A systematic literature review of the assessment of treatment burden experienced by patients and their caregivers.

Background

Multimorbidity now affects 65% of older adults in the United States [ 1 ]. Many people live a significant portion of their lives with long-term medical conditions that require constant input both from the health care system and from the patient themselves [ 2 ]. As the complexity and choice of treatments have grown, many patients and their families struggle to manage the responsibilities and burdens that come with managing multiple chronic conditions. Treatment burden refers to the impact on patient functioning and well-being imposed by the demands on a patient and their caregiver’s time and energy by both treatments and aspects of self-care such as health monitoring, diet and exercise [ 3 ].

Treatment burden usually adds to the symptoms and physical and psychological difficulties imposed by the condition itself [ 4 ]. Treatment burden is patient specific. For some individuals, burden may be transient in the context of an acute illness and gladly tolerated on a temporary basis in the service of achieving a health care-related goal. For others, the burden of taking multiple oral medications may be accepted, but the challenge of self-administering injections may be too great to overcome [ 5 ]. Many tasks on their own appear simple –such as taking new medications, organizing and undergoing tests, and making lifestyle changes. When the number of tasks continues to rise, however, and begins to interfere with work, family and other commitments, the burden of treatment on patients and their families can be very high [ 6 , 7 ]. Family members often find themselves in the untrained role of informal caregiver learning to give injections, manage polypharmacy or navigate the healthcare system [ 8 ]. Too often providers do not recognize the burdens experienced by patients and caregivers and this lack of recognition can contribute to the difficulties of patients to adhere to the provider recommended management of their condition [ 9 ].

Person-centered care seeks to minimize treatment burden by tailoring treatment regimens to the realities of the daily lives of individual patients and their particular goals by engaging in Minimally Disruptive Medicine [ 10 ]. Reliably and efficiently assessing treatment burden in clinical practice would alert healthcare professionals to patient or caregiver distress, allow healthcare professionals to develop a partnership with the patient, and encourage them to work together to agree upon treatment strategies that are both effective and acceptable for the patient and caregiver. Although multiple studies have documented treatment burden [ 11 ] and developed tools to assess the burden, no common approach or assessment instruments have been employed in clinical practice. Importantly, we do not know the extent to which these approaches accommodate measurement of treatment burden in the context of multimorbidity.

We performed a systematic literature review to identify articles or sources assessing the treatment burden experienced by adult patients and caregivers. Our ultimate aim is to develop a treatment-burden-related quality indicator that could work across a range of patients with multiple chronic conditions receiving home-based medical care.

Methods

Definition of treatment burden

Building upon previous definitions [ 3 ] we defined treatment burden as the effort required by the patient or caregiver to manage the medical conditions of the patient and the impact that this has on their lives. Management includes treatments and self-care or caregiver tasks required to address, treat or monitor specific conditions. Perceived burden varies depending on factors such as available time, additional medical conditions, other responsibilities and treatment related factors such as cost, intensity, difficulty and complexity [ 12 , 13 ].

Search strategy

The search was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [ 14 ] and using similar methodology to other systematic reviews performed by our group [ 15 , 16 ] . PRISMA provides an evidence-based minimum set of items for reporting to allow a transparent and complete reporting of systematic reviews. Working with a clinical informationist, an expert in the area of treatment burden (CB) and our research team we identified and refined MESH (Medical Subject Headlines used for indexing articles in PubMed) and keyword search terms related to treatment burden. Sample searches were performed to identify articles deemed highly relevant. After finalizing the search terms, systematic searches were performed of both the peer-reviewed and grey literature. Following the initial PubMed search, search terms were further refined to facilitate searches of the Cochrane library, The Cumulative Index to Nursing & Allied Health (CINAHL), EMBASE, Web of Science, SCOPUS, the New York Academy of Medicine Grey Literature Review, the NLM catalog and the database of ProQuest Digital Theses and Dissertations. The search terms used in the final PubMed search are shown in Fig. 1 . Searches were performed for articles relating to humans from 1997 onwards and those in the English language and were performed in March 2019. Similar searches were performed of relevant journals not indexed in Medline. To complete the grey literature review, the first 300 hits from a google search were reviewed for relevance. A search was also performed of relevant guidelines as well as the websites of advocacy groups. Hand searches were conducted of the reference lists of relevant retrieved articles. Fig. 1 Final pub-med search

Inclusion, exclusion, and assessment of studies

All articles were entered into reference manager, Endnote v7. Duplicates were removed and the search results were reviewed in a step wise process. First, we screened the titles and abstracts of retrieved articles for relevance to the study aim. Next, full length manuscripts or publications were obtained for any studies that discussed or provided specific recommendations for assessing treatment burden. Articles which referred to any method (qualitative or quantitative) of assessing the treatment burden experienced by patients, caregivers or both for either research or clinical care were included. Articles discussing treatment burden both in general or in relation to one or more specific medical conditions were included. Publications not addressing treatment burden experienced by patients (e.g. only focusing on the overall disease burden, not treatment specific, or the burden of cost on the healthcare system) were excluded as were articles describing treatment burden in pediatric populations. Information on study design, population studied, chronic disease(s), aims, findings, outcomes and measures of treatment burden were extracted from selected articles, publications and guidelines and entered into an excel spreadsheet.

Results

Search results

Following a review of the title and abstracts of 1987 publications, our systematic review of the peer-reviewed literature identified forty-five relevant articles. A further three items (1 book and 2 PhD theses) were identified from a search of 447 titles and abstracts from the grey literature. Forty-eight articles are included in the final sample. The search strategy and results are outlined in Fig. 2 , and relevant articles are summarized in Tables 1 and 2 and Additional file 1 . Fig. 2 Flow diagram of data sources, search results and process for identification of relevant articles Table 1 Qualitative papers exploring the treatment burden experienced by patients and caregivers Study Disease Purpose of study Specific question / topics asked [ 30 ] Asthma Compare the burden of disease and treatment in patients with asthma. What is your experience of having asthma? How does it affect your life? What is your experience of asthma medicines? How effective are they and do you experience side effects? [ 4 ] Chronic conditions Types and consequences of treatment burden. What are the effects of excessive treatment burden in patients with multimorbidity? How might treatment burden be decreased in patients with multimorbidity? [ 22 ] Chronic Conditions Burden of treatment regimens on consumers. Questions included perspectives on the burden of chronic illness, the burden of treatment and alleviating treatment burden. [ 25 ] Chronic conditions Explored treatment burden among people with chronic conditions. Questions explored the extent and duration of illness, difficulties with medications, finances, relationship with healthcare professionals and daily practical challenges. [ 24 ] Chronic Conditions Factors that patients draw on to lessen burden. How patients cared for their conditions and the impact that care had on them, including their personal life, social situation, and work. Factors that made their care easier or more difficult? [ 26 ] Chronic conditions ICAN Discussion Aid Completed by patients and used during the encounter between patients and health professionals to understand patient capacity, workload, and treatment burden. [ 20 ] Chronic conditions Review qualitative literature on burden of treatment 9 studies included. Which components form the burden of treatment in the view of patients with multimorbidity? How is the patient-experienced burden of treatment in patients with multimorbidity conceptualized in the included studies? [ 19 ] COPD, lung cancer Review features of treatment burden in these conditions 127 articles included. [ 27 ] COPD Explore understanding and experiences of treatment burden Explored burden from prescribed drug treatment, required health-behavior changes, and interactions with health professionals or health services. Treatment burden was then graded. [ 18 ] Heart Failure Review qualitative literature of end-stage heart failure. 16 different articles included [ 21 ] Heart Failure Is Normalization Process Theory a useful framework to treatment burden in heart failure? Questions included how the condition affected the patient’s life at home, ability to perform daily chores, routine, social life/leisure activities as well as if the condition prevented them from doing anything they wish to do? [ 28 ] Heart Failure WALT instrument used to assess burden of therapy Assessed willingness to undergo therapy given the burden imposed by the therapy, the health state, likelihood of the health state and expected life extension, resulting from the therapy. [ 29 ] CHF, COPD or cancer Effect of treatment burden on treatment preferences at the end of life. Questions on a participant’s desire for treatment: the treatment itself, quality-of-life considerations, and the issue of the uncertainty of the outcome. [ 38 ] Cystic fibrosis Explore the perceived treatment burden of patients and its correlation with other factors. To what extent do your treatments make your daily life more difficult? How much time do you currently spend each day on your treatments? How difficult is it for you to do your treatments (including medications) each day? [ 23 ] Macular Degeneration Explore the psychosocial impact of repeated intravitreal injections Semi-structured, one-on-one interviews on treatment burden and satisfaction, tolerability, barriers to adherence, treatment motivation, and patient education. [ 31 ] PEG Report the burden of treatment from the patient perspective. Do you think that having a PEG has changed your life in any way? Is there anything which has been especially difficult, in living with a PEG? [ 17 ] Stroke Examine the qualitative literature on stroke and treatment burden. 69 different studies included [ 32 ] Stroke Create a conceptual model of treatment burden and patient capacity Coding framework informed by Normalisation Process Theory (NPT) to organize the patient workload of chronic disease management into the following broad categories: sense-making; interacting with others; enacting management strategies; and appraisal work. PEG Percutaneous endoscopic gastrostomies, WALT Willingness to Access Life-Sustaining Treatment, CHF Congestive Heart Failure, COPD Chronic obstructive pulmonary disease, ICAN Instrument for Patient Capacity Assessment Table 2 Quantitative studies assessing treatment burden and the specific instruments or question used Reference Disease Instrument or question used to assess treatment burden [ 65 ] Asthma Satisfaction with Inhaled Asthma Treatment Questionnaire [ 35 ] Bronchiectasis Quality Of Life -B 3.0 questionnaire [ 45 ] Cancer (breast) Quality of life questionnaire [ 41 ] Cancer (Lung) Number of encounter days (inpatient or outpatient) [ 40 ] Cancer (seminoma) Number of treatment episodes. [ 34 ] Cancer, congestive heart failure or chronic obstructive pulmonary disease Willingness to Access life-Sustaining Treatment (WALT) instrument [ 44 ] Celiac disease Participants asked to rate 4 domains on a scale of 0–100: difficulty in following treatment, perceived importance of following treatment, disease-specific health and overall health. [ 52 ] Chronic conditions Living with Medicines Questionnaire V3 (LMQ-3) [ 51 ] Chronic conditions Patient Experience with Treatment and Self-management (PETS) [ 57 ] Diabetes [ 7 , 54 ] Chronic conditions Health Care Task Difficulty. [ 47 ] Chronic conditions Treatment Burden Questionnaire (13-item) [ 48 ] HIV [ 11 ] Chronic conditions Treatment Burden Questionnaire (7-item) [ 46 , 49 , 59 ] Chronic conditions Adapted Treatment Burden Questionnaire (15-item) to include financial burden question and side effects of medication question [ 53 ] Chronic conditions Exercise Therapy Burden Questionnaire (ETBQ) [ 50 ] Multimorbidity Multimorbidity Treatment Burden Questionnaire (MTBQ) [ 38 ] Cystic Fibrosis As part of the CFQ-R, treatment burden was assessed with 3 questions. [ 37 ] Diabetes Diabetes Treatment Burden Questionnaire (DTBQ) [ 43 ] Lupus nephritis Likert scale rating of treatment burden. [ 56 ] Medicare beneficiaries 4 questions about things patients are asked to do to stay healthy or treat health problems. [ 36 ] Psoriasis Dermatology Life Quality Index [ 42 ] Stroke Polypharmacy used as a measure of treatment burden [ 39 ] Urinary Incontinence Patient Satisfaction Questionnaire CHQ: Child health questionnaire; CFQ-R: Cystic Fibrosis Questionnaire – Revised; TBQ: Treatment Burden Questionnaire; Diabetes Treatment Burden Questionnaire: DTBQ; Patient Experience with Treatment and Self-Management: PETS; Living with Medicines Questionnaire V3: LMQ-3; Medicine Regimen Complexity Index: MRCI; Exercise Therapy Burden Questionnaire: ETBQ; Multimorbidity Treatment Burden Questionnaire (MTBQ), Willingness to Access Life-Sustaining Treatment: WALT

Population and study setting

Thirty-four of the 48 articles (70.8%) discussed treatment burden associated with specific conditions e.g. heart failure, cancer, cystic fibrosis with the remaining fourteen articles focusing on patients with multiple chronic conditions. Forty-six articles examined treatment burden experienced by patients and six discussed that experienced by caregivers. Three articles [ 17 – 19 ] reviewed the qualitative literature on treatment burden and a chronic condition (stroke, heart failure, respiratory disease) and one article [ 20 ] reviewed it in persons with multiple chronic conditions. Quantitative assessment of treatment burden was reported in 30 studies and 18 articles described qualitative approaches.

Qualitative studies of assessment of treatment burden

Articles using qualitative analyses of focus group or semi-structured interview data identified the main dimensions of treatment burden experienced by patients [ 4 , 17 – 22 ], factors which increase burden [ 19 , 20 ] and methods by which patients decrease burden [ 20 , 23 ]. Treatment burden was present both in populations with one specific condition and in those experiencing multiple chronic conditions. In the stroke and heart failure populations the four main dimensions of treatment burden identified through the qualitative literature were coherence (understanding the condition and its implications), treatment and management, appraisal (juggling, monitoring and adjusting treatments) and relationship work (efforts to engage with health professionals, family and patients for help and support) [ 17 , 21 ]. Table 1 .

Specific conditions generated specific burdens, for example, patients with percutaneous endoscopic gastrostomies were most burdened by lifestyle restrictions and practical limitations [ 31 ]. The anxiety of receiving intravitreal injections was a source of treatment related burden in macular degeneration [ 23 ]. Patients with lung cancer and COPD reported reduced capacity to manage workload due to illness/smoking-related stigma [ 19 ]. Many people described the burden of educating themselves about their disease and learning how to self-manage their condition [ 19 , 27 , 30 , 32 ]. Patients with chronic conditions and their unpaid caregivers felt that financial burden was the most problematic for them but also felt burdened by time and travel issues, medications and healthcare access [ 20 , 22 , 23 , 25 ]. Many treatment related burdens described in relation to a specific condition could also apply to other conditions, for example, multiple myeloma treatment which led to a substantial psychological and physical burden on patients disrupting social activities, decreasing independence and impacting relationships [ 33 ].

One group used the Instrument for Patient Capacity Assessment (ICAN) discussion aid during the physician encounter to promote discussion in order to understand patient capacity, workload, and treatment burden [ 26 ]. One of the questions in the aid asks “What are the things that your doctors or clinic have asked you to do to care for your health?” Examples are given and patients are asked “ Do you feel that they are a help, a burden, or both?”

Treatment burden was increased by polypharmacy, multimorbidity, reduced physical, financial and cognitive capacity, barriers to accessing services, fragmented and poorly organized care, lack of continuity of care and inadequate communication between healthcare professionals [ 19 – 21 ]. The same burden was decreased in people with multiple chronic conditions by using problem or emotion focused strategies (e.g. technology, routinizing self-care, enlisting support, maintaining a positive attitude, spirituality), adaptation, prioritization, receiving social support and identifying the positive aspects of health care [ 20 , 24 ]. Capacity to manage treatment burden was influenced by personal attributes and skills, physical and cognitive abilities, support network, financial status, life workload and environment [ 32 ]. Patient preferences were variable based on the substantial differences within the population studied regarding willingness to undergo more or less burdensome therapies [ 28 ]. When preferences were tracked over time participants became less willing to endure a high burden of therapy to avoid death [ 29 ]. Concern about cognitive disability also rose with time, with participants becoming less willing to accept even low risks of cognitive disability when receiving treatments aimed to prolong life [ 34 ].

Quantitative studies of assessment of treatment burden

Many instruments and measures used to assess treatment burden were disease-specific (e.g. the Quality of Life-Bronchiectasis (QOL-B) questionnaire [ 35 ], the Dermatology Life Quality Index [ 36 ] or the Diabetic Treatment Burden Questionnaire [ 37 ]). In general, these instruments assessed treatment burden as part of longer quality of life questionnaires [ 33 , 36 – 39 ]. Studies describing disease-specific assessments of treatment burden tended to be in younger populations and the conditions studied required specific and time-consuming interventions on the part of the patient e.g. applying creams in psoriasis, respiratory treatments in cystic fibrosis or dietary restrictions in celiac disease. Three studies in cancer patients receiving short term intensive chemotherapy and radiotherapy sessions used number of treatment episodes [ 40 ], number of encounter days and number of physicians involved in care [ 41 ] as surrogate markers of treatment burden. Polypharmacy was also used as a surrogate marker of treatment burden in stroke and cancer patients [ 41 , 42 ] where a higher number of medications indicated increased burden of treatment. Open ended questions or linear analog indicators of burden were also used by some groups [ 43 – 45 ] with questions such as “Overall, how much are you bothered by any treatment related difficulties” or “the treatment so far was…” with responses ranging from not burdensome [ 1 ] to extremely burdensome [ 10 ].

Twelve studies described the assessment of treatment burden in patients with multiple chronic conditions. A variety of assessment tools were used with each reflecting the complexity of managing multiple chronic conditions by asking about many aspects of burden. Despite this shared purpose, these assessment instruments varied in content and length. Five studies used the Treatment Burden Questionnaire (TBQ) which rates fifteen items which may be associated with treatment burden on a 0–10 scale [ 11 , 46 – 49 ]. The Multimorbidity Treatment Burden Questionnaire (MTBQ) is a concise (10 item) measure of treatment burden designed specifically for patients with multimorbidity [ 50 ]. The authors recommend its use in clinical practice to highlight specific problem areas for patients with multimorbidity such as problems with medications or lifestyle changes. The Willingness to Accept Life-Sustaining Treatment (WALT) instrument was used to examine, among other things, how treatment burden and treatment outcomes influence patient preferences across a wide range of chronic conditions [ 34 ]. Another group used a 78-item measure, the Patient Experience with Treatment and Self-management (PETS) measure. This explores many aspects of treatment burden including learning about health conditions, medications, appointments, monitoring health, exercise, diet, equipment, interpersonal challenges, expenses, healthcare providers, difficulty with services, social limitations, and exhaustion [ 51 ]. The Living with Medicines Questionnaire uses a Likert scale to rate 41 questions covering eight domains of medication burden [ 52 ]. Exercise is recommended as part of the management of many chronic conditions and its burden can be measured using the 10-item Exercise Therapy Burden Questionnaire [ 53 ]. The Health Care Task Difficulty (HCTD) scale assesses 8 different health care tasks [ 54 ]. The National Health and Aging Trends Study (NHATS) brief measure of treatment burden fielded in 2012 asked participants to reflect on the things they are asked to do to stay healthy or treat health problems (e.g. managing medicines, getting tests done, watching weight and blood pressure) [ 55 , 56 ]. Some measures initially developed for chronic conditions were later adapted for specific conditions e.g. PETS for the diabetic population [ 57 ]. Additional detail on the instruments used to assess treatment burden are in Table 2 and Additional file 1 .

Assessment of treatment burden experienced by caregivers

Six studies described assessing treatment burden experienced by caregivers through qualitative interview [ 19 , 22 , 25 ] and assessment tools (HCTD, TBQ) [ 7 , 56 ] and survey [ 56 ]. Giovannetti used the HCTD scale to describe caregiver’s difficulty in assisting multimorbid older adults with eight health care tasks and found that difficulty increased with both advancing age of the caregiver and the number of healthcare tasks for which they were providing assistance [ 7 ]. Higher HCTD scores were associated with increased caregiver strain and depressive symptoms. Representatives from consumer health organizations representing individuals with chronic conditions highlighted the frustration and distress experienced by caregivers from treatment burden, citing examples of social isolation, deteriorating health, self-neglect, lack of support and marginalization resulting from the burden of their family member’s treatment [ 22 ]. In a study of individuals with chronic conditions and their caregivers [ 25 ], financial burden was the most widely discussed burden arising from treatment of chronic illness even in the Australian setting with federally provided universal health care. Caregivers described feelings of guilt caused by prioritizing the cost of medication over the broader needs of their family. Travelling with the person they cared for to access health services was also reported to be particularly burdensome for caregivers, mainly due to the logistics of transportation and parking falling to them. The importance of financial burden was echoed in recent studies on patient reported treatment burden in both Australia [ 27 ] and also in fee for service systems such as the United States where the burden is likely to be even higher [ 20 ].

In another study of the treatment burden experienced by people with chronic conditions [ 56 ] a quarter of participants with chronic conditions were also unpaid caregivers to another individual with a chronic condition. In this NHATS population having an unpaid caregiver predicted a substantial increase in patient reported treatment burden, however, being both a patient and carer did not have an effect on treatment burden. The authors hypothesized that this seemingly paradoxical effect could potentially be due to the differing psychological effects with care recipients experiencing feelings of guilt for burdening a family member while caregivers may feel a sense of self-worth and satisfaction while caring for a loved one. Other studies [ 19 ] also referred to the positive effects of caregiving describing caregiver participation in the treatment workload as practically onerous but an affirmation of the strength of the caregiver’s relationship with the patient. Despite this many caregivers reported feeling compelled to take on a caregiving role and described balancing treatment workload with their everyday life as being extremely demanding and limiting.

Discussion

We performed a systematic literature review to identify articles assessing the treatment burden experienced by patients and caregivers to inform the feasibility of developing a quality indicator in this area for home-based medical care. We found no guidelines for healthcare professionals on when to assess for treatment burden and identified no one standardized assessment method. Qualitative data outlined the complexity of treatment burden as not just the burden of using a specific treatment, but all the adaptations and changes that need to be made to an individual’s daily life in order to successfully use a particular treatment. Very little data about caregiver treatment burden were identified.

Many instruments are available to assess treatment burden. Little or no work has been done to assess or compare the performance properties of the different instruments, so deciding which one to use is largely dependent on the number of comorbid conditions, the nature of the conditions and the time available for administration. Most currently available tools are disease-specific but have the potential to be adapted to other disease states, such as the Treatment Well-Being component of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). As the majority of older adults now live with more than one condition [ 60 ] finding a useful tool to assess the burden of treatment in those living with multiple chronic conditions such as the Multimorbidity Treatment Burden Questionnaire [ 50 ] becomes increasingly important.

Surrogate measures of treatment burden, such as polypharmacy or medication regimen complexity are easier to extract from medical records but only capture one aspect of medication burden and therefore may be less useful to assess overall treatment burden. For example, a person with newly diagnosed hypertension has to manage not only possible polypharmacy, but what medication to take and when, side effects of the medication, follow-up monitoring and healthcare visits, insurance paperwork, lifestyle and dietary changes as well as the challenge of finding time to incorporate these changes into their already busy life. The burden only increases as the number and complexity of conditions increases and can make adherence challenging. For people with multiple chronic conditions, this is particularly important, and assessments of the multiple domains of treatment burden are vital. Although instruments such as PETS provide a very detailed assessment, they are time consuming to complete. A simple tool that is quick to administer such as the NHATS measure or the MTBQ may serve as an ideal screen to identify treatment burden. A screening question such as those used in the qualitative interviews or the ICAN Discussion Aid which is designed to take more than three minutes to administer, if positive could be followed by a more detailed assessment using the TBQ, MTBQ or the PETS.

Although most patients and healthcare providers are aware of treatment burden, the lack of a simple method to measure it in the clinical setting may lead to a lack of focus on this important aspect of patient centered care. Healthcare providers need to identify patients burdened by their treatment and engage in approaches to ameliorate it. One approach described in the literature is to engage in minimally disruptive medicine by tailoring treatment regimens to the realities of the daily lives of patients and relevant patient goals [ 10 ]. Patients also need education to encourage them to acknowledge their burden and talk to their provider about what can be done to reduce burden and help foster adherence.

Despite the extensive literature on caregiving burden relatively little information was available about treatment burden experienced by caregivers [ 7 , 22 , 25 , 56 ]. Consumer health organization representatives pointed to the frustration and distress treatment burden causes for caregivers. This is especially true of caregivers of older adults with multiple chronic conditions, dementia or serious illness where social isolation, self-neglect, lack of support and marginalization are frequently experienced. Approximately 43 million Americans provide some type of ongoing, unpaid assistance to a family member or friend with a chronic illness or disability [ 61 ] with an estimated economic value of $450 billion [ 62 ]. Clearly, caregivers carry a significant burden related to the treatment of their family members which healthcare providers and society need to urgently acknowledge and address.

Strengths of this work include the systematic and comprehensive nature of the literature review that included both the peer-reviewed and grey literature and review of both quantitative and qualitative methods for assessing treatment burden. The limitations of our review largely reflect the shortcomings of the field and the lack of standardized tools and measures of treatment burden. The possibility that our search terms and multiple overlapping searches of both the peer-reviewed and grey literature failed to identify a relevant paper or source of information is low but remains a possibility especially as many authors refer to disease burden and treatment burden interchangeably. We chose to include both qualitative and quantitative studies in our review. We acknowledge the potential for qualitative studies to introduce bias by reporting on specific populations that may not be generalizable, however, we feel that they are under-utilized in systematic reviews and in this review are essential to illustrate the breadth of experiences and complexity of treatment burden [ 63 ].

Conclusions

The burden of treatment for chronic conditions is a complex and significant issue for both patients and their caregivers. The predicted growth of the older population over the next few decades will increase the number of people living with multiple chronic conditions. Assessment tools for treatment burden need to be standardized and utilized and appropriate measures developed for different care settings including home care. Patients and caregivers need education in this critical area to help them advocate for care aligned with their individual goals and preferences. Physicians and the healthcare system need to work together to identify patients burdened by their treatment and develop individualized plans in partnership with patients and their families to address the burden.

Additional file

Additional file 1: Details of population studied and instruments used to assess treatment burden. (DOCX 19 kb)

Abbreviations

Cystic Fibrosis Questionnaire-Revised

The Cumulative Index to Nursing & Allied Health

Chronic Obstructive Pulmonary Disease

Health Care Task Difficulty

Instrument for Patient Capacity Assessment

Medical Subject Headlines used for indexing articles in PubMed

Multimorbidity Treatment Burden Questionnaire

National Health and Aging Trends Study

National Library of Medicine

Patient Experience with Treatment and Self-management

Doctor of Philosophy

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Quality of Life-Bronchiectasis

Treatment Burden Questionnaire

Willingness to Accept Life-Sustaining Treatment

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgements

We would like to thank our clinical informationist, Ms. Carrie Price, for her invaluable advice and assistance with the literature search.

Authors’ contributions

Study conception and design: OCS, BL, CSR, SKG, DS, CMB. Acquisition of data: OCS, LL. Analysis and interpretation of data: OCS, RF, BL, CSR, LL, CMB. Drafting of manuscript: OCS, BL, CSR, LL, CMB. Critical revision: OCS, BL, CSR, SKG, DS, RF, CMB. All authors read and approved the final version of the manuscript.

Funding

This study was funded by the Commonwealth Fund. The funding source had no role in the design of the study; collection, analysis, and interpretation of the data; and preparation of the manuscript. Dr. Boyd's time was supported by a K24 award from the National Institutes of Health.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1. Lochner KA Cox CS Prevalence of multiple chronic conditions among Medicare beneficiaries, United States, 2010 Prev Chronic Dis 2013 10 E61 10.5888/pcd10.120137 23618541 PMC3652723

2. Holman H Lorig K Patients as partners in managing chronic disease. Partnership is a prerequisite for effective and efficient health care BMJ. 2000 320 526 527 10.1136/bmj.320.7234.526 10688539 PMC1117581

3. Eton DT Ramalho de Oliveira D Egginton JS Ridgeway JL Odell L May CR Building a measurement framework of burden of treatment in complex patients with chronic conditions: a qualitative study Patient Relat Outcome Meas 2012 3 39 49 10.2147/PROM.S34681 23185121 PMC3506008

4. Mercer S Salisbury C Fortin M ABC of multimorbidity 2014 Chichester, West Sussex Wiley Blackwell/BMJ/Books

5. Vijan S Hayward RA Ronis DL Hofer TP Brief report: the burden of diabetes therapy: implications for the design of effective patient-centered treatment regimens J Gen Intern Med 2005 20 479 482 10.1111/j.1525-1497.2005.0117.x 15963177 PMC1490106

6. Jeon YH Jowsey T Yen L Glasgow NJ Essue B Kljakovic M Achieving a balanced life in the face of chronic illness Aust J Prim Health 2010 16 66 74 10.1071/PY09039 21133301

7. Giovannetti ER Wolff JL Xue QL Weiss CO Leff B Boult C Difficulty assisting with health care tasks among caregivers of multimorbid older adults J Gen Intern Med 2012 27 1 37 44 10.1007/s11606-011-1831-5 21874385 PMC3250537

8. Wolff JL Spillman BC Freedman VA Kasper JD A National Profile of family and unpaid caregivers who assist older adults with health care activities JAMA Intern Med 2016 176 3 372 379 10.1001/jamainternmed.2015.7664 26882031 PMC4802361

9. McCullough AR Tunney MM Stuart Elborn J Bradley JM Hughes CM Predictors of adherence to treatment in bronchiectasis Respir Med 2015 109 7 838 845 10.1016/j.rmed.2015.04.011 25959236

10. May C Montori VM Mair FS We need minimally disruptive medicine BMJ. 2009 339 b2803 10.1136/bmj.b2803 19671932

11. Tran VT Montori VM Eton DT Baruch D Falissard B Ravaud P Development and description of measurement properties of an instrument to assess treatment burden among patients with multiple chronic conditions BMC Med 2012 10 68 10.1186/1741-7015-10-68 22762722 PMC3402984

12. Man MS Chaplin K Mann C Bower P Brookes S Fitzpatrick B Improving the management of multimorbidity in general practice: protocol of a cluster randomised controlled trial (the 3D study) BMJ Open 2016 6 4 e011261 10.1136/bmjopen-2016-011261 27113241 PMC4854003

13. Gallacher K Jani B Morrison D Macdonald S Blane D Erwin P Qualitative systematic reviews of treatment burden in stroke, heart failure and diabetes - methodological challenges and solutions BMC Med Res Methodol 2013 13 10 10.1186/1471-2288-13-10 23356353 PMC3568050

14. Moher D Liberati A Tetzlaff J Altman DG The PRISMA Group Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement PLoS Med 2009 6 7 e1000097 10.1371/journal.pmed1000097 19621072 PMC2707599

15. Fathi R Sheehan OC Garrigues SK Saliba D Leff B Ritchie CS Development of an Interdisciplinary Team Communication Framework and Quality Metrics for Home-Based Medical Care Practices J Am Med Dir Assoc 2016 17 8 725 729 10.1016/j.jamda.2016.03.018 27217093

16. Sheehan OC Ritchie CS Fathi R Garrigues SK Saliba D Leff B Development of Quality Indicators to Address Abuse and Neglect in Home-Based Primary Care and Palliative Care J Am Geriatr Soc 2016 64 12 2577 2584 10.1111/jgs.14365 27787878

17. Gallacher K Morrison D Jani B Macdonald S May CR Montori VM Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research PLoS Med 2013 10 e1001473 10.1371/journal.pmed.1001473 23824703 PMC3692487

18. Jani B Blane D Browne S Montori V May C Shippee N Identifying treatment burden as an important concept for end of life care in those with advanced heart failure Curr Opin Support Palliat Care 2013 7 1 3 7 10.1097/SPC.0b013e32835c071f 23196381

19. Lippiett KA Richardson A Myall M Cummings A May CR Patients and informal caregivers’ experiences of burden of treatment in lung cancer and chronic obstructive pulmonary disease (COPD): a systematic review and synthesis of qualitative research BMJ Open 2019 9 20 e020515 10.1136/bmjopen-2017-020515 30813114 PMC6377510

20. Rosbach M Andersen JS Patient-experienced burden of treatment in patients with multimorbidity – a systematic review of qualitative data PLoS One 2017 12 6 e0179916 10.1371/journal.pone.0179916 28644877 PMC5482482

21. Gallacher K May CR Montori VM Mair FS Understanding patients' experiences of treatment burden in chronic heart failure using normalization process theory Ann Fam Med 2011 9 3 235 243 10.1370/afm.1249 21555751 PMC3090432

22. Sav A McMillan SS Kelly F Kendall E Whitty JA King MA Treatment burden among people with chronic illness: what are consumer health organizations saying? Chronic Illn 2013 9 3 220 232 10.1177/1742395312463411 23093542

23. Boyle J Vukicevic M Koklanis K Itsiopoulos C Rees G Expeirences of patients undergoing repeated intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration Psychol Health Med 2018 23 2 127 140 10.1080/13548506.2016.1274040 28064517

24. Ridgeway JL Egginton JS Tiedje K Linzer M Boehm D Poplau S Factors that lessen the burden of treatment in complex patients with chronic conditions: a qualitative study Patient Prefer Adherence 2014 8 339 351 10.2147/PPA.S58014 24672228 PMC3964167

25. Sav A Kendall E McMillan SS Kelly F Whitty JA King MA 'You say treatment, I say hard work': treatment burden among people with chronic illness and their carers in Australia Health Soc Care Community 2013 21 6 665 674 10.1111/hsc.12052 23701664

26. Boehmer KR Hargraves IG Allen SV Matthews MR Maher C Montori VM Meaningful conversations in living with and treating chronic conditions: development of the ICAN discussion aid BMC Health Serv Res 2016 16 514 10.1186/s12913-016-1742-6 27663302 PMC5034671

27. Harb N Foster JM Dobler CC Patient-perceived treatment burden of chronic obstructive pulmonary disease Int J Chron Obstruct Pulmon Dis 2017 12 1641 1652 10.2147/COPD.S130353 28615937 PMC5459974

28. Fried TR Bradley EH Towle VR Assessment of patient preferences: integrating treatments and outcomes J Gerontol B Psychol Sci Soc Sci 2002 57 6 S348 S354 10.1093/geronb/57.6.S348 12426443

29. Fried TR Bradley EH What matters to seriously ill older persons making end-of-life treatment decisions?: a qualitative study J Palliat Med 2003 6 2 237 244 10.1089/109662103764978489 12854940

30. Hyland Michael E. Whalley Ben Jones Rupert C. Masoli Matthew A qualitative study of the impact of severe asthma and its treatment showing that treatment burden is neglected in existing asthma assessment scales Quality of Life Research 2014 24 3 631 639 10.1007/s11136-014-0801-x 25201169

31. Jordan S Philpin S Warring J Cheung WY Williams J Percutaneous endoscopic gastrostomies: the burden of treatment from a patient perspective J Adv Nurs 2006 56 3 270 281 10.1111/j.1365-2648.2006.04006.x 17042806

32. Gallacher KI May CR Langhorne P Mair FS A conceptual model of treatment burden and patient capacity in stroke BMC Fam Pract 2018 19 1 9 10.1186/s12875-017-0691-4 29316892 PMC5759246

33. Baz R Lin HM Hui AM Harvey RD Colson K Gallop K Development of a conceptual model to illustrate the impact of multiple myeloma and its treatment on health-related quality of life Support Care Cancer 2015 23 9 2789 2797 10.1007/s00520-015-2644-6 25708126

34. Fried TR Van Ness PH Byers AL Towle VR O’Leary JR Dubin JA Changes in preferences for life-sustaining treatment among older persons with advanced illness J Gen Intern Med 2007 22 4 495 501 10.1007/s11606-007-0104-9 17372799 PMC1839865

35. Quittner AL O'Donnell AE Salathe MA Lewis SA Montgomery AB O’Riordan TG Quality of life questionnaire-bronchiectasis: final psychometric analyses and determination of minimal important difference scores Thorax. 2015 70 1 12 20 10.1136/thoraxjnl-2014-205918 25323621

36. Blome C Simianer S Purwins S Laass A Rustenbach SJ Schaefer I Time needed for treatment is the major predictor of quality of life in psoriasis Dermatology. 2010 221 2 154 159 10.1159/000313825 20558972

37. Ishii Hitoshi Shin Hiroki Tosaki Takahiro Haga Tatsuya Nakajima Yoshiki Shiraiwa Toshihiko Watanabe Nobuaki Koizumi Miyuki Nakajima Hiroki Okada Sadanori Mashitani Tsuyoshi Mohri Takako Akai Yasuhiro Reproducibility and Validity of a Questionnaire Measuring Treatment Burden on Patients with Type 2 Diabetes: Diabetic Treatment Burden Questionnaire (DTBQ) Diabetes Therapy 2018 9 3 1001 1019 10.1007/s13300-018-0414-4 29600503 PMC5984917

38. Sawicki GS Sellers DE Robinson WM High treatment burden in adults with cystic fibrosis: challenges to disease self-management J Cyst Fibros 2009 8 2 91 96 10.1016/j.jcf.2008.09.007 18952504 PMC2680350

39. Bolinger R. Comparing the effectiveness of pelvic floor muscle training and acupuncture for the treatment of urinary incontinence and the impact on health-related quality of life for non-homebound women > 50 years of age: a secondary analysis. 2012. University Pittsburgh (online). Available at: d-scholarship.pitt.edu/id/eprint/13610. Accessed September 12, 2018.

40. Leung E Warde P Jewett M Panzarella T O’Malley M Sweet J Treatment burden in stage I seminoma: a comparison of surveillance and adjuvant radiation therapy BJU Int 2013 112 8 1088 1095 10.1111/bju.12330 23937685

41. Presley CJ Soulos PR Tinetti M Montori VM Yu JB Gross CP Treatment burden of Medicare beneficiaries with stage I non-small-cell lung Cancer J Oncol Pract 2017 13 2 e98 e107 10.1200/JOP.2016.014100 27997301 PMC5659117

42. Gallacher KI Batty GD McLean G Mercer SW Guthrie B May CR Stroke, multimorbidity and polypharmacy in a nationally representative sample of 1,424,378 patients in Scotland: implications for treatment burden BMC Med 2014 12 151 10.1186/s12916-014-0151-0 25280748 PMC4220053

43. Grootscholten C Snoek FJ Bijl M van Houwelingen HC Derksen RH Berden JH Health-related quality of life and treatment burden in patients with proliferative lupus nephritis treated with cyclophosphamide or azathioprine/ methylprednisolone in a randomized controlled trial J Rheumatol 2007 34 8 1699 1707 17659757

44. Shah S Akbari M Vanga R Kelly CP Hansen J Theethira T Patient perception of treatment burden is high in celiac disease compared with other common conditions Am J Gastroenterol 2014 109 9 1304 1311 10.1038/ajg.2014.29 24980880 PMC4159418

45. Bernhard J Zahrieh D Zhang JJ Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer Br J Cancer 2008 98 25 33 10.1038/sj.bjc.6604092 18043579 PMC2359705

46. Tran V-T Harrington M Montori VM Barnes C Wicks P Ravaud P Adaptation and validation of the treatment burden questionnaire (TBQ) in English using an internet platform BMC Med 2014 12 1 109 10.1186/1741-7015-12-109 24989988 PMC4098922

47. Déruaz-Luyet A N'Goran AA Tandjung R Frey P Zeller A Haller DM Multimorbidity in primary care: protocol of a national cross-sectional study in Switzerland BMJ Open 2015 5 e009165 10.1136/bmjopen-2015-009165 26510730 PMC4636659

48. Schreiner N Perazzo J Currie J Daly B Webel A A descriptive, cross-sectional study examining treatment burden in people living with HIV Appl Nurs Res 2019 46 31 36 10.1016/j.apnr.2019.02.009 30853073 PMC6746227

49. Schreiner N Schreiner S Daly B The association between chronic condition symptoms and treatment burden in a skilled nursing population J Gerontol Nurs 2018 44 12 45 52 10.3928/00989134-20181019-01 30484847 PMC6747057

50. Duncan P Murphy M Man MS Chaplin K Gaunt D Salisbury C Development and validation of the multimorbidity treatment burden questionnaire (MTBQ) BMJ Open 2018 8 4 e019413 10.1136/bmjopen-2017-019413 29654011 PMC5900423

51. Eton DT Yost KJ Lai JS Ridgeway JL Egginton JS Rosedahl JK Development and validation of the patient experience with treatment and self-management (PETS): a patient-reported measure of treatment burden Qual Life Res 2017 26 2 489 503 10.1007/s11136-016-1397-0 27566732 PMC5753596

52. Krska J Katusiime B Corlett SA Patient experiences of the burden of using medicines for long-term conditions and factors affecting burden: a cross-sectional survey Health Soc Care Community. 2018 26 6 946 959 10.1111/hsc.12624 30058749

53. Martin W Palazzo Poiraudeau S Development and preliminary psychometrics of the exercise therapy burden questionnaire for patients with chronic conditions Arch Phys Med Rehabil 2017 98 11 2188 2195 10.1016/j.apmr.2017.03.015 28427927

54. Boyd CM Wolff JL Giovannetti E Reider L Weiss C Xue QL Healthcare task difficulty among older adults with multimorbidity Med Care 2014 52 Suppl 3 S118 S125 10.1097/MLR.0b013e3182a977da 24561750 PMC3937858

55. Kasper JD, Freedman VA. National Health and Aging Trends Study User Guide: Rounds 1, 2, 3 4 & 5 Beta Release. Johns Hopkins School of Public Health (online). Available at www.nhats.org . Accessed on September 12, 2018.

56. Wolff JL Boyd CM A look at person-centered and family-centered care among older adults: results from a national survey J Gen Intern Med 2015 30 10 1497 1504 10.1007/s11606-015-3359-6 25933625 PMC4579212

57. Rogers EA Yost KJ Rosedahl J Linzer M Boehm DH Thakur A Validating the patient experience with treatment and self-management (PETS), a patient-reported measure of treatment burden, in people with diabetes Patient Relat Outcome Meas 2017 8 143 156 10.2147/PROM.S140851 29184456 PMC5687778

58. Bernhard J Maibach R Thürlimann B Sessa C Aapro MS Patients’ estimation of overall treatment burden: why not ask the obvious? J Clin Oncol 2002 20 1 65 72 10.1200/JCO.2002.20.1.65 11773155

59. Sav A Whitty JA McMillan SS Kendall E Kelly F King MA Treatment burden and chronic illness: who is at Most risk? Patient. 2016 9 6 559 569 10.1007/s40271-016-0175-y 27142372

60. Anderson GF Herbert R Zeffiro T Johnson N Chronic conditions: making the case for ongoing care 2004 Baltimore, MD Partnership for Solutions

61. National Alliance for Caregiving and AARP Caregiving in the U.S 2009 Washington, DC AARP and NAC

62. Feinberg L Reinhard SC Houser A Choula R Valuing the invaluable: 2011 update: the growing contributions and costs of family caregiving. Insight on the issues (AARP public policy institute) 51 2011 Washington, D.C. AARP Public Policy Institute

63. Dixon-Woods M Fitzpatrick R Roberts K Including qualitative research in systematic reviews: opportunities and problems J Eval Clin Pract 2001 7 2 125 133 10.1046/j.1365-2753.2001.00257.x 11489038

64. Faust MA. The use of social media and the impact of support on the well-being of adult cystic fibrosis patients. (Master’s thesis). 2014. University of South Carolina (online). Available at: https://scholarcommons.sc.edu/etd/2758/ . Accessed 29 July 2019.

65. Campbell JL Kiebert GM Partridge MR Development of the satisfaction with inhaled asthma treatment questionnaire Eur Respir J 2003 22 1 127 134 10.1183/09031936.03.00097503 12882462