Определение концепций физической активности, которые имеют клиническое значение для пациентов и лиц, обеспечивающих уход: систематический обзор качественных исследований.

Summary
What is the current knowledge on the topic?
○ Assessing physical activity (PA) is essential for many aspects of clinical research and practice. Additionally, the U.S. Food and Drug Administration (FDA) strongly encourages identifying health concepts of interest meaningful to patients to be included as outcome assessments in drug development. Major progress has been made in identifying concepts of interest related to mobility. However, there is a need to identify PA‐related concepts that extend beyond existing mobility and walking outcomes, for a broader research and care application of PA measures that matter to patients.
What question did this study address?
○ This study conducted a systematic review and thematic analysis of qualitative research to holistically identify concepts of PA that are meaningful to patients.
What does this study add to our knowledge?
○ To the best of our knowledge, this is the first systematic review of qualitative research to assess health concepts of PA that are meaningful to patients and care providers across multiple therapeutic areas. Our analysis suggests five meaningful aspects of health related to PA: (1) ambulation; (2) balance‐dependent activities; (3) activities needing upper limb function; (4) participation in high‐intensity activities; and (5) bending/changing body positioning. Additionally, thematic synthesis of the data revealed three analytical themes: (1) the perceived relationship between PA and quality of life, (2) the identification of key aspects of PA related to the way functional impairments restrict participation in activities of daily living, and (3) barriers and facilitators for engaging in PA in daily life.
How might this change clinical pharmacology or translational science?
○
PA ‐related health concepts meaningful to patients, as described in this study, provide a foundation for future clinical research, enabling the translation of qualitative research results into quantifiable data collected by means of sensor‐based digital health technologies ( sDHTs )

Summary

What is the current knowledge on the topic?
○ Assessing physical activity (PA) is essential for many aspects of clinical research and practice. Additionally, the U.S. Food and Drug Administration (FDA) strongly encourages identifying health concepts of interest meaningful to patients to be included as outcome assessments in drug development. Major progress has been made in identifying concepts of interest related to mobility. However, there is a need to identify PA‐related concepts that extend beyond existing mobility and walking outcomes, for a broader research and care application of PA measures that matter to patients.
What question did this study address?
○ This study conducted a systematic review and thematic analysis of qualitative research to holistically identify concepts of PA that are meaningful to patients.
What does this study add to our knowledge?
○ To the best of our knowledge, this is the first systematic review of qualitative research to assess health concepts of PA that are meaningful to patients and care providers across multiple therapeutic areas. Our analysis suggests five meaningful aspects of health related to PA: (1) ambulation; (2) balance‐dependent activities; (3) activities needing upper limb function; (4) participation in high‐intensity activities; and (5) bending/changing body positioning. Additionally, thematic synthesis of the data revealed three analytical themes: (1) the perceived relationship between PA and quality of life, (2) the identification of key aspects of PA related to the way functional impairments restrict participation in activities of daily living, and (3) barriers and facilitators for engaging in PA in daily life.
How might this change clinical pharmacology or translational science?
○
PA ‐related health concepts meaningful to patients, as described in this study, provide a foundation for future clinical research, enabling the translation of qualitative research results into quantifiable data collected by means of sensor‐based digital health technologies ( sDHTs )

What is the current knowledge on the topic?
○ Assessing physical activity (PA) is essential for many aspects of clinical research and practice. Additionally, the U.S. Food and Drug Administration (FDA) strongly encourages identifying health concepts of interest meaningful to patients to be included as outcome assessments in drug development. Major progress has been made in identifying concepts of interest related to mobility. However, there is a need to identify PA‐related concepts that extend beyond existing mobility and walking outcomes, for a broader research and care application of PA measures that matter to patients.

Assessing physical activity (PA) is essential for many aspects of clinical research and practice. Additionally, the U.S. Food and Drug Administration (FDA) strongly encourages identifying health concepts of interest meaningful to patients to be included as outcome assessments in drug development. Major progress has been made in identifying concepts of interest related to mobility. However, there is a need to identify PA‐related concepts that extend beyond existing mobility and walking outcomes, for a broader research and care application of PA measures that matter to patients.

What question did this study address?
○ This study conducted a systematic review and thematic analysis of qualitative research to holistically identify concepts of PA that are meaningful to patients.

This study conducted a systematic review and thematic analysis of qualitative research to holistically identify concepts of PA that are meaningful to patients.

What does this study add to our knowledge?
○ To the best of our knowledge, this is the first systematic review of qualitative research to assess health concepts of PA that are meaningful to patients and care providers across multiple therapeutic areas. Our analysis suggests five meaningful aspects of health related to PA: (1) ambulation; (2) balance‐dependent activities; (3) activities needing upper limb function; (4) participation in high‐intensity activities; and (5) bending/changing body positioning. Additionally, thematic synthesis of the data revealed three analytical themes: (1) the perceived relationship between PA and quality of life, (2) the identification of key aspects of PA related to the way functional impairments restrict participation in activities of daily living, and (3) barriers and facilitators for engaging in PA in daily life.

To the best of our knowledge, this is the first systematic review of qualitative research to assess health concepts of PA that are meaningful to patients and care providers across multiple therapeutic areas. Our analysis suggests five meaningful aspects of health related to PA: (1) ambulation; (2) balance‐dependent activities; (3) activities needing upper limb function; (4) participation in high‐intensity activities; and (5) bending/changing body positioning. Additionally, thematic synthesis of the data revealed three analytical themes: (1) the perceived relationship between PA and quality of life, (2) the identification of key aspects of PA related to the way functional impairments restrict participation in activities of daily living, and (3) barriers and facilitators for engaging in PA in daily life.

How might this change clinical pharmacology or translational science?
○
PA ‐related health concepts meaningful to patients, as described in this study, provide a foundation for future clinical research, enabling the translation of qualitative research results into quantifiable data collected by means of sensor‐based digital health technologies ( sDHTs )

PA ‐related health concepts meaningful to patients, as described in this study, provide a foundation for future clinical research, enabling the translation of qualitative research results into quantifiable data collected by means of sensor‐based digital health technologies ( sDHTs )

Introduction

Physical activity (PA) has been defined as “any bodily movement produced by skeletal muscles that results in energy expenditure” and it is an essential component of health and daily functioning (Table  1 ) [ 1 ]. Types and intensity of PA can vary substantially and differences in PA may be related to socio‐demographic conditions, age, gender, and health status. PA can include aerobic or anaerobic, muscle and bone strengthening activities for lower or upper extremities, and movements that require changes in body positioning [ 2 ]. Accurate assessment of PA is important for clinical research, prevention and treatment of a number of health conditions, and population surveillance studies as impairments in PA are linked to reduced quality of life, increased likelihood of chronic disease, and premature death [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ].

TABLE 1 Relevant terminology. Term Definition Physical activity “Any bodily movements produced by skeletal muscles that result in energy expenditure” [ 1 ] Exercise “Is a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness” [ 1 ] Activities of daily living Activities required for everyday living, including eating, bathing, toileting, dressing, getting into or out of a bed or chair, and basic mobility [ 9 ] Instrumental activities of daily living Activities related to independent living, including preparing meals, managing money, shopping for groceries or personal items, and performing housework [ 9 ] Meaningful aspect of health Aspect of a disease that a patient (a) does not want to become worse, (b) wants to improve, or (c) wants to prevent [ 10 , 11 ] Concept of interest Simplified or narrowed element that can be practically measured [ 12 ] Therapeutic area “A knowledge field that focuses on research and development of treatments for diseases and pathologic findings, as well as prevention of conditions that negatively impact the health of an individual.” [ 13 ] Qualitative research A research method to gain a deeper understanding of participants' or groups' beliefs, attitudes, perceptions, processes, and meaning attached to phenomena. Examples of qualitative methods include interviews and focus group discussions [ 14 ] Mixed methods research Research that incorporates both quantitative and qualitative research design [ 15 ] Thematic synthesis An approach defined by Thomas and Harden for analyzing qualitative data for systematic reviews of qualitative studies “Thematic synthesis has three stages: the coding of text ‘line‐by‐line’; the development of ‘descriptive themes’; and the generation of ‘analytical themes’. While the development of descriptive themes remains ‘close’ to the primary studies, the analytical themes represent a stage of interpretation whereby the reviewers ‘go beyond’ the primary studies and generate new interpretive constructs, explanations or hypotheses” [ 16 ] Content validity Refers to the extent to which a measurement tool accurately represents and measures all facets of the concept it is intended to assess

Relevant terminology.

Essential aspects of PA data collection in patients with specific disease conditions for clinical research purposes include measuring aspects of health that are meaningful to patients. Identifying health concepts that patients hope, (1) do not become worse; (2) improve; or (3) are prevented, involves qualitative research approaches, as published by the Food and Drug Administration (FDA) in a series of patient‐focused drug development (PFDD) guidance documents and constitutes an important component of drug development [ 12 , 17 ]. Only once these aspects of health are defined should measurable concepts of interest and clinical outcomes be identified [ 10 ]. Previous qualitative research indicated that mobility is intricately tied to identity, ability to engage in activities, and contextual factors like physical, mental, emotional, and social experiences for ambulatory patients [ 18 ]. However, other types of PA, for example, upper limb mobility or changes in body posture, are less well investigated.

PA data can be collected by means of patient self‐reports (what people perceive they do), assessing exercise capacity (what people can do), and performance (what people choose to do). Self‐report methods are often easiest to administer, but they suffer from recall bias and lack of objectivity—patients often overreport their PA [ 19 , 20 ]. Traditional functional activity/performance tests, aimed at assessing exercise capacity (e.g., the 6‐min walk test, 6MWT), may lack qualitative investigation of meaningfulness and can be burdensome to patients as they require scheduling and traveling to clinical sites, resulting in missing data and inequities in who has access to the assessments [ 21 ]. Moreover, they can be influenced by patient motivation, patient levels of activity or tiredness during the day of the test, study facilitator biases resulting from encouragement during testing, sentinel effects, and learning effects, as evidenced by the 6MWT used as the ‘gold standard’ test for Duchenne's Muscular Dystrophy (DMD) [ 22 ]. Additionally, these tests and other in‐clinic assessments measured at discrete intervals may be insufficient to capture type and intensity of PA, representative of people's activities of daily living (ADL) [ 9 ].

The emergence of DHTs in recent years has provided opportunities for clinicians and researchers to capture patient PA under real‐life conditions [ 23 ]. Continuous or more frequent data collection has been articulated as one of the major benefits of DHT deployment in clinical trials [ 24 ]. Additionally, DHT‐generated data offer complementary evidence to in‐clinic exercise capacity tests and can capture data related to health concepts that are meaningful to patients.

PA has been a major area of DHT‐based innovation in clinical research, as many parameters of PA can be assessed by body‐worn sensors coupled with data processing algorithms, sometimes referred to as sensor‐based DHTs (sDHTs) [ 25 ]. They can provide valuable objective data on people's PA in remote settings with low burden on participants. For example, the Mobilise‐D initiative under the auspices of European Innovative Medicines Initiative (IMI) has made great progress in defining measures of real‐world walking, linking them to patients' experiences and translating them into device agnostic, wearable sDHT measures [ 18 , 26 , 27 ]. While these achievements greatly advance our knowledge of qualitative and quantitative research on walking, this work is limited only to a single concept of PA (i.e., walking) across five therapeutic areas (TA) that may be more broadly affected by gait or other movement impairments that impact ADL [ 28 ].

Taking a more holistic approach and identifying multiple health concepts of PA that may be meaningful to patients across a diverse sample of TAs has not yet been done. Such information could further augment our knowledge and facilitate the implementation of more meaningful PA ascertainment measures in clinical research. Translating the results of qualitative research into measures that can reproducibly quantify PA requires identifying common health concepts across disease indications to inform the development of a core set of measures of PA that can be assessed by means of DHTs and other methods. To ground measures in patient‐focused research, in this study, we conducted a systematic review and thematic analysis of qualitative research to identify concepts of PA that are meaningful to patients.

Methods

Selection of Therapeutic Area Sample

To represent the variety of ways PA is relevant across TAs, our sample of diseases for this review includes, Parkinson's disease (PD), multiple sclerosis (MS), chronic obstructive pulmonary disease (COPD), cancer, DMD, chronic heart failure (CHF), sickle cell disease (SCD), osteoarthritis (OA), and sarcopenia. A workshop and rounds of decision‐making by multi‐stakeholder groups representing the pharmaceutical and DHT developer industries, patient advocacy groups, physical activity specialists, and clinical measurement scientists were conducted to narrow down the selected TAs. These conditions cover a breadth of indications across neuromuscular, respiratory, cardiovascular, hematological, and joint disorders, allowing for identification of PA concepts relevant to a broad range of conditions with some similar symptoms. These TAs were selected for this qualitative systematic review based on a matrix considering disease prevalence, number of registered clinical trials in disease areas already using digital endpoints for PA according to the Digital Medicine Society's Library of Digital Endpoints, and the degree of existing qualitative studies in the literature exploring PA perspectives of patients and care providers.

Studies that were assessed included peer‐reviewed articles utilizing qualitative or mixed method research methods, published within the previous 20 years. This protocol was pre‐registered on PROSPERO (CRD42023416708).

Search Strategy

Original peer‐reviewed articles published in multiple language journals were obtained from comprehensive searches of several electronic bibliographic databases: PubMed, Embase, Web of Science Core Collection, Scopus, and Cochrane. A Medical Education Librarian at Vanderbilt University was consulted to identify databases that were most likely to produce relevant results and refine key search terms.

The first step in the process of source selection was an initial limited search of two of the above databases (Embase and PubMed) by a reviewer (BC). This initial search was followed by an analysis of the words contained in the title and abstract of the reviewed papers and of the index terms used to describe the articles. Using all identified keywords and subject terms, an extensive search was then constructed and run across all included databases.

Study Selection

The relevant studies for the systematic review were selected using a standardized method. In the initial selection process, two reviewers (CT, BC) screened study titles and abstracts against the eligibility criteria to determine whether articles were relevant for further screening (Table  2 ). The primary studies cited in review articles were also assessed for eligibility. The articles selected for full‐text review were read by the two reviewers and screened against the eligibility criteria. During the screening and selection process, disagreements between the two reviewers were resolved through discussion until consensus was achieved.

TABLE 2 Eligibility criteria for selecting peer‐reviewed articles to include in the systematic review. Inclusion Exclusion
Peer‐reviewed research articles Perspectives of populations from selected therapeutic areas, including those living with Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, cancer, Duchenne muscular dystrophy, chronic heart failure, sickle cell disease, osteoarthritis, and sarcopenia. Cancers included in this systematic review will be: breast, lung, colorectal, prostate, cervical, thyroid, non‐hodgkin lymphoma, leukemia, kidney, and uterine cancers Perspectives of health care professionals of patients living with the diseases indicated above, including but not limited to, their neurologists, family doctors, nurses, physical therapists, and other allied health professionals Studies that utilize qualitative research methods or a mixed‐methods research design Studies published in multiple languages. Systematic reviews of qualitative research Studies published within the last 20 years

Articles that are not peer‐reviewed Gray literature Intervention/clinical trial studies without qualitative data collected before the intervention Studies that do not utilize qualitative research methods or a mixed‐methods research design Animal research

Eligibility criteria for selecting peer‐reviewed articles to include in the systematic review.

Peer‐reviewed research articles

Perspectives of populations from selected therapeutic areas, including those living with Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, cancer, Duchenne muscular dystrophy, chronic heart failure, sickle cell disease, osteoarthritis, and sarcopenia. Cancers included in this systematic review will be: breast, lung, colorectal, prostate, cervical, thyroid, non‐hodgkin lymphoma, leukemia, kidney, and uterine cancers

Perspectives of health care professionals of patients living with the diseases indicated above, including but not limited to, their neurologists, family doctors, nurses, physical therapists, and other allied health professionals

Studies that utilize qualitative research methods or a mixed‐methods research design

Studies published in multiple languages.

Systematic reviews of qualitative research

Studies published within the last 20 years

Articles that are not peer‐reviewed

Gray literature

Intervention/clinical trial studies without qualitative data collected before the intervention

Studies that do not utilize qualitative research methods or a mixed‐methods research design

Animal research

Data Extraction

Data was extracted by the two reviewers using a standard framework based on the UK National Institute for Health and Care Excellence (NICE) universal template, which included details such as the type of study, participant characteristics, study aims, context, sampling methods, data collection and analysis methods, and findings [ 29 ].

Following Thomas and Harden's approach of thematic synthesis for reviews of qualitative studies, all text under ‘results’ or ‘findings’ of the article, as well as any results reported in the abstract, was treated as data extracted under “findings.” [ 16 ] This includes direct participant quotes and primary interpretations of results.

A risk of bias assessment was conducted during data extraction to describe the quality of studies being included in the synthesis, using the Critical Appraisal Skills Programme (CASP) checklist adapted for qualitative research [ 30 ].

Data Synthesis

Using the thematic synthesis approach outlined by Thomas and Harden, we conducted “line by line” coding of the results section of included articles and then generated descriptive themes, followed by identification of analytical themes organized into meaningful aspects of health and contextual factors influencing the health concepts. An iterative approach (both deductive and inductive methods) was used to develop the coding manual. Initial codes were identified based on the International Classification of Functioning, Disability, and Health (ICF) framework and other terms to help identify meaningful aspects of PA and the context of those concepts, as indicated by our research questions [ 31 ]. We then conducted an initial reading of five included studies (across therapeutic areas) and refined the codes, before two researchers reviewed all the selected articles with the final coding manual, using Atlas.ti Web (version 7.7.1) for qualitative analysis. We had multiple rounds of discussion on the observed code patterns and themes among the authors with expertise in PA and measurement science (AH, AMH, EI, KR, SA, CD, JD, and ACF). We then synthesized findings to generate descriptive and analytical themes that emerged regarding the aspects of PA that patients identified as meaningful to them, their related concepts of interest, and relevant contextual factors (Figure  1 ).

Organization of codes, descriptive themes, and analytical themes. This diagram represents the grouping of qualitative codes, the identification of themes, and the relationship of themes to one another. The content in the black dash‐lined rectangles describes the qualitative codes that were organized to describe the descriptive themes, represented by the black solid rectangles. As outlined in Thomas and Harden's approach for thematic synthesis in systematic reviews of qualitative studies, we defined grouped analytical themes represented in blue circles and their associated sub‐themes in the blue dash‐lined rectangles. Black arrows define the direction of a predictive relationship towards a descriptive theme, whereas blue dash‐lined arrows define the direction of a predictive relationship towards an analytical theme.

Results

Search Results

Our initial search of the databases on March 27, 2023, yielded 5228 articles. Following the removal of duplicates and abstract screening, 165 articles were retrieved for full‐text review. Sixty articles did not meet the eligibility criteria, and ultimately, 105 articles were included (Figure  2 ).

PRISMA flow diagram. This figure displays the flow of identification, selection, and inclusion of articles eligible for this systematic review. A total of 5228 articles were initially identified after a search in PubMed, Embase, Web of Science Core Collection, Scopus, and Cochrane. After duplicates were removed, 3616 articles were screened and 165 articles were assessed for eligibility. After independent full‐text review from 2 reviewers, 105 studies were ultimately included. Reasons for exclusion are included in the right column.

Description of Articles Included

Among the 105 articles included, forty studies were conducted in North America, thirty‐eight in Europe, fifteen in the Western Pacific region, and seven in the Eastern Mediterranean (Table  3 ). No articles conducted studies in countries from Africa. All TAs of interest were represented in the eligible studies, with CHF, cancer, and COPD representing the majority (64%) of included studies. Ninety‐three studies included perspectives from patients, and the qualitative methods used for most studies included in‐depth interviews ( n  = 76), followed by focus group discussions ( n  = 18), other qualitative techniques ( n  = 5), both interviews and focus groups ( n  = 4), and mixed methods approaches ( n  = 3).

TABLE 3 Description of articles.
n
Percentage
Region


a


Eastern Mediterranean 7 6.7 South‐East Asia 2 1.9 North America 40 38.1 Central and South America 1 1.0 Western Pacific 15 14.3 Africa 0 0.0 Europe 38 36.2 Multi‐region 2 1.9
Therapeutic area
Chronic heart failure (CHF) 26 24.8 Cancer 25 23.8 Chronic obstructive pulmonary disease (COPD) 15 14.3 Multiple sclerosis (MS) 13 12.4 Osteoarthritis (OA) 11 10.5 Parkinson's disease (PD) 10 9.5 Sarcopenia 3 2.9 Duchenne's muscular dystrophy (DMD) 2 1.9
Stakeholder
Patient 90 85.7 Care provider 3 2.9 Both 12 11.4
Qualitative type


b


In‐depth interviews (IDI) 76 72.4 Focus group discussions (FGD) 18 17.1 Mixed methods 3 2.9 Other 4 3.8 IDI and FGD 4 3.8
a
Region definitions are based on World Health Organization regional offices, with the exception of separating ‘North America’ (US, Canada, and Mexico) and ‘Central and South America’ (other countries under the Americas regional office).
b
Qualitative type describes the qualitative methods used in the articles included. ‘Other’ refers to qualitative methods which are not in‐depth interviews, focus group discussions, or mixed methods. Examples of approaches categorized with ‘Other’ include qualitative analysis of open text survey questions and patient logs.

Description of articles.

Region definitions are based on World Health Organization regional offices, with the exception of separating ‘North America’ (US, Canada, and Mexico) and ‘Central and South America’ (other countries under the Americas regional office).

Qualitative type describes the qualitative methods used in the articles included. ‘Other’ refers to qualitative methods which are not in‐depth interviews, focus group discussions, or mixed methods. Examples of approaches categorized with ‘Other’ include qualitative analysis of open text survey questions and patient logs.

Qualitative Appraisal

There was a range of quality represented in the included studies. Among the 105 articles, only 38 studies reported having considered the relationship between the researchers and participants, and 51 studies described the use of rigorous qualitative methods of analysis [ 30 ].

Findings of Synthesis

Thematic synthesis of the data revealed three analytical themes: (1) the perceived relationship between PA and quality of life, (2) the identification of key aspects of PA that are most meaningful to patients, and (3) barriers and facilitators for engaging in PA in ADL. Figure  1 outlines the descriptive themes and analytical themes that emerged regarding the meaningful aspects of PA and relevant contextual factors.

Physical Activity to Maintain Independence Is a Key Factor for Quality of Life

Patients identified themes of independence as being tied to their physical activity, which emerged as an essential component related to their perceived self‐worth and quality of life. Patients reported wanting to improve or maintain function to freely take care of themselves, do chores, and move around in the community to engage in pleasurable or enjoyable activities, such as socializing, playing sports, and volunteering [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. You lose the freedom to move in the way that you would like to. That must be the biggest freedom that you have, to be able to go where you like. (person with PD)

Quality of life, for me, is being able to walk on the beach and climbing stairs effortlessly and being able to walk. (person with OA)

I been very active my whole life just about. Marines, I always played basketball, football. tennis, racketball, I mean my quality of life [now] has dropped down to zero. (person with COPD)

You lose the freedom to move in the way that you would like to. That must be the biggest freedom that you have, to be able to go where you like. (person with PD)

Quality of life, for me, is being able to walk on the beach and climbing stairs effortlessly and being able to walk. (person with OA)

I been very active my whole life just about. Marines, I always played basketball, football. tennis, racketball, I mean my quality of life [now] has dropped down to zero. (person with COPD)

Participation in Activities of Daily Living Is the Most Meaningful Aspect of Physical Activity

The aspects of PA that patients describe as most meaningful were related to the way functional impairments restricted participation in ADL, such as engaging in self‐care behavior; completing domestic tasks; engaging in community, social, and civic activities; and maintaining personal relationships. Specifically, these concepts of PA represented analytical themes summarized into “meaningful aspects of health” and include activities dependent on ambulation, balance‐dependent activities, activities needing upper limb function, bending/changing body positions, and participating in activities of different intensities (see Table  4 and Table  S1 for contributions from each included study to the synthesized meaningful aspects of health (MAH) themes).

TABLE 4 Identified meaningful aspects of health with illustrative quotes. Analytical themes: meaningful aspects of physical activity Descriptive themes with ICF codes & examples provided by patients Illustrative quotes Ambulation Community & leisure activities
– Walking around a shop – Walking in a garden – Walking along a beach

“Quality of life, for me, is being able to walk on the beach and climbing stairs effortlessly and being able to walk.” (person with osteoarthritis) [ 34 ]
“I, you know, could not leave, go places because I couldn't walk well and I had to cancel some things that I was going to do and I felt very self‐conscious about my barely walking and just ended up staying home. I was concerned about tripping, falling.” (person with multiple sclerosis) [ 44 ]
Interpersonal & relationships
– Walking with a friend – Walking to social events
“I used to go walking three times a week. My friend across the street asked me to go walking. So I told her that morning, ‘I can't walk as fast as you. Just go on. Don't wait on me.’ Then I got to a place where I couldn't walk anymore.” (person with chronic heart failure) [ 45 ] Domestic activities
– Walking in the home to do chores – Walking up stairs
“I can't go shopping. Now that everything is online, I just shop online. […] Because, I can't walk for most periods of time.” (Patient 14, 64 years) “I try to grocery shop. […] there are so many times when I actually have to go sit down, because I can't make it all the way through the shop.” (Patient 26, 49 years) (people with chronic heart failure) [ 46 ] Balance‐dependent activities Community & leisure activities
– Walking outside without falling – Having balance to play sports

“And because I feel short of breath so often, I am afraid to do certain things. I also feel very dizzy and wobbly, which makes me feel insecure.” (person with chronic heart failure) [ 47 ]
“…my father was, he was training people to be ice skating. And I said ‘oh let's go!’ And then I realized I can't go to this because my whole leg, it's, it's going to fall down … I felt scared.” (person with multiple sclerosis) [ 48 ]
Self‐care activities
– Getting out of bed without falling – Stability while getting dressed – Standing in the bathtub

“I now have one of those shower stools, then it's alright (showering). Because I can't stand in the bathtub and shower—I'd fall down.” (person with multiple sclerosis) [ 45 ]
“Once I fell when I was climbing up some stairs. I just laid there and couldn't get up. I moved very slowly. I had to move slowly. And now, because I'm scared of falling, I move even more slowly.” (person with Parkinson's Disease) [ 49 ]
Domestic activities
– Doing yard and house chores – Squatting to pick up groceries without falling – Going shopping
“‘I guess I'm a bit tentative about shopping, going out. I'm afraid of falling again because if you fall it makes you a little anxious about shopping.” (person with osteoarthritis) [ 50 ] Activities needing upper limb function Community & leisure activities
– Playing upper body‐dependent sports – Volunteering – Lifting a paintbrush

“I don't volunteer in the library anymore because I can't pick up heavy books and put them up on the shelf. Well, I dabbled in needlework and things like that. If I work too long, then my hands cramp up.” (person with sarcopenia) [ 51 ]
“I just wanted to be able to get more of a range with this arm because it meant the end of my golf—if I couldn't swing it all the way up.” … “Obviously, I gave up playing tennis. I gave up playing volleyball. I can't do any of my upper extremity sports. I still ski; I just don't pole‐plant anymore.” (person with breast cancer) [ 52 ]
Self‐care activities
– Lifting a hairbrush – Washing one's hair – Lifting eating utensils

“I also notice that my arms get really, really tired and—well, all of me gets tired, like I can't wash my hair without taking breaks because my arms get tired.” (person with multiple sclerosis) [ 39 ]
Most participants reported reduced strength, particularly in the arms: “My physical strength is gone. I used to be able to lift pretty heavy stuff, and now, it's like, lifting a hairbrush… I'm so tired that it's… difficult.” (person with breast cancer) [ 37 ]
Domestic activities
– Putting dishes in the cupboard – Carrying a laundry basket – Pushing around a vacuum
Upper limb impairments were described as loss of mobility “The arm weakness is a real problem for me because I cannot reach for a lot of things that I would like to reach. It can get frustrating to have somebody help me every time I need to get something.” (person with Duchenne's Muscular Dystrophy) [ 38 ] Participating in activities of different intensities Community & leisure activities
– Playing sports – Enjoying the outdoors – Going on runs – Exercising for health – Traveling and exploring – Helping with chores – Keeping active

“Before this heart attacked me, I could work outside all day and not feel tired at all. I walked and ran fast. I could lift or push heavy stuff without any problem. Climbing the stairs? Not a problem at all. I enjoyed my life outdoors very much. Now, only walking from room to room around the office makes me tired.” (person with chronic heart failure) [ 53 ]
[About social activities] “There are a lot of things I've had to give up, you know. Well playing football…Can't walk along the corridor, never mind run. And as I said, when you go out with your wife and she's carrying two big bags and you're walking along there with nothing, people must say to themselves, ‘Oh look at that man his wife carrying the bags and he's got nothing,’ but at the end of the day they dinnae ken [don't know] what's happening inside you!” (person with chronic obstructive pulmonary disease) [ 54 ]
“I knew I was sitting a lot because I take breaks, I would like to sit less.” (person with multiple sclerosis) [ 55 ]
Being deprived of social activities, such as entertainment, hobbies, traveling, sports and participating in parties had a negative impact on the QOL of some of the participants: “That I cannot walk and exercise much, has made me feel that I lack something.” … and “It makes me upset that I am always at home.” …. A 69‐ ear‐old man said: “I wish I could travel and do sightseeing more frequently, but I cannot.” (person with chronic heart failure) [ 51 ]
Bending/changing body positions Self‐care activities
– Dressing oneself – Cleaning legs/ft
Seemingly easy activities, like washing one's hair (with arms lifted) or bending down to the floor, caused breathlessness and fatigue. “It's hard to bend over like this [down towards the floor]; my entire body quite simply gives out … and I get short of breath, and have difficulties, when I bend over like this.” (person with chronic heart failure) [ 56 ] Domestic activities
– Loading the dishwasher – Making the bed – Picking things up

“[I fear] getting down [to] where I can't live by myself.”… “The vacuum cleaner de‐winded me; sweeping is just as bad. I can't bend over … I can't raise my arms up or I lose my air, so I'm just really a helpless person.” (person with chronic obstructive pulmonary disease) [ 57 ]
“To grab dishes out of the dishwasher, if I keep on doing the bending and standing motion (that's hard).” Participants further explained that reduced ability to squat limits picking up items such as groceries, and the combination of squatting and picking up items may result in balance issues. (person with lung cancer) [ 37 ]

Identified meaningful aspects of health with illustrative quotes.

Walking around a shop

Walking in a garden

Walking along a beach

“Quality of life, for me, is being able to walk on the beach and climbing stairs effortlessly and being able to walk.” (person with osteoarthritis) [ 34 ]

“I, you know, could not leave, go places because I couldn't walk well and I had to cancel some things that I was going to do and I felt very self‐conscious about my barely walking and just ended up staying home. I was concerned about tripping, falling.” (person with multiple sclerosis) [ 44 ]

Walking with a friend

Walking to social events

Walking in the home to do chores

Walking up stairs

Walking outside without falling

Having balance to play sports

“And because I feel short of breath so often, I am afraid to do certain things. I also feel very dizzy and wobbly, which makes me feel insecure.” (person with chronic heart failure) [ 47 ]

“…my father was, he was training people to be ice skating. And I said ‘oh let's go!’ And then I realized I can't go to this because my whole leg, it's, it's going to fall down … I felt scared.” (person with multiple sclerosis) [ 48 ]

Getting out of bed without falling

Stability while getting dressed

Standing in the bathtub

“I now have one of those shower stools, then it's alright (showering). Because I can't stand in the bathtub and shower—I'd fall down.” (person with multiple sclerosis) [ 45 ]

“Once I fell when I was climbing up some stairs. I just laid there and couldn't get up. I moved very slowly. I had to move slowly. And now, because I'm scared of falling, I move even more slowly.” (person with Parkinson's Disease) [ 49 ]

Doing yard and house chores

Squatting to pick up groceries without falling

Going shopping

Playing upper body‐dependent sports

Volunteering

Lifting a paintbrush

“I don't volunteer in the library anymore because I can't pick up heavy books and put them up on the shelf. Well, I dabbled in needlework and things like that. If I work too long, then my hands cramp up.” (person with sarcopenia) [ 51 ]

“I just wanted to be able to get more of a range with this arm because it meant the end of my golf—if I couldn't swing it all the way up.” … “Obviously, I gave up playing tennis. I gave up playing volleyball. I can't do any of my upper extremity sports. I still ski; I just don't pole‐plant anymore.” (person with breast cancer) [ 52 ]

Lifting a hairbrush

Washing one's hair

Lifting eating utensils

“I also notice that my arms get really, really tired and—well, all of me gets tired, like I can't wash my hair without taking breaks because my arms get tired.” (person with multiple sclerosis) [ 39 ]

Most participants reported reduced strength, particularly in the arms: “My physical strength is gone. I used to be able to lift pretty heavy stuff, and now, it's like, lifting a hairbrush… I'm so tired that it's… difficult.” (person with breast cancer) [ 37 ]

Putting dishes in the cupboard

Carrying a laundry basket

Pushing around a vacuum

Playing sports

Enjoying the outdoors

Going on runs

Exercising for health

Traveling and exploring

Helping with chores

Keeping active

“Before this heart attacked me, I could work outside all day and not feel tired at all. I walked and ran fast. I could lift or push heavy stuff without any problem. Climbing the stairs? Not a problem at all. I enjoyed my life outdoors very much. Now, only walking from room to room around the office makes me tired.” (person with chronic heart failure) [ 53 ]

[About social activities] “There are a lot of things I've had to give up, you know. Well playing football…Can't walk along the corridor, never mind run. And as I said, when you go out with your wife and she's carrying two big bags and you're walking along there with nothing, people must say to themselves, ‘Oh look at that man his wife carrying the bags and he's got nothing,’ but at the end of the day they dinnae ken [don't know] what's happening inside you!” (person with chronic obstructive pulmonary disease) [ 54 ]

“I knew I was sitting a lot because I take breaks, I would like to sit less.” (person with multiple sclerosis) [ 55 ]

Being deprived of social activities, such as entertainment, hobbies, traveling, sports and participating in parties had a negative impact on the QOL of some of the participants: “That I cannot walk and exercise much, has made me feel that I lack something.” … and “It makes me upset that I am always at home.” …. A 69‐ ear‐old man said: “I wish I could travel and do sightseeing more frequently, but I cannot.” (person with chronic heart failure) [ 51 ]

Dressing oneself

Cleaning legs/ft

Loading the dishwasher

Making the bed

Picking things up

“[I fear] getting down [to] where I can't live by myself.”… “The vacuum cleaner de‐winded me; sweeping is just as bad. I can't bend over … I can't raise my arms up or I lose my air, so I'm just really a helpless person.” (person with chronic obstructive pulmonary disease) [ 57 ]

“To grab dishes out of the dishwasher, if I keep on doing the bending and standing motion (that's hard).” Participants further explained that reduced ability to squat limits picking up items such as groceries, and the combination of squatting and picking up items may result in balance issues. (person with lung cancer) [ 37 ]

Patients reported that ambulation was a key aspect of PA needed to participate in domestic activities, such as walking from room to room to complete house chores, taking a stroll with friends and family, and walking leisurely in the community. Both the volume of walking and the ability to walk continuously, across different intensities (cadence, speed, stairs), were identified as important elements of ambulation for patients [ 58 ]. I used to go walking three times a week. My friend across the street asked me to go walking. So, I told her that morning, ‘I can't walk as fast as you. Just go on. Don't wait on me.’ Then I got to a place where I couldn't walk anymore. (person with CHF)

I used to go walking three times a week. My friend across the street asked me to go walking. So, I told her that morning, ‘I can't walk as fast as you. Just go on. Don't wait on me.’ Then I got to a place where I couldn't walk anymore. (person with CHF)

Having stability and maintaining balance while moving and stationary were also reported as necessary to independently engage in community activities, complete chores and go shopping, and take care of oneself. Patients also expressed how impaired balance while walking and fear of falling perpetuated feelings of anxiety and self‐consciousness, further preventing participation in everyday activities [ 50 ]. I guess I'm a bit tentative about shopping or going out. I'm afraid of falling again because if you fall it makes you a little anxious about shopping. (person with OA)

I guess I'm a bit tentative about shopping or going out. I'm afraid of falling again because if you fall it makes you a little anxious about shopping. (person with OA)

In addition, impairments in the upper limb function and the ability to bend or change positions were related to limitations in instrumental ADL, including the ability to care for oneself and do household chores. A loss of arm mobility and strength also resulted in limitations for participating in previously enjoyable activities, such as sports and volunteering [ 38 , 57 ]. The arm weakness is a real problem for me because I cannot reach for a lot of things that I would like to reach. It can get frustrating to have somebody help me every time I need to get something. (person with DMD)

“[I fear] getting down [to] where I can't live by myself.”… “The vacuum cleaner de‐winded me; sweeping is just as bad. I can't bend over … I can't raise my arms up or I lose my air, so I'm just really a helpless person.” (person with COPD)

The arm weakness is a real problem for me because I cannot reach for a lot of things that I would like to reach. It can get frustrating to have somebody help me every time I need to get something. (person with DMD)

“[I fear] getting down [to] where I can't live by myself.”… “The vacuum cleaner de‐winded me; sweeping is just as bad. I can't bend over … I can't raise my arms up or I lose my air, so I'm just really a helpless person.” (person with COPD)

Patients also revealed that beyond just having the physical function to move around the home and community, there was a desire to reach varying intensities of activity and a loss experienced from the inability to exercise and improve their physical health [ 59 ]. That I cannot walk and exercise much, has made me feel that I lack something…it makes me upset that I am always at home. (person with CHF)

That I cannot walk and exercise much, has made me feel that I lack something…it makes me upset that I am always at home. (person with CHF)

Personal and Environmental Factors Act as Barriers and Facilitators for Engaging in ADL

Personal and environmental factors were perceived as barriers or enablers to participating in desired daily experiences related to PA. Individual barriers include disease symptoms such as breathlessness, fatigue, pain, and muscle weakness, which limit patients' functions and movement [ 38 , 43 , 46 , 48 , 54 , 55 , 56 , 57 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. Patients also describe feeling fear of consequences from an inability to perform PA adequately and perceived negative attitudes towards their physical ability, leading to internalized feelings of shame and self‐consciousness, which further prevented engagement in life experiences requiring PA [ 35 , 43 , 47 , 48 , 55 , 57 , 61 , 66 , 79 , 86 , 87 , 88 , 89 , 90 , 91 ]. I fell last week because somebody just knocked me over the shoulder and because my stability's not good. So, you can imagine how embarrassed I felt. So that's why I reduced the numbers of times when I go out…' (person with MS)

I am afraid to do certain things. I also feel very dizzy and wobbly, which makes me feel insecure (person with CHF)

I fell last week because somebody just knocked me over the shoulder and because my stability's not good. So, you can imagine how embarrassed I felt. So that's why I reduced the numbers of times when I go out…' (person with MS)

I am afraid to do certain things. I also feel very dizzy and wobbly, which makes me feel insecure (person with CHF)

To contrast, facilitators that encourage participation in PA include personal motivation, walking aids, and social support from family and friends [ 40 , 45 , 48 , 52 , 55 , 56 , 61 , 65 , 66 , 67 , 68 , 80 , 81 , 86 , 89 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. Family has always been a source of support for me to accept the disease and to deal with it. A lot of mornings I would be very tired sitting on my sofa or lying in my bed until my son comes and asks me to go for a walk with him. His encouragement pulls me up…I usually feel much better afterwards. (person with PD)

Family has always been a source of support for me to accept the disease and to deal with it. A lot of mornings I would be very tired sitting on my sofa or lying in my bed until my son comes and asks me to go for a walk with him. His encouragement pulls me up…I usually feel much better afterwards. (person with PD)

Discussion

To our knowledge, this is the first systematic review and thematic analysis of prior qualitative research assessing meaningful aspects of PA for patients and care providers across multiple chronic conditions and beyond just walking measures. More specifically, our data suggest that there are five meaningful aspects of health related to PA: (1) ambulation; (2) balance‐dependent activities; (3) activities needing upper limb function; (4) participation in high‐intensity activities; and (5) bending/changing body positioning. Our study also revealed themes related to the perceived value of PA and factors that influence engagement in PA. In addition, our study reinforces the need for a standardized set of digital measures for PA that are applicable across TAs.

In contrast to traditional in‐lab assessments of PA, sDHTs provide new opportunities to capture PA in daily life, consistent with the applications of PA that are meaningful to patients [ 22 , 23 ]. Previous studies have identified mobility outcomes that can be assessed digitally. The Mobilise‐D study has recognized mobility, specifically walking ability, as a crucial health indicator. Mobilise‐D research focused specifically on digital gait and mobility measures (DMO) development by combining a review with a Delphi‐based approach to achieve consensus on narrative definitions from research, academia, and industry [ 25 ]. That research identified the need for future work to evaluate the relationship between real‐world and clinical assessments, concentrating on five conditions (COPD, PD, MS, proximal femoral fracture (PFF), and CHF). More specifically, Mobilise‐D created a ‘terminological framework’ for six essential terms: walking, purposeful, real‐world, walking bout, walking speed, and turning; providing definitions and context for measurement to guide future validation of a real‐world DMO measurement system.

Our investigation advances the field and is pioneering in its attempt to uncover various health concepts of PA that are meaningful to patients, beyond just walking measures, and across a broader spectrum of TAs. Our findings highlight a number of interrelated analytical themes which can be further refined and translated into more distinctive concepts of interest and subsequently into measurable entities via sDHTs. This enhances our understanding and contributes to the integration of PA measures into clinical research. Furthermore, our analytical approach is ultimately aimed at developing a core set of digital PA measures across a broad spectrum of TAs, derived from meaningful aspects of health and associated concepts of interest.

Overall, our research offers valuable new insights that will equip sponsors with the necessary tools and resources to generate evidence of content validity for PA, which will additionally require further refinement for a specific indication of interest (e.g., via clinical validation) [ 98 ]. The applications of this work also extend to clinical care and public health by laying the foundation for identifying consensus PA measures, which can be monitored to inform patient health status based on changes in PA that matter to patients. Performing this systematic review on a broad range of TAs with considerable symptom overlap contributes to the advancement of the standardization of a core set of PA measures.

To illustrate further clinical applications of this research, Figure  3 outlines measurable concepts of interest derived from meaningful aspects of health, which can be further expanded to identify fit‐for‐purpose measures. We hope that our endeavor will enable sponsors to connect digital clinical measures to patient‐relevant outcomes, thereby demonstrating content validity as sought after by regulatory bodies. For instance, the Bellerophon case study serves as an excellent illustration of how evidence for content validity can lead to the endorsement of moderate to vigorous PA as a primary outcome in patients with fibrotic lung disease, highlighting its significance [ 99 ]. By presenting a conceptual model of relevant and meaningful aspects of PA, we aspire to promote the standardization of already created or newly developed digital measures of PA.

Conceptual model outlining meaningful aspects of health related to physical activity and related measurable concepts of interest. The findings of this systematic review of qualitative studies has enabled the identification of meaningful aspects of health (MAH) related to physical activity, which is an aspect of physical activity that a patient “(a) does not want to become worse, (b) wants to improve, or (c) wants to prevent.” From these MAHs, it is possible to narrow down measurable concepts of interest, which can be used downstream to ultimately define measures or outcomes that are meaningful to patients.

This study has certain limitations. First, while the systematic review was open to non‐English publications, studies from western countries were predominantly represented. This focus may affect the representation of diversity and global applicability of the findings to all humankind, a factor that could be even more pertinent when considering the influence of behavioral and cultural differences on PA. Second, our study was open to bias and lacked generalizability due to being limited by the sample of TAs selected. The TAs included in this study were chosen based on the volume and breadth of qualitative research publications available, potentially leading to an underrepresentation of TAs with fewer qualitative studies and further exacerbating bias towards the abundance of research in these TAs. This is a common challenge for systematic reviews across TAs, as is noted in the FDA's Patient‐Focused Drug Development guidance [ 17 ]. However, this systematic review can form the groundwork for future studies by leveraging and developing further other important TAs not covered in the current investigation. While the results offer a collective overview across TAs, additional research is necessary to generate indication‐specific evidence for content validity.

Future analyses incorporating a broader dataset of chronic conditions should be conducted to determine whether the current findings are consistent and reproducible. Specifically, this research could be of great interest in rare diseases where patients' ability to engage in physical activity is impaired as many of these diseases would benefit from developing novel disease assessment measures and related endpoints. Additionally, these analyses can enhance confidence in common concepts of PA that are broadly meaningful to patients and identify potential nuances specific to individual conditions. Such investigations will advance the field by refining PA measures in clinical research, ultimately supporting the development of drugs and sDHTs that better align with patients' needs and priorities. Moreover, this research can further enhance and augment our knowledge of certain medical conditions and expand it beyond traditional assessments done during clinical visits. The combination of understanding aspects of PA that are meaningful to patients, with objective data collection by means of sDHTs, can provide a more complete, holistic picture of diseases and can be leveraged further to improve both care delivery and clinical research.

Conclusions

This systematic review of qualitative studies reveals, for the first time, the meaningful aspects of PA and contextual factors that promote or limit patient performance of PA in daily life.

This research serves as a foundation to define measures that can be used to support endpoints in clinical trials by facilitating the development of therapeutics that target the improvement of aspects of PA that matter to patients. We also highlight the opportunities to build upon these patient‐focused concepts to define a core set of digital measures of PA that can be standardized and applied broadly in both clinical research and care settings that together will enable innovative and patient‐centered measurement of physical activity.

Author Contributions

C.T., S.A., K.F.R., C.D., and E.S.I. wrote the manuscript; C.T., S.A., K.F.R., C.D., A.C.F., A.L.H., A.M.H.H., J.D., and E.S.I. designed the research; C.T., J.C., and B.X.C. performed the research; and C.T., S.A., J.C., K.F.R., C.D., A.C.F., A.L.H., A.M.H.H., B.X.C., J.D., and E.S.I. analyzed the data.

Conflicts of Interest

C.T. and J.C. are employees of the Digital Medicine Society (DiMe), the sponsor of this study. J.D. is involved in collaborative research contracts with DiMe (not for this study). The other authors are employees of their respective organizations. E.S.I. is a shareholder of her respective organizations. All other authors declared no competing interests for this work.

Supporting information

Data S1