Background
Patients are integrating complementary medicine (CM) and allopathic medicine in a variety of ways depending on their health status and health beliefs [
2,
3]. They frequently use “bundles” of therapies rather than just one therapy in isolation [
4,
5]. Typically the unit of integration in clinical environments is the patient rather than the practitioners [
6,
7]. Increasingly consumers are requesting that there be improved communication and coordination between their allopathic care and CM providers [
8]. In response to this consumer demand integrative healthcare (IHC), (also referred to as integrative medicine), has emerged over the past two decades [
9,
10]. For healthcare policy makers, care providers, practitioners and the consumer, we need to know whether IHC is effective and, if so, what structures and processes combine to exert the positive outcome. Early experimental efforts have been made to investigate the effectiveness and efficacy of this evolving IHC model of patient care [
11‐
13]. We sought to review the outcomes of recent clinical trials, explore the structure of the interventions and also to discuss the methodological approaches and issues that arise when investigating a complex mix of interventions in order to guide future research.
The varied definitions for IHC reflect differing interpretations and implementation [
11,
14‐
16]. There is a common general underlying philosophy that IHC aims to treat the whole person (physical, emotional, energetic, spiritual), using the body’s innate ability to heal itself with a blend of conventional and complementary therapies [
11,
14]. However, definitions of IHC splinter off when the structure and process of care are considered. For example, IHC may refer to the
process of patient care where allopathic and CM clinicians work as a team. The
team may operate in a multi-disciplinary or inter-disciplinary way. There may be a democratic referral system or the allopathic physician may be the gatekeeper and the CM practitioner is adjunct practitioner [
17‐
19]. In other cases, ‘integrative’ may refer to a clinician who ‘integrates’ both allopathic and CM. Further confusion is added to the typology of this field by regional variations, where “integrated” is used in the United Kingdom (UK) and parts of Europe, in the same way in which “integrative” is used in the United States (US) and Australia.
The focus of this paper is IHC defined as a patient-centred, inter-disciplinary approach where there is a combination of conventional medicine with CM with shared patient assessment, treatment planning, review and/or shared practice guidelines that are constructed and utilised during the care process. This therapeutic strategy enables each practitioner, often in conjunction with the patient, to contribute their knowledge and expertise towards providing individualized healthcare plans.
In this emerging field, there are no ‘right’ or ‘wrong’ ways for patients to experience a combination of CM and allopathic medicine. Some conditions or people may be better suited to different processes of care. However, it is important to distinguish clearly between approaches which are adjunctive or complementary therapy and not integrative as they are different entities, have different organisational and resource implications, and likely, different benefits [
14,
20]. Adjunctive or complementary is where a therapy is used in addition to allopathic medicine but not involving any shared assessment, management or review in the process of care.
Research methodology to evaluate IHC has tended to use observational designs, pre and post-test, or descriptive methods, but more recently there has been a move to the use of experimental design [
21,
22]. IHC is a ‘complex intervention’, using experimental design with a complex intervention is challenging but feasible [
23]. By ‘complex intervention’ we mean that there are many active components, which may combine to provide outcomes greater than a sum of its individual parts [
11,
24]; that may involve complex mechanisms for delivery; may be difficult to replicate (tailored to individual); and may be influenced by the environment and social context. As such it is extremely challenging to clearly articulate mechanisms of action [
23,
25]. IHC is often highly individualized, taking into consideration all aspects of a person not only one condition or symptom, has varied participant responses, with different practitioners in different settings [
26,
27]. Determining the outcomes of a complex intervention requires a combination of qualitative and quantitative methods [
23] and a consideration of the different experimental designs available [
28]. In addition to measuring outcomes, understanding the complex intervention may be aided by including a nested process evaluation or similar. Process evaluations within trials explore the implementation, receipt, and setting of an intervention and help in the interpretation of the outcome results [
24].
Hence, our review has three primary objectives:
1.
To systematically review the quality and outcomes of clinical trials of IHC
2.
To explore the design of IHC interventions, including process of care
3.
To review research methodology employed in IHC clinical trials
Methods
Eligible CM therapies were defined according to the National Institute of Complementary Medicine (NICM) [
29]. NICM has adopted, with revisions, the four domains of CM articulated by the US National Centre for Complementary and Integrative Health (NCCIH). These domains are mind-body medicine, biologically-based practices, manipulative and body-based practices and energy medicine [
30]. We included any clinical trial or protocol that was conducted in an IHC setting where there was a combination of at least one biomedical practitioner and one CM practitioner; and included an element of shared care or co-management of the patient at the stage of initial assessment, treatment plan development, case management or review. Clinical trials of multidisciplinary care where there was no element of co-management or patient sharing were excluded. Similarly, we excluded trials where the CM treatment was adjunctive and there was no shared management. Trials in integrative oncology were not examined in this review as the process of care in oncology settings differs from primary care settings, where the lead therapy is allopathic medicine and the lead clinician is the oncologist. Those conducted in an in-patient hospital setting were also excluded. Studies were also excluded which were not transferrable to a Western setting due to the different infrastructures in non-Western settings (e.g. Chinese medicine in China).
We searched PubMed (Medline), EMBASE, CINAHL, Clinical Trials Register and the Cochrane Library from inception to 30 March 2013. The following search terms were used, in various combinations: ‘integrated or integrative medicine’ or ‘healthcare’; ‘multidisciplinary care’; ‘complementary’; ‘alternative’; ‘biomedicine’; ‘conventional’; ‘mainstream’ with ‘medicine’; ‘healthcare’; ‘approach’; ‘therapies’. We also hand searched the citations of relevant papers. We included clinical trials which were randomized, non-randomized or case–control. For the purpose of this study we also included protocols for clinical trials, as we were not only focused on outcomes but on the structure and design of the integrative therapeutic intervention. Our search terms were [(Integrat* OR interdisciplinary) and (medicine OR alternat* medicine OR alternat* therap* OR complementary medicine OR healthcare)]; OR [(allopathic OR conventional OR mainstream OR orthodox OR biomedicine) AND (alternat* medicine OR alternat* therap* OR complementary medicine OR intergrat*].
To explore the structure and design of the IHC intervention we applied the structure-process-outcome model [
31]. Structure was defined as the environment in which healthcare is provided, the process as the method by which healthcare is delivered and outcome as the consequence of the healthcare provided. We were particularly interested in the process component of this model. We defined process as the way in which the healthcare is delivered – triage, diagnosis, treatment plan, and review. Central to this process are the means for collaboration to foster the “integrative” nature of the intervention. These concepts are explained below:
1.
‘Triage’ in this context refers to how a patient is ‘allocated’ into an IHC intervention or in a clinical context to a practitioner for initial assessment. In clinical practice the gatekeeper for this process may be the receptionist, the practice nurse, or general practitioner (GP) or may come from an external referral.
2.
‘Diagnosis’ refers to initial assessment where baseline data is collected in a clinical trial or where an IHC assessment is undertaken in clinical practice.
3.
‘Treatment plan’ refers to how the plan is derived, who is consulted, how it is agreed, types of treatments, duration, patient preferences and arriving at responsibility for the patient’s journey through the IHC process.
4.
‘Review’ refers to measuring outcomes at set time points, tracking patient compliance,
5.
‘Means for collaboration’: this may include meetings, shared charting, electronic medical records (EMR), corridor conversation, shared education and training, case conferences.
To review the research methodology, we considered the Medical Research Council (MRC) guidelines [
23] for evaluating complex interventions and extracted data on the following:
-
Was there a theoretical basis for the intervention and trial design?
-
ave the authors sufficiently described their intervention and the control group?
-
How was the intervention evaluated [
32]?
-
What were the context and the environment of the intervention?
-
How was implementation of the intervention assessed?
-
What was the rationale for the duration of the intervention?
Two investigators (SG and JF) independently screened all identified titles and abstracts. Full text reports were retrieved. The final decision for inclusion in the review was made by two investigators (SG and JF). The quality of the trials was also reviewed using risk of bias criteria [
33]. Each of the retrieved papers was read in its entirety. A standardized data extraction form was developed to extract data according to the set elements. Where data was missing we attempted to contact authors of the study. Data elements were then extracted and entered into a matrix according to the method of Garrard [
34]. This approach provided a systematic and concise organisation of the literature.
Discussion
The small number of IHC trials found in this review was disproportionate to the amount of literature identified. This supports the findings of Coulter et al. [
20] which concluded that research is still focused on conceptualizing and practicing IHC not on efficacy [
9]. The paucity of trials also likely reflects the difficulty in undertaking research on complex interventions such as IHC. However, there is a need for research that evaluates this integration, reflects clinical practice and provides an understanding of efficacy [
4,
47]. Reviews or summaries of this evolving field are sparse and few have focused specifically on clinical trials [
19,
48]. It is perhaps timely that we examine the reporting, structure and outcomes of recent trials within the context of emerging frameworks for researching complex interventions so as to guide future work in this field.
The theoretical rationale reported for undertaking a clinical trial of an IHC intervention was manifold. Firstly, in ‘real life’, patients frequently don’t restrict their CM use to one therapy and often seek to use a combination [
38]. Patients are usually the point at which integration occurs - ferrying results, treatment plans and x-rays between providers. It is argued that the most appropriate point of integration is the provider through IHC [
49]. Secondly, there has been much discussion about conceptual IHC models but little testing to examine how IHC may be implemented, at what cost and effectiveness [
42]. Thirdly, the combined effect or synergy of multiple interventions is hypothesised as likely to be greater than that which can be achieved by a single modality, particularly for chronic conditions [
41]. Provision of an individualised multidisciplinary intervention provides patients with greater choice, and facilitates patient participation in the decision-which is associated with better health outcomes and satisfaction [
50,
51].
Not all health conditions or diseases are suited to an IHC intervention. In the trials examined in this paper, lower back pain was the condition selected for four or five trials. It is likely that this was selected for a number of reasons. Lower back pain is a prevalent condition which has a high community and economic cost [
52]. Musculoskeletal conditions are one of the most common conditions for which people consult a CM practitioner utilizing both conventional and CM treatments alongside one another [
53,
54]. There was a clear intent within the studies to include modalities for which a positive evidence base was available. A recent systematic review and meta-analysis of the efficacy, cost-effectiveness and safety of selected CMs for neck and LBP found that CM treatments such as acupuncture, massage, spinal manipulation and mobilization, were more effective at reducing pain in the short term than no treatment, placebo, physical therapy or usual care [
52]. Trials typically examined single CM modalities in isolation, and multidisciplinary approaches rarely included CM therapies. Other types of conditions where IHC interventions might be useful are likely to be those where CM use is high, such as the for the treatment of health problems where there is unmet need and conventional care has not been able to help; that have an unpredictable course and prognosis; and that are associated with substantial pain, discomfort, or side effects from prescription drug medicine [
4,
55]. In a recent paper, IHC leaders nominated headache, back pain, arthritis and diseases across the metabolic spectrum as areas where the body of CM evidence was strong and suited an IHC trial [
56]. In another study of general practice, conditions such as musculoskeletal problems, depression, eczema, chronic pain, and irritable bowel syndrome were suggested [
57].
To understand the IHC interventions – what works and what doesn’t – we need as much transparency as possible. In the studies we reviewed development plans or protocols documented a consistent structure, process and functional intent around the variable components of IHC intervention. The completed trials in the review provided several papers reporting the results of various aspects of the intervention. In the majority of the studies this was sufficient detailed to enable the replication of elements of the design, although a clear parallel evaluation of the process would be of benefit. Only one study in our review included a nested ‘process evaluation’[
37]. Process evaluations within trials explore the implementation, receipt, and setting of an intervention and help in the interpretation of the outcome [
58]. A process evaluation embedded within future trials may assist in documenting the time taken to construct a patient profile; the skills needed to collect the information for the patient profile; the time needed to devise a treatment plan, present the plan and reach consensus; help to distinguish between essential and non-essential components of the intervention; investigate contextual factors that affect an intervention; patient responsiveness; practitioner delivery; and monitor dose [
23,
59,
60].
Equally useful to understanding the IHC interventions is to know what ‘guides’ the treatment planning and management process beyond the integrative care and management. Table
4 includes a set of ‘guiding principles’ articulated by Maiers et al.[
61]. These principles serve to clearly delineate the intent or function of the intervention, and the approach the team should aim to take. Of these five principles, all studies were guided by Principles 4, 5 and 6. It was less clear the extent to which studies were guided by the other three principles.
Table 4
Guiding principles for an IHC intervention1
Minimal intervention approach to treatment to prevent fear & castrophizing |
Goal of treatment to decrease the patients’ dependency on the health care system |
Limits on treatment should not be arbitrarily applied to care |
An evidence informed practice model based on patient presentation, clinical experience and research evidence |
Each individual is unique and treatment should be modified accordingly |
Integrative multidisciplinary approach to management |
The basic approach to the provision of care in each of the studies was guided by Principle 4: using evidence informed interventions and translate existing complementary and integrative therapies into clinical practice bringing together practitioner expertise, patient presentation and preference to form the treatment plan [
62]. In some studies, the organisational process of constructing a treatment plan was documented and this is useful for future replication. Some of the trials then documented the frequency and types of treatments patients received although the details and rationale of the actual treatments are not provided. Journal article length makes this level of reporting unfeasible. Understanding frequency and intensity of the individualised treatments may be graphically depicted in ways suggested by Perera [
63]. This may provide an indication of ‘dose’ per individual. The use of an inadequate dose may be safe and less resource intensive but ineffective.
IHC practitioners in all studies were provided with education and training of variable intent and intensity. The provision of education and training prior to study commencement demonstrated an understanding of the complexity of bringing different professional health disciplines together [
64]. Opportunities for dialogue between different practitioners and group development build mutual understanding which is considered important for success of IHC [
65,
66]. Future studies should consider the informal and formal means for collaboration and team building not only at study commencement but throughout the study. It is likely established IHC teams would operate in a more timely and cost effective fashion. Increased team cohesiveness may lead to improved safety, sharing resources, less opportunity for negative treatment interactions, reduced treatment cycles, reduced primary care visits and cost effectiveness [
42].
The studies in our review used disease specific outcome measures combined with a quality of life measure and/or a patient reported measure such as MYMOP. While disease specific measures are important, so too are outcome measures on IHC interventions that cover physical, spiritual, psychological and social domains which go beyond measuring disease specific biomedical outcomes [
67,
68]. Combinations of qualitative and quantitative measures are best placed to provide comprehensive outcome data. Philosophically, IHC and CM practices are not typically based on a mechanistic cause-effect relationship with a specific intervention for a specific symptom. Rather the approach is to bring the whole person back into ‘balance’ [
69]. One study in our review reported qualitative outcomes relating to changes in self-concept and empowerment, and benefits arising from treatment that was ‘whole-person’ focused [
46]. This supports other studies that indicate that IHC is associated with improved health related quality of life in diverse populations with substantial co-morbidity [
70]. Including measures that capture these outcomes is particularly relevant if the cost effectiveness of IHC through its capacity to reduce co-morbidities alongside disease specific symptoms and improve total well-being is to be captured [
56,
60,
69,
71].
Measuring outcomes and designing IHC interventions is further complicated by understanding that causality lies for the effectiveness of an IHC intervention lies not just with the treatment component but by enhancing the healing capacity of the patient (salutogenesis) through the social context and healing environment [
72]. The patient focused, IHC team based approach is thought to enhance this process as team members contribute unique perspectives, skills and experience to patient care [
73,
74]. Bell argues that the whole therapeutic strategy of IHC needs to be evaluated: including the patient-provider relationship, multiple conventional and CAM treatments, and the philosophical context of care as the intervention [
69]. Only one of the studies in our review included measures to attempt to evaluate this process [
75]. Future clinical trials of IHC interventions should include qualitative elements that seek to understand the ways in which this process may be fostered to maximise the specific and nonspecific healing effect of an IHC intervention.
The strengths of an IHC intervention to provide good external validity need to be considered against the inherent limitations of undertaking the evaluation of a complex intervention using an experimental design (see Table
5). Defining and articulating the “black box” of an IHC intervention is important for internal validity, generalizability and replicability [
59]. The difficulty in doing so within this type of trial design is one of the key limitations of a complex intervention. The individualised nature of IHC makes it difficult to know which component of the intervention is exerting the main effect - the combination of the therapies, the extra attention, the patient-practitioner relationship or something else not considered.
Table 5
Strengths and weakness of IHC intervention studies
Individualised, tailored | Active components are obscured |
Aims to heal the whole person | Difficult to replicate |
Suits chronic conditions | Poor internal validity |
Good external validity | Not readily transferrable to other sites as dependent on availability of modalities, certification of providers, cost |
Potential to reduce health costs | May require a long trial period with follow up to establish efficacy and cost effectiveness |
Non-specific benefits due to increased attention, health literacy and education | Non-specific benefits may be practitioner dependent. |
For the purposes of research, IHC is a therapeutic strategy not a single drug intervention. Team-based, patient-centred, integrative approaches to care present a challenge to designing rigorous studies, given IHC is typically used to provide many simultaneous treatments for multiple health concerns [
68]. Many efforts have been made to propose frameworks for researching complex healthcare such as IHC [
28,
59,
60,
69] calling on program theory [
73], whole system theory [
69,
72], utilising the Medical Research Council (MRC) framework or employing implementation, process or fidelity evaluation [
59]. Research methodology for evaluating IHC probably best involves a combination of understanding the philosophical underpinnings of IHC through whole system theory and examining it within the MRC framework. Whole systems can be defined as “approaches to healthcare in which practitioners apply bodies of knowledge and associated practices in order to maximize the patients’ capacity to achieve mental and physical balance and restore their own health, using individualised, non-reductionist approaches to diagnosis and treatment”[
76]. In the case of IHC, it is the individualised integrative therapeutic strategy that is the whole system intervention.
The MRC framework follows a typical drug development pathway but provides guidance for identifying confounders, modelling to predict how components may interact and identifying the constant and variable components of the intervention. Within the MRC framework a nested “process evaluation” within the study would provide insight on the constant and variable components of the intervention. A process evaluation would investigate contextual factors such as setting, team composition and facilitation, and examine patient-provider expectations and relationships [
24]. A process evaluation may follow some of the dimensions identified in program implementation theory: fidelity, quality of delivery, participant responsiveness, and program adaptation [
77] Each of these dimensions has been demonstrated to influence outcomes. Strategies may include interviews, focus groups, and observations alongside document reviews of clinical files and correspondence. An additional complexity is that, not unlike conventional interventions for chronic and complex conditions, research needs to be conducted over the longer term to truly capture outcomes. Jonas et al. [
72] document an evaluation model for integrative care specifically for cancer but equally applicable to understanding and evaluating IHC in primary care . The model is designed to collect data on wellbeing, behavior, clinical outcomes, bio-measures, costs and the course of treatment and compare IHC with standard healthcare practices.
A further challenge in IHC research is the preference of researchers and funders typically prefer investigations that are linear, showing a clear cause and effect, with few confounders and cost effectiveness can clearly be determined [
4] . In the US Institute of Medicine examination of contemporary approaches to CM research acknowledge the limitations of researchers trained in Western cultures, where complex “systems” with multiple levels of relationships and multiple factors which are interactive and iterative and do not fit into this preferred type of research [
4]. The typical efficacy focused RCT prescribes to the ‘average’ patient and is ‘fundamentally’ at odds with CM orientation to the ‘individual’ patient . The number of patients using CM continues to grow, as does the number of patients that desire a general practitioner who communicates about, and refers to, CM practitioners. Patients are seeking care that is tailored to their individual needs and where CM and conventional medicine collaborate [
78‐
81] with availability of these treatment options in one location being cited as desirable [
78]. These considerations aside, patients are already integrating conventional and CM therapies on their own due to a desire to access the best that both healthcare paradigms have to offer [
5]. Investigations on the efficacy, safety and cost effectiveness of an IHC model of care are warranted to guide health policy makers and consumers in decision-making and there are sufficient research and statistical methods available that enable such investigation.
Proposed RCT designs for complex interventions include pragmatic trials, factorial design, preference trials and randomised consent designs, N-of-1 designs [
28]. These trial designs may be used to address the preferences of patients, which are often strong in CM users, for an integrative approach [
82]. In considering comparators and research design, there is a broad consensus that the evaluation of IHC and CM be conducted where possible within a comparative effectiveness framework [
28,
83,
84]. The Institute of Medicine defines CER as “the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care [
85]. In selecting comparators for an experimental design, IHC lends itself with some ease to comparative effectiveness studies.
The cost effectiveness data collected in the studies in our review was comprehensive in only one study. Cost effectiveness analysis for IHC interventions should include sick leave, medication use, return-to-work and other cost-related data alongside cost of treatment course, and compliance. Sundberg et al. [
42] recommend future studies include collection of cost through using cost diaries, measuring health care visits, sick leave.
From the reviewed studies, it is difficult to determine the type and level of resources required to conduct IHC patient assessment and treatment planning. Patient assessment and enrolment in the trials were typically undertaken by one or two therapists this may increase cost. Likewise means for collaboration such as meetings are costly. Any additional duties typically come at a direct financial cost to fee-for-service practitioners or need to be compensated for within the IHC model. Conversely it is thought that within the integrative whole person approach there is considerable potential for cost-effectiveness [
56]. Some preliminary data shows that various CM interventions may be cost effective [
86]. Consumers and policy makers need to know if IHC models are cost effective for effective decision-making.
This review provides an opportunity to consider methodological challenges that arise in undertaking a trial of a multidisciplinary, complex intervention. To enable an understanding of how an individualised intervention is developed the structure and the process utilised needs to be transparent. With single interventions, internal validity is maximised by having a standard dose delivered in the same way at each trial site. Complex interventions can retain some internal validity by standardising the process, guiding principles, and structure of the intervention while allowing the ‘form’ to be adapted [
87].
A limitation of our review is that we may have omitted some studies. Our review is also limited by the inclusion criteria we selected. Our review supports the findings of Coulter et al., that the lack of a clear definition and taxonomy for integrative health care makes reviewing this field challenging [
19].