were peer-reviewed prospective controlled studies in children (0–18 years) with any type of cancer undergoing a CAM intervention (as defined by the National Center for Complementary and Alternative Medicine [21]) published in English or Dutch language. The primary outcome was pain (any pain-related outcome), and the secondary outcome was reported CAM-related adverse events. Two researchers performed the selection of studies, data extraction, and risk of bias assessments. Any instances of disagreement were resolved by consultation with a third researcher. The risk of bias assessment was done according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) handbook [22]. The GRADE approach was used to facilitate the overall quality of each outcome and to assess risk of bias across studies [23]. Meta-analysis was performed in cases where the results of two or more randomized clinical trials (RCTs) per CAM modality could be pooled using RevMan 5.3 (Cochrane collaboration) and GRADEpro (version 3.6) for different scores related to pain across interventions. I2 was used to test for heterogeneity in judging consistency of evidence.

Clinical experience

Six pediatric oncologists working at integrative pediatric oncology clinics in Canada, the USA, Germany, and Italy were interviewed to collect information related to the use and safety of CAM in the treatment of pain in children with cancer. These experts were identified at the International Congress on Integrative Medicine and Health (Las Vegas, 2016). The interview guide consisted of seven questions (see online resource 3). Interviews were conducted face-to-face or via Skype, were recorded, and varied in length from 30 to 60 min. The content was analyzed and categorized as follows: CAM modalities, effects, treatment phase, type of pain and patient, complaints, and side effects.

Phase 3: development decision aid

The objective of phase 3 was to combine information on research evidence and clinical expertise in order to inform recommendations and decision-making regarding CAM use for pain management in children with cancer. A 3-h expert meeting was organized in June 2016 consisting of a balanced mix of pediatric oncologists, pediatricians, pediatric nurses, parents, CAM experts, researchers, and members of the patient organization. The meeting included 14 participants in total. Preceding the expert meeting, all participants read the outcome and underlying documentation of phase 2 and were informed about the procedure and steps in the meeting, which followed the seven-step approach of GRADE [22]. Other CAM-related contextual factors taken into consideration included whether the CAM treatment was safe, feasible to implement, could be taught and practiced by the children or the parents independently, was practiced individually or as a group, and whether it was a facilitator for conventional treatment. Based on the recommendations and decisions that were reached in the expert meeting and on the results from the earlier phases, three text writers (representing the patient, CAM, and scientific perspective) wrote the content for the decision aid. The concept structure of the decision aid was developed by members of the project team in parallel with technical support from KSMT design (The Hague, the Netherlands).

Phase 4: evaluation of decision aid

The content and structure of the decision aid were evaluated through interviews and a short questionnaire (see online resource 4) administered to the VOKK, three pediatric oncologists, and 13 parents. Evaluation was based on the look and feel, structure, ease of comprehension, usability, navigation, usefulness in decision-making, and interface. Analysis of feedback was performed by one researcher and the content was adapted accordingly.

Results

Phase 1: needs of parents

In order to develop a practical and useful decision aid on CAM use that is likely to be adopted by families affected by cancer, the project started with investigation of the needs of the parents.

Survey

Among those surveyed, 70 parents responded. Mothers made up the majority of respondents (93%). Among all respondents, most had a child with leukemia (55%) or a brain tumor (17%). Among the cancer-affected children of respondents, 31% were currently in treatment and 38% had finished treatment more than 1 year ago. More than half (56%) reported CAM use for their child. Among those who reported CAM, the use of food supplements/vitamins (32%), massage (22%), and homeopathy (22%) were most mentioned. One-third of those using CAM for their child had searched for information about the CAM treatment before use. Sources included the Internet (37%), family/friends (37%), and CAM practitioners (26%). Eighty-eight percent of respondents thought it was important to receive/find good quality information on CAM. Most respondents (79%) had a need for information on CAM following their child’s cancer diagnosis, including 38% just after diagnosis, 45% during the first year after cancer treatment, 34% more than a year following cancer treatment, and 14% in the palliative phase. Parents sought information on CAM for treatment of fatigue (62%), anxiety (47%), pain (46%), weakened immune system (44%), sleeping problems (42%), nausea/vomiting (35%), low mood (29%), decreased appetite (27%), intestinal problems (22%), concentration problems (16%), and weight loss (11%). Parents mentioned a need for a decision aid to support their discussions of CAM treatments with their physician (60%), to find reliable CAM practitioners (59%), for education regarding possible CAM use (45%), for support in asking questions of CAM experts (43%), and as a resource for reading about other parents’ experiences with CAM (40%). Preferences for the form of the decision aid were website (62%), app (23%), or informational brochure/leaflet (12%). Preference of most respondents was that the decision aid be accessible via the treating pediatric oncologist (88%) or VOKK (83%).

Focus group

Direct content analysis was performed on five themes: (1) Search strategies: Parents usually start searching for CAM options after their child has been receiving treatment for some time as closer to time of diagnosis they have too much information to process. Parents report searching the Internet for CAM modalities effective for specific complaints or cancer types, for finding reliable CAM practitioners, and for information on whether particular CAM modalities can be combined with cancer treatment. (2) Decision-making: Decisions on the use of CAM are mostly based on the positive experiences of family/friends, on parent’s personal experiences with CAM, or on the availability of evidence for a particular CAM modality. (3) Format of the decision aid: A website with a search function for complaint, type of cancer, and CAM modality, along with a chat function allowing interaction with other parents and a CAM expert who can answer CAM-related questions. (4) Function of the decision aid: To allow the parents make their own decisions with regard to CAM, and also as a tool to discuss the outcome on CAM with the pediatric oncologist. (5) Content of the decision aid: Description of positive effects of particular CAM modalities, evidence for their use, potential side effects, and possible interference with cancer treatment.

Phase 2: evidence on CAM

Based on the results of phase 1, the project team needed to make a decision on the focus of the decision aid. Since there are more than 1800 CAM modalities [24] and performing systematic reviews to collect evidence-based information on all these modalities is time-consuming, it was not feasible to develop a decision aid on all childhood cancer-related complaints for which parents in phase 1 wanted information about. It was decided to focus on CAM use for pain during cancer treatment and post-treatment because (1) pain was in the top three complaints that parents wanted information about in phase 1 and (2) the Dutch Childhood Oncology Group (DCOG; www.skion.nl) was developing clinical guidelines for treatment of pain, so a joint venture was planned.

Systematic review on CAM for pain

Figure 2 shows the study selection process. A total of 6936 records were identified from searches, of which11 RCTs met the criteria for GRADE analysis [25,26,27,28,29,30,31,32,33,34,35]. An additional 18 articles served as input for phase 3 (see online resource 5). The characteristics of the included RCTs are summarized in Table 1. RCTs were found for five CAM modalities: hypnotherapy (N = 5), massage (N = 3), healing touch (N = 1), music therapy (N = 1), and mind-body intervention (N = 1). Ten out of 11 studies investigated the changes in pain related to procedures such as venapuncture, lumbar puncture, or bone marrow aspiration. The 11 studies included children with all types of cancer. The quality of studies was moderate to high for the RCTs on hypnotherapy and low to moderate for the other CAM modalities (Table 1). Since the studies differed with respect to pain scales, control groups, and number of RCTs per CAM modality, pooled effects on the primary outcome could only be analyzed for hypnotherapy and massage (Table 2). There was high-quality evidence that hypnotherapy significantly reduces cancer-related procedural pain in children; the pooled effect was statistically significant (MD, − 1.37; 95% CI, − 1.60, − 1.15; P < 0.00001) compared with standard care [27,28,29], and statistically significant (MD, − 1.13; 95% CI, − 1.34, − 0.94; P < 0.00001) compared with an attention-control group [26,27,28,29] (Table 2). Both analyses showed significant heterogeneities (P < 0.001), with I2 values of 87% in comparison with standard care and 86% in comparison with attention-control. One high-quality study on hypnotherapy by Smith et al. [34] was not included in the meta-analysis because it used a different VAS scale and outcome data were only reported for children with high hypnotizability and children with low hypnotizability. There was low-quality evidence for no effect of massage (Swedish/acupressure and effleurage/petrissage techniques) on cancer-related procedural pain compared with standard care; the pooled effect of two studies was not significantly different (MD, − 0.77; 95% CI, − 1.82, 0.28; P = 0.15, heterogeneity I2 = 0%, P = 0.80) (Table 2). No evidence was found that the five CAM modalities were unsafe to treat pain in children with cancer.

Fig. 2
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Flow diagram of study selection and identification

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Table 1 Literature review table—included studies
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Table 2 GRADE evidence profile
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Since it is more challenging to conduct trials in children than in adults [36], especially with regard to cancer, the number of pediatric patients in studies is still limited [37]. Therefore, in order to collect more information on the appropriate use of specific CAM modalities for pain management in children with cancer, it was decided to investigate the clinical experiences of pediatric oncologists with expertise in CAM. Experts had positive clinical experience with all five CAM modalities that were found in the systematic review (see online resource 6).

Phase 3: development decision aid

Data of the systematic review and the clinical experience from pediatric oncologist, as obtained in phase 2, formed the main input for the development of the decision aid in phase 3. A crucial step in phase 3 was to reach consensus among stakeholders with respect to recommendations on CAM use. Five CAM modalities (hypnotherapy, mind-body techniques, massage, healing touch, and music therapy) were included in the decision aid based on the results from the systematic review. The clinical expert opinions of pediatric oncologists in Integrative Oncology as well as patients’ needs and preferences were considered important supplementary sources of information for these five CAM modalities. Recommendations were given for each CAM modality (see Table 3). The project team processed the information from the phase 2 literature analysis and expert meeting into a concept structure for a website-based decision aid, and the content was written by three text writers.

Table 3 Recommendations on CAM use for pain management in children with cancer
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Phase 4: evaluation and implementation of decision aid

The content and structure of the decision aid as developed in phase 3 was evaluated by the VOKK, parents, and pediatric oncologists. Feedback included comments on the inclusion of too much scientific terminology that some information was too general in nature, to improve clarity with regard to which CAM modalities are supported by evidence and with regard to the information on which the content was based. According to the preference of parents (see “Phase 1: needs of parents” under the “Results” section), the decision aid was linked to the VOKK, the Dutch organization for parents of children with cancer: http://www.complementairezorg-vokk.nl/.

The overall structure of the decision aid is depicted in Fig. 3. To facilitate its use, the VOKK announced the launch of the decision aid via the newsletter, website, and Facebook page and via an article in their printed news magazine. A “business” card of the decision aid was developed for the Princess Máxima Center for pediatric oncology, the recently established high-complex care center for childhood cancer in the Netherlands [38], to make parents aware of the existence of the decision aid. Awareness among healthcare professionals was created via DCOG, and the decision aid was introduced in education programs at the Princess Máxima Center and at the University Medical Center in Utrecht. The Louis Bolk Institute assumed ownership and responsibility for maintenance and updating of the decision aid.

Fig. 3
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Visual overview structure decision aid

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Discussion

To the best of our knowledge, this is the first study that reports on the development of an evidence-based decision aid for supportive CAM care on pain in childhood cancer. The decision aid was primarily developed as a website for parents, but is considered more than an information website. A decision aid is defined as an evidence-based tool designed to help patients make specific and deliberate choices about available healthcare options [39]. In order to facilitate patient-centered decision-making, the totality of evidence in a decision aid should comprise four pillars: research evidence, practice evidence, patient evidence, and contextual factors [40]. First, the decision aid provides evidence-based information. In addition to high-quality research evidence, it incorporates information from practice (clinical experience), contextual factors (feasibility of implementation), and patient preferences. Second, it is patient-centered and facilitates decision-making by parents of children with cancer, for example helping them to decide whether or not to use CAM as supportive care for their child. Third, it supports parents to recognize possible benefits and harm related to their decision about CAM use for their child. Finally, the decision aid is designed to be helpful for parents in discussions of CAM with healthcare professionals. Although few parents currently discuss CAM use with the treating pediatric oncologist [7, 12, 13], the majority want to receive information and discuss it with them [7]. The use of the decision aid as a tool has the potential to improve communication on CAM between parents and healthcare providers.

One of the major limitations of the current decision aid is that it is limited to decision-making on CAM modalities for pain relief. The potential effectiveness of the five CAM modalities included in the decision aid, or of other CAM modalities in addressing other complaints than pain, was not investigated. Recently, a RCT in children undergoing hematopoietic stem cell transplants reported that although music therapy did not significantly reduce pain compared with control, it significantly enhanced health-related quality of life [41]. Another major limitation of this study is that it did not evaluate whether the current decision aid actually improved parents’ knowledge regarding CAM treatment options, or whether it reduced the decisional conflict stemming from feeling uninformed and unclear about treatment options. Future studies are planned to evaluate the effectiveness of the decision aid for parents in practice and, additionally, to assess its use in communication between parents and healthcare professionals. In the present study, parents wanted information on CAM for a broad spectrum of symptoms related to childhood cancer treatment, i.e., fatigue, anxiety, and pain. This is in line with a previous study, demonstrating that parents perceive high symptom burden in their children with cancer, pain being the most problematic area [42]. Next steps recommended concern expanding the decision aid on CAM for other pediatric cancer-related complaints, as to provide further evidence on how CAM modalities may contribute to reduce the symptom burden in children with cancer. In addition, further investigations are warranted as to disclose potential harmful interactions between CAM remedies and cancer drugs.

A strength of the present study is that the decision aid was developed based on the true needs of parents and was developed by a multidisciplinary team who consider CAM worthy of serious evaluation, so that the perspectives and contextual factors of stakeholders in childhood cancer were taken into account.

In conclusion, an evidence-based decision aid was developed to support parents of children with cancer in making decisions on possible CAM treatment for pain management. Next steps will be to expand the website with evidence for CAM on other childhood cancer-related complaints and to evaluate its use in practice.