A number of existing researches agree that digitalization would facility firms to launch ambidextrous innovations. Digitalization is not only about technological change, but more importantly, the reshaping of the firms’ knowledge structure and routines to percept and integrate knowledge. Thus, some researchers suggest that whether firms could benefit from digitalization varies across firms and industries, since innovation in different firms and industries relies on differentiated level of cognitive and reasoning of knowledge. However, existing studies mainly focus on exploring the firm-level differences, and leave the industry-level difference underdeveloped. In response, this study integrates knowledge-based view to examine how a firm’s digitalization affects ambidextrous innovation, and further explore the conjoint effect of industrial knowledge bases—the knowledge base of the industry the firm is located in—on the relationship between firm digitalization level and ambidextrous innovation. This study uses Python to conduct text mining of firms’ annual reports, and obtains data of 394 listed companies from the year 2014 to 2020. The empirical results show that digitalization level has positive effect on both exploratory innovation and exploitative innovation, and the effect on exploitative innovation is stronger than on exploratory innovation. Moreover, the moderating effect of industrial knowledge base is significant on “digitalization–exploratory innovation” but not on “digitalization–exploitative innovation” relationship. By doing so, this study refines the research on the relationship between digitalization and firm innovation, and confirms that the usage of digitalization may lead to achieve an ambidextrous situation. This study also provides a theoretical basis for industrial differences of the effectiveness of digitalization, suggesting firms considering industrial characteristics to implement digitalization-assisted innovation practices. According to the Digital China Development Report in 2020, China’s total digital economy has jumped to the second place in the world. As an infrastructure of society, digital technology has a profound impact on people’s production and life. Firms operating in digital economy are faced with ever-changing and highly competitive environment, thus most firms are seeking digital transformation to largely introduce digital technologies into firm production practice . DigitizThe new technological revolution triggered by digital technologies  has not only changed the firms’ cognitive state toward knowledge, management paradigm, and production and operation process of firms, but also changed the innovation model of firms . From thSome studies state that whether firms could benefit from digitalization varies across industries e.g., . Some fiTo sum up, existing studies have largely demonstrated that digitalization may enable firms to take ambidextrous innovations, and pointed out that such effect varies across industries, since innovation in different industries relies on various level of cognitive and reasoning of knowledge. However, little research has been done to explore the industrial difference in such context. This study focuses on two research questions: (1) could digitization enable firms’ ambidextrous innovation? And (2) how such relationships vary across industries? To address these two research questions, this study incorporates knowledge-based view to explore the effect of digitization level on firm ambidextrous innovation, and examine the contingency effect of a crucial industrial level factor—industrial knowledge base. By doing so, this study makes significant contributions to the existing literatures. First, this study deepens our understanding of the effect of digitalization on different innovation types from the knowledge-based view. The empirical results show that digitization level has a positive effect on both exploratory and exploitative innovation, and the impact on exploitative innovation is stronger than that on exploratory innovation. The results indicate that digitization may enable firms to integrate knowledge throughout different operational process to realize exploratory innovation and exploitative innovation at the same time. Second, this study extends the industry level boundary conditions on the effectiveness of digitalization. The findings show the moderating effect of industrial knowledge base on the relationship between digitalization level and firm exploratory innovation but not on the relationship between digitalization level and exploitative innovation, which partly suggesting that the effect of digitization varies in synthetic knowledge-based industries and analytical knowledge-based industries.This paper is organized as follows. The next section presents the relevant literature review and then develop the conceptual model with testable hypotheses. Then the methodology including the data and sampling are described. In the next section, this paper summarizes the results of empirical results, and then concludes the research findings in the following section. The discussion part concludes the theoretical and managerial implications, limitations and future research directions.Faced with high uncertain environment and fierce market competition, innovation is becoming increasingly important for firms’ survival and growth in today’s digital economy . InnovatFirms demonstrating exploratory innovation usually actively seek for radical changes, collect fresh resources and expand aggressively to generate innovations that significantly transfer existing products and services. Such firms are commonly engaged in seeking for new opportunities, including search, discovery, experimentation, risk-taking decisions, and proactive activities . CorrespFirms preferring to exploitative orientation often possess highly refined routines that leverage clearly identified core competitive advantages  and launTo sum up, regarding scarce resources, capabilities and limited attention , firms uA lot of prior literatures on ambidexterity defends the complementarities that exist between the exploratory and exploitative innovation orientations . SpecifiDigitalization involves the usage of digital technology to create value in new ways to boost fundamental firm change . In the Digitalization has led researchers to question increasingly the explanatory powers and utility of existing conceptualizations of innovation . ExistinSome other studies find that effectiveness of digitalization to the performance varies across firms and industries. A number of researches suggest that digital technologies have fundamentally transformed traditional firms and industries . But mosRecently, some studies have begun to pay attention to industry differences and believe that there are significant differences in the impact of digitalization levels on firm innovation across different industries e.g., . The maiIndustrial knowledge base indicates that the basic professional information or knowledge that can be shared and shared among the same type of knowledge creation organizations in the industry, mainly including synthetic knowledge base and analytical knowledge base . SynthetIn sum, industrial knowledge base indicates an industry’s rationale cognition of knowledge. A synthetic knowledge base is primarily about innovation through the generation of new knowledge through scientific research, and analytical knowledge base refers to the understanding and interpretation of characteristics of the  world using natural systems and following scientific laws. The typical differences between two types of industrial knowledge base are presented in the following table see .Existing researches on industrial knowledge base mainly focus on the influence of industrial knowledge base on the construction of regional innovation system and innovation network . In the Innovation is essentially the creation of knowledge, and innovation activities must follow the unique nature and integration of knowledge . ConsideA number of researches base on knowledge management and organizational learning related literatures and offer an integrative framework to explain how and why firms launch innovation . In digiDigitization greatly improves firms’ efficiency and effectiveness through collecting and processing a huge amount of knowledge and data. It can link product design, production, marketing and feedback, make quick responses to market demands, and speed up the pace of innovation of new products ; also, dstatus quo  . In thisFor exploitative innovation, firms may introduce digital technologies to leverage existing strengths, and build on existing business processes to optimize the process, realize mass production to promote delivery capability, and finally improve efficiency . SpecialH1a: Digitization level facilitates exploratory innovation.H1b: Digitization level facilitates exploitative innovation.Innovation is the process of knowledge generation, diffusion and utilization, in which knowledge base plays a key role. Accordingly, the nature of industrial knowledge base affects the development of innovation activities. As mentioned above, industrial knowledge bases are divided into synthetic knowledge bases and analytical knowledge bases, and these two knowledge bases are defined according to the attributes of knowledge creation activities. Synthetic knowledge bases emphasize the application or recombination of existing knowledge. Industries with synthetic knowledge bases are mostly machinery, shipbuilding, computer development, and analytical knowledge bases are new knowledge generated through scientific research, including industries such as biomedicine, life sciences .Industrial knowledge base refers that the firms located in those industries use different methods to integrate and create knowledge . Tacit kSpecifically, firms operating in synthetic knowledge-based industries need to broad their knowledge sources and integrate a large amount of knowledge in the process of innovation activities , and useIn synthetic knowledge-based industries, such as aviation, automotive design, or semiconductor industries, a large amount of knowledge is accumulated and recombined, thus the application of digital technology may improve firms’ big data processing capabilities . That isIn comparation, most of the analytical knowledge-based industries face extremely complex and difficult-to-control technologies . Firms lH2a: Industrial knowledge base moderates the “digitalization level-exploratory innovation” relationship. Compared with the analytical industrial knowledge base, the synthetic industrial knowledge base has a stronger moderating effect on the relationship between digitalization level and firm exploratory innovation.Based on the knowledge-based view, the value of knowledge can be fully utilized when the knowledge base of a firm matches the corresponding technology. Innovations in synthetic knowledge-based industries often involve the use of new methods to improve production efficiency, product quality, or reliability . These iH2b: Industrial knowledge base moderates the “digitalization level-exploitative innovation” relationship. Compared with the analytical industrial knowledge base, the synthetic industrial knowledge base has a stronger moderating effect on the relationship between digitalization level and firm exploitative innovation.This study explores the effects of digitalization and firm ambidextrous innovation, and mainly focuses on the moderating effect of industrial knowledge base. This study uses secondary data to classify the industries to indicate the industrial knowledge bases to test the proposed hypotheses. According to the High-tech Industry Statistical Classification Catalogue issued by the National Bureau of Statistics, the IT industry and communication equipment manufacturing industry are selected as samples with a synthetic knowledge base, and the pharmaceutical manufacturing industry and chemical manufacturing industry are selected as research samples with an analytical knowledge base. This paper selects these four types of industries mainly for the following reasons: firstly, these types of industries started early, with strong technological foundation and innovation capability, and have good stability; It is very different from the core products. In the research, it can highlight the differences between industries and ensure the objectivity and operability of the research. Initially this study obtained a sample data of more than 400 listed companies in the above four industries from 2014 to 2020, and leave 394 sample companies after preliminary screening.According to previous research, this paper uses the method of keyword “search-matching-summation” to describe the level of firms’ digitalization using python crawler text recognition function. This article refers to the relevant reports of the G20, the Organization for Economic Cooperation and Development, and the United Nations, and summarizes the related literature on digital technology, and concludes the keywords involved in the application of digital technology including: Digitalization, Digital Transformation, Digital Technology, Digital Platform, Big Data, Data Analysis, Data Mining, Cloud Computing, Cloud Platform, Cloud Service, Artificial Intelligence, Blockchain, Internet of Things, 5G, Machine Deep Learning, Virtual Reality, Internet Plus, Industrial Internet , 2019. TFollowing previous research, this study uses the effectiveness of patent to measure firm innovation. Patents are divided into three categories: invention patents, utility model patents and design patents. Prior researchers suggest that compared with utility model and design patents, invention patents propose brand-new technical solutions for products, methods with higher technical content and higher innovation value. Therefore, based on previous researches, this study measures firm exploratory innovation (Explore) using the total number of firm’s invention patents, and measures firm exploitative innovation (Exploit) using the total number of firm’s utility model and appearance patents.Industrial knowledge base could be divided into two types: synthetic knowledge base and analytical knowledge base. This study analyzes the knowledge base of various industries based on the existing literature, and focuses on the IT industry and the communication equipment manufacturing industry as the industry representatives of the synthetic knowledge base, and select the pharmaceutical manufacturing industry and the chemical manufacturing industry as the industry representatives of the analytical knowledge base. Industrial knowledge base was operated using a dummy variable: synthetic knowledge base was coded with a value of 0, and analytical knowledge base was coded with a value of 1.Referring to previous researches on digitalization and firm innovation, this study also controls some firm-level variables: firm age (Age), firm total assets (Asset), firm operating income (Income), and firm size (Size).This section presents the results for the hierarchical linear regression analysis. We establish the following four equation models testing the relationship between digitalization level and firm innovation. Equations 1, 2, respectively, builds the relationship between digitalization level and firm exploratory/exploitative innovation, and Equations 3, 4 are to test the moderating effect of industrial knowledge base on digitization and firm exploratory/exploitative innovation.To test the hypotheses, this study employs hierarchical linear regression and uses the entry approach and centralization variables to avoid multicollinearity. p < 0.05), which suggest that mature firms are less motivated to innovate than new start-ups. The result also shows that firm size has a significant positive effect on exploratory innovation .In p = 0.000). M2 tests the main effect of digitalization level on exploratory innovation. The addition of the main effect accounts for 12.2% of the variance in exploratory innovation over and above M1 . And the effect of digitalization level on exploratory innovation is significant and positive . This result supports H1a. M3 contains the moderator and the interactive effect to test the moderating effect of industrial knowledge base between digitalization level and exploratory innovation. As p = 0.000). The results indicate that compared with the analytical industrial knowledge base, the synthetic industrial knowledge base has a stronger moderating effect on the relationship between digitalization level and firm exploratory innovation. This result supports H2a.Among the four control variables, only firm size has a significant relationship with firm exploratory innovation . The result also shows that firm size has a significant positive effect on exploratory innovation .The same steps are taken to verify the effects on firm exploitative innovation. M4 includes only control variables. Regarding control variables, the results show the non-significant effects of firm asset  and firm operational income . The results show that firm age has a significant negative effect on exploratory innovation . M5 tests the main effect of digitalization level on exploitative innovation. The addition of the main effect accounts for 16.4% of the variance in exploratory innovation over and above M4 . And the effect of digitalization level on exploitative innovation is significant and positive . This result supports H1b. To add interpretation, we plot the interaction effect in Among the four control variables, only firm size has a significant relationship with firm exploitative innovation . Compared with exploratory innovation, the barrier of exploitative innovation is lower, so firm could easily break through such barriers and use digital technology to enable exploitative innovation. Due to the difference in the degree and direction of innovation between exploratory innovation and exploitative innovation, firms will have certain differences in the resources input and integration of knowledge of such two types of firm innovations.This study focuses on two research questions: (1) could digitization enable a firm’s ambidextrous innovation? and (2) how such relationships vary according to different industries? This study introduces the knowledge-based view to try to explain the industrial differences and focuses on the moderating role industrial knowledge base between “digitalization—ambidextrous innovation” relationship. Based on data of listed companies from China’s four industries from 2014 to 2020, this study draws the following conclusions: first, aligning with most of prior related studies, this study suggests that digitalization has a positive impact on firm ambidextrous innovation. Specifically, the effect of digitization level on exploitative innovation is stronger than that on exploratory innovation (β = 0.423, The result also shows that industrial knowledge base has a moderating effect on the relationship between digitization and firm exploratory innovation, but not on the relationship between digitization and firm exploitative innovation. Aligning with prior research, we suggest that innovation is the creation of knowledge, and firms in synthetic knowledge-based industries are mostly manifested as knowledge induction processes such as inspection, experimentation, computer simulation or time work, and less involved in knowledge deduction processes, so such firms can use digital technology in acquiring broader access to the knowledge sources required for innovation, and quickly integrating and summarizing knowledge into firm innovation. For firms operating in analytical knowledge-based industries, the innovation process starts from general scientific knowledge and derives individual and special knowledge through logical reasoning or inductive deduction. These results confirm both the industry difference and innovation type difference when exploring the effects of firms’ digitalization.This study makes two key contributions to the existing literatures and theories. First, this study contributes to the emerging digitalization research by demonstrating the positive relationship between firm digitalization and ambidextrous innovation. Although a lot of studies emphasize that ambidexterity could help firms make full use of existing advantages, and also grasp the new opportunities and possibilities for further development , many fiSecond, this study extends the boundary research on the effectiveness of digitization level through examining the contingency effect of a crucial industrial level factor—industrial knowledge base. Some existing related studies have paid attention to the role of digitalization in assisting firm innovation, and moved a step further to exploring some firm-level factors, such as firm size and entrepreneurial orientation , but fewThis study has practical implications for firms’ digital practice in different industries and also for different innovation orientations. First, this study shows that firm digitization has positive effect on firms’ ambidextrous innovation, and has different effects on different types of firm innovation. Therefore, for firms that focus on innovation, they should pay attention to the implementation of digital technology to integrate knowledge to both improve the operational efficiency and also research and development in introducing and upgrading new products. Specially, digital technology can be utilized to link product design, production, marketing and feedback, make quick responses to market demands, and speed up the pace of innovation of new products; meanwhile, digital technology could also be used to optimize business processes, improve delivery efficiency, reduce costs, and increase customer value .Second, this study suggests that firms from different industries should introduce different levels of digitization according to their requirements of innovation activities. In the process of digitalization, firms need to consider their industrial characteristics such as industrial knowledge base. Specifically, for firms conducting in industries with synthetic industrial knowledge bases such as machinery, shipbuilding, and communications, it is necessary to actively develop digitalization, build a digital layout for the whole operational processes, and improve the application scope and degree of digitalization, so as to enhance firms’ exploratory innovation capability.Based on prior literatures, this study further explores the industrial differences in the effect of digitalization on firm innovation from the perspective of industrial knowledge base. This is an exploratory study, and has some limitations, which leave some directions for future research. First, this study aims to test the industry differences of the effectiveness of digitalization, since different industries relies on various level of cognitive and reasoning of knowledge. Thus, this study introduces the moderating effects of industrial knowledge base. However, firm characteristics could also affect firm’s ways to percept and integrate knowledge, whereas industrial knowledge base couldn’t indicate firm variance. Future research could base on this study and further conjointly test both the industry- and firm- level contingency factors to extend such line of research. Second, based on prior related research, this study uses secondary data to measure the digitalization level and firm innovation. However, there may be a certain deviation from firms’ real digitalization level, and the implementation of innovation and the generation of innovation effects need to go through a certain period of time, and the effect of digitization on innovation is a gradual process. Future research could collect data through conducting longitudinal survey to capture the actual digitization level and firm innovation activities to in-depth exploration of underlying mechanism how and under what conditions digitalization would enhance firm innovation.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.QX and HL contributed to the conceptualization and results interpretation. YC contributed to the methodology, results interpretation, and reviewing and editing the manuscript. HL and KT contributed to the data collection, methodology, statistical analysis, and results interpretation. All authors contributed to the manuscript and approved the submitted version.


Spinal muscular atrophy (SMA) is a rare degenerative neuromuscular disease, mostly occurring in infants and children, leading to muscle wasting and weakness, and premature death. Due to new developments of multiple disease-modifying treatments within the last years, the interest of research in patients affected by SMA increased steadily. However, the psychosocial situation of parents as informal caregivers is still rarely addressed.This review aims to highlight quantitative and qualitative data about the psychosocial situation, caregiver burden, and needs of parents as informal caregivers for children and adolescents with SMA.A systematic literature review was performed including quantitative and qualitative original studies focusing on different psychosocial aspects and outcomes for parents of children and adolescents < 21 years of age with SMA type I–IV . We searched the following databases in November 2020 with a research update in August 2021: MEDLINE, CINAHL, PsycINFO and Web of Science.In total, 24 articles from 23 studies were selected for inclusion . The synthesis of included studies shows multiple sources of psychosocial burden for parents of children and adolescents affected by SMA: Most studies found reduced levels of quality of life, moderate to high levels of caregiver burden and distress, as well as physical and mental health symptoms. Further, findings indicate several unmet family needs regarding information, care coordination, treatment decisions, financial support, and adequate supportive care services.Parents of children and adolescents with SMA face multiple sources of psychosocial stressors, caregiver burden and various unmet family needs. To unburden families, the needs of parents as caregivers should be included in integrated care paths for SMA to improve their psychosocial situation and thus their ability to care for their children and to treat or prevent physical and mental health problems due to overburdening. Future research should focus not only on quality of life and on caregiving-related burden but should also examine the clinical relevance of reported symptoms to support the implementation of adequate support services for families affected by SMA.The online version contains supplementary material available at 10.1186/s13023-022-02407-5. Spinal muscular atrophy (SMA) is a rare autosomal recessive neurodegenerative disease, caused by homozygous disruption of the survival motor neuron 1 (SMN1) gene by deletion, conversion, or mutation and leading to muscle wasting and proximal muscle weakness . The sevSMA type I (Werdnig-Hoffmann disease) accounts for about 50–60% of all SMA cases. It is the most severe type and appears in children under the age of 6 months. Children affected by this type have hypotonia, flaccid paralysis, and are not able to sit unaided. Because of weakened muscles needed for respiration and swallowing, children with this type usually have a high risk of paradoxical breathing and respiratory infections. In addition to respiratory problems, some children with SMA type I have heart defects, both leading to an expected survival of 2 years without treatment or respiratory support –4.SMA type II (30%) occurs in children between the age of seven and 18 months. Affected children usually learn to sit, but not to stand or walk. Kyphoscoliosis usually develops, requiring surgical or orthotic interventions. Like patients with type I, respiratory insufficiency is frequent, wherefore patients often die during adolescence [Type III  occurs after 18 months of live and shows profound symptom heterogeneity. Usually, it is characterised by limited motor neuron loss, the ability to walk (with support) and a normal life expectancy, but patients experience progressive impairments like scoliosis or joint contractures , 5. PatiTo reliably diagnose SMA, patients with typical clinical features need to be tested for homozygous deletion or mutation of the SMN1 gene . In ordeUntil a few years ago, standards of care for SMA included most notably palliative care, (non-)invasive ventilation, and gastrostomy for severely affected patients as well as scoliosis surgery and orthotic management for all SMA types , 4. WithThe literature on the impact of SMA on parents as informal caregivers implicates multiple sources of burden, as well as negative psychological, social, and economic effects for affected families. To the best of our knowledge, so far, no study has systematically examined and synthesised existing literature on the psychosocial impact of SMA in children and adolescents on their parents. Therefore, the aim of our study was to review qualitative and quantitative studies on caregiver burden, the psychosocial situation, and family needs of parents as informal caregivers of children and adolescents with SMA.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020219020).This systematic literature review was conducted and reported in accordance with the items of the PRISMA checklist for systematic reviews , detailsWe searched the following electronic databases in November 2020 with a research update in August 2021: MEDLINE, CINAHL, PsycINFO and Web of Science. The primary search terms ‘spinal muscular atrophy’ and ‘SMA’ were combined with keywords addressing psychosocial- and mental health-related terms  and caregiver-related terms . Full search strings are available as supplemental material . Full texts were retrieved if title and abstract were of interest, or the eligibility was unclear. Studies, which seemed to meet the inclusion criteria at first, were mostly excluded because of missing psychosocial outcomes for parents , becausIncluded studies were classified by their methodological approach: (1) quantitative design, (2) qualitative design. Mixed methods studies were classified in one of the two categories, depending on the methodological approach of their relevant psychosocial outcome/aspect. Data of included studies were extracted by two of the authors (MB and LJ) independently and included the following information: citation details, country, study aims, study design, recruitment period and strategy, study population, and the main results of psychosocial outcomes (quantitative) or themes  for parents.To evaluate the quality of included studies, two reviewers (MB and LJ) independently assessed more than 80% (20 of 24) of the included articles using the Mixed Method Appraisal Tool (MMAT) . The MMAWe performed a narrative analysis to synthesise the data from included articles . For quaThrough database search, a total of 764 records were found with 303 being duplicates. From the review of the remaining 461 articles, 54 were selected for full text screening based on their title and abstract. After reviewing full texts, 24 articles from 23 studies were selected for inclusion  also reported on grandparents , 30, 40.Mostly, children and adolescents included in the studies were diagnosed with SMA type II (38–75% of children and adolescents), two studies only included children and adolescents with SMA type I , 34. ChiThree studies reported nusinersen and one study reported nusinersen, Zolgensma® or risdiplam as medical treatment for affected children and adolescents.Most studies compared families within SMA subtypes (type I–III) and/or different status of medical interventions  –40. OthePsychosocial and burden-related outcomes for parents were:  quality of life (n = 10), caregiver burden (n = 7), caregiver time, (indirect) costs for families, parental stress, anxiety or depression symptoms, social support, coping (n = 2) as well as family needs, and satisfaction (n = 1). All included measurements were conducted through self-assessment tools.The most reported outcome for parents was  quality of life, with 63% 10 of 16) of studies reporting on this measure. Four of ten studies , 38–40 u of studiReduced quality of life was found in parents (a) with mental (46–84%) or physical (78%) health symptoms of their own , 35, (b)Higher levels of quality of life were reported to be more likely in parents of children and adolescents with SMA type III , 38–40, Of included studies which used caregiver burden as outcome (7 of 16), four –17, 29 uIn included studies using caregiver burden as an outcome, on average, most parents reported mild to moderate burden –17, 29, Four of 16 included studies used caregiver time of parents as an outcome –17, 35. Included studies found an average caregiver time of at least five h per day in a Canadian sample  and up tThree included studies reported (indirect) costs for families that took care of a child with SMA , 17, 31.Three studies used parental stress as outcome, two of them , 37 usinTwo studies found significantly higher stress rates in parents of children and adolescents with SMA compared to parents of healthy controls , 37. WitTwo studies, using parts of the same study sample, assessed family coping with the Family Crisis Orientated Personal Evaluation Scale (F-COPES), reporting equal coping abilities for families affected by SMA and families with healthy children and adolescents , 37.Fragebogen zur sozialen Unterstützung, F-SOZU) was used in two studies, using parts of the same study sample, to measure levels of perceived social support [The German questionnaire on social support  compared to those of type III patients (46%) .Family needs were assessed in one study from Turkey  using thOne study comparing mothers of children and adolescents with adults with SMA assessed satisfaction with participation in daily life , using the Utrecht Scale of Rehabilitation-Participation (USER-P) . AlthougOf the included studies, seven articles of six qualitative studies –63 and oAs in the included quantitative studies, in all but one article which also included grandparents , informaFor children and adolescents in included studies, SMA subtypes varied across samples, with two of seven studies including SMA type I–III, whereas the rest focused on one or two of the subtypes I–III. The age of children and adolescents ranged between < 1 year and 25 years, with > 90% being younger than 18 years. The sex of children and adolescents was rarely reported (29% of studies). In three studies, children and adolescents received medical treatment (nusinersen).Qualitative findings of included articles could be divided into two main categories of psychosocial effects on caregivers: (1) family needs, caregiver burden, and psychosocial impact on parents as well as (2) experiences in the course of treatment .family needs. Parents mostly reported the need for information [The most prominent topic in the included articles (5 of 8 studies) was different kind of ormation , 62–64. ormation , 62, 64.ormation , 57, 62.ormation , 57, 62.educated health care professionals [Further, some parents felt more experienced with the disease than the child’s physician, reporting the need for better ssionals –64. Theyssionals , 64, 65.need for coordinated and integrated care, including not only medical treatment, but also psychological and practical care support. Parents often reported to feel left alone after the diagnosis, struggling to find the right solutions for their child, because of complex and time-consuming navigation through the health care and support system due to lack of clearly defined and integrated support pathways [Besides the need for information and the awareness of healthcare professionals for SMA, parents in several articles expressed their pathways , 57, 62.adequate supportive care services, like specific schooling or services for children and adolescents with physical disabilities, but without cognitive impairment [financial support, because government financial assistance only partially covered their costs for non-medical care , so that most families were additionally reliant on support from charities and fundraising [Further, families reported the need for pairment , 62. Pardraising .Caregiver burden was reported by most parents in several articles (3 of 8). One central aspect was prioritising the child’s need ahead of own care or the needs and wants of other family members. This reached from constant awareness of the child to be moved or adjusted day and night, sacrificing leisure time to the extent of moving with the family and quitting jobs for adequate schooling for the affected child [ed child , 59, 60.never-ending care tasks, causing fatigue, exhaustion, and severe lack of sleep due to limited leisure time [Financial burden due to high care costs and loss of income, as well as uncertainty about the future because of the child’s disease progression, and difficult treatment choices were also addressed in two studies [In addition, parents reported to be burdened by ure time , 59, 60. studies , 60.psychosocial impact of SMA on parents of affected children and adolescents included own  health problems like back pain due to care tasks, depression, anxiety, and high levels of distress and emotional burden, uncertainty about the future because of the child’s disease progression, a narrowing of social networks due to limited leisure time or the child’s immobility, as well as conflicts and changes in family dynamics [stresses on family finances and limited employment and career opportunities due to caregiving were reported as negative effects by some parents [The dynamics , 60, 63. parents .experience of searching for and receiving the diagnosis of their child [delay due to trusting false judgements of physicians, consulting many specialists before receiving the correct diagnosis or long distances to and waiting times for appointments and test results.Three articles concentrated specifically on the parents’ ir child , 63, 64. protracted journey accompanied by feelings of denial, stress, anxiety, and worry [state of shock, reporting numbness, denial, worry and increasing sadness [confrontation with the premature death of the child and lost expectations for a normal life [insensitive and unhelpful style of communication by the child’s physician made their situation even worse [Parents mostly experienced the way to receive the diagnosis as an nd worry , 63, 64. sadness , 63, 64,en worse .Three articles focused on parents’ expectations , 58, 62,hope to change the child’s disease progression, life expectancy and quality of life was the most central expectation for nusinersen treatment [manage the disease and live a more independent and longer life.Most parents reported that reatment , 58, 62.concerns were also reported: besides the concern of permanent cost takeover for treatments, some parents worried about treatment complications and side effects, that the treatment might be too intensive for their child and would cause pain and limited quality of life as well as long-term suffering and greater emotional pain due to the child’s increasing awareness of the disease as it is living longer [In spite of positive expectations for medical treatment options, g longer , 58.decision making, besides hope for improvement of the child’s health situation and quality of life, the relationship with the child’s treatment team was the most important factor for parents to ease a final treatment decision [In regard to decision . Parentsperception of treatment effects of nusinersen can be summarised as a reassuring effect because the clinical situation of most patients stabilised after treatment enrolment, giving them a radical change of outlook from a very limited life expectancy to new perspectives and hope for their child’s future [Parents’ s future .The aim of this study was to systematically review the existing quantitative and qualitative literature on the psychosocial situation, caregiver burden, and family needs of parents as informal caregivers of children and adolescents with SMA. Results indicate that the parents’ perspective has been studied in several geographic settings and populations with a growing interest especially within the last 10 years.By covering a broad variety in study focuses, sample sizes, outcome measurements and study quality, our review of included studies delivers a deeper and broader understanding of the psychosocial situation of parents as informal cargivers of children and adolescents affected by SMA.Parents in the included studies reported that taking care of their chronically ill child can be fulfilling and satisfying despite the high caregiving effort for families . HoweverEspecially parents of children and adolescents with more severe SMA subtypes (I–II) are strongly affected by negative consequences of the caregiving situation: besides the necessity to spend more time on caregiving and to bear higher healthcare costs , parents of children and adolescents with subtypes I–II are more likely to face difficult treatment decisions, ethical concerns, the premature death, or the palliative situation of their child –70. ThesEven though not all parents might be affected by SMA in a way that calls for additional support, the findings of the included studies indicate that receiving the SMA diagnosis can cause post-traumatic symptoms and that a substantial proportion of parents experience physical and mental health problems in the course of SMA due to the caregiving situation. These findings are in line with reviews focusing on the psychosocial situation of parents with chronically ill children and adolescents with other rare diseases  and indicate a strong recommendation for parents to receive early and ongoing assessment of their mental health needs with access to appropriate interventions to optimise parent, child, and family well-being –73.Further, the vast majority of parents as primary caregivers in the included studies were mothers (44–100%). Even though this might reflect the reality of most families in which caregivers of children and adolescents with rare and/or life-limiting illnesses continue to follow the stereotypes whereby women are the predominant caregivers  and men Due to the novelty of disease-modifying therapy options for SMA, most of the included studies were conducted before the authorisation of those therapies, leaving the question unanswered, how they could change the course of the disease and the psychosocial situation of families with children and adolescents affected by SMA. The few studies included in our review integrating parents’ experiences with new treatment options indicate that the child’s physician’s or treatment team’s expertise as well as the relationship between families and healthcare professionals might become even more important to support and help parents with difficult treatment decisions , 58. TheAlthough the review of included studies provides a deeper understanding of the caregiving situation in paediatric SMA, it also exhibits several limitations future research should try to address: Firstly, most of the included quantitative studies did not include a matched control group or SMA-specific measurements for psychosocial outcomes. Thus, as well as due to partly small sample sizes of some studies, it is difficult to assess the actual extent of caregiver burden.Secondly, there exists a broad range of healthcare costs, access to newborn screening and disease-modifying treatments across countries, SMA subtypes and time points of data collection in the included studies, which impedes general conlusions about the caregiving situation in paediatric SMA. Although studies comparing healthcare costs and quality of life in caregivers across several European countries found higher quality of life in countries spending more money per child in healthcare costs (UK and Germany) , the heaThirdly, essential descriptive data about caregivers was missing in most studies, making comparisons across studies difficult, and indicating that caregivers and their situation are not the main focus of the existing literature. The latter is also supported by the fact that only two of the 16 included studies using quantitative outcomes included measurements to assess clinically relevant psychological symptoms, hence neglecting the assessment of the potential need for psychological support for most caregivers despite findings of moderate to high general burden.Existing quantitative and qualitative literature about the psychosocial situation of parents as informal caregivers in paediatric SMA show multiple sources of burden including reduced levels of quality of life, moderate to high levels of stress and caregiver burden, as well as physical and mental health symptoms, especially for parents of children and adolescents affected by SMA type I and II. Further, studies show several unmet family needs regarding information, decision making, care integration, financial support, and supportive care services. To reduce the burden on families, healthcare policies should ensure sufficient financial support and adequate supportive care services, not only for affected children and adolescents, but also for parents, as well as care integration for affected families. Healthcare professionals should be educated to identify SMA-related symptoms, receive communication training for delivering life-threatening diagnoses and work in multiprofessional teams to address not only medical information needs, but also other psychosocial needs of families . Further research should concentrate not only on quality of life and caregiving-related burden, but also examine the clinical relevance of symptoms reported by parents in order to prevent and, if need be, treat mental disorders due to overburdening.Additional file 1. Table with PRISMA 2020 checklist.Additional file 2. Electronic database search strategy for MEDLINE, CINAHL, PsycINFO and Web of Science.Additional file 3. Table with quality assessment of articles reporting a psychosocial outcome/aspect for parents of children with SMA using the MMAT.


The National Urban Health Mission (NUHM) was launched by the Government of India as a sub-mission of the National Health Mission (NHM) in May 2013, and was the first major programmatic response at the national level to address the health issues of the urban poor .We analysed data from programme implementation, as well as government reports and data available in the public domain, from the period of 2014-2022 to highlight some of NUHM’s key achievements, while identifying a few areas that need strengthening ,6.NUHM was conceived as a truly holistic, comprehensive, and multidimensional programme with the urban poor in focus. It included several layers of core interventions, termed as “key thrust areas” by the Ministry of Health and Family Welfare (MOHFW), that could be clustered under eight topics .NUHM consisted of one Urban Community Health Centre (UCHC) for a population of 500 000 in metro cities and 250 000 for smaller cities; and one Urban Primary Health Centre (UPHC) for every 50 000 residents. Frontline workers like an auxiliary nurse midwife (ANM) for every 10 000 residents and a female volunteer or accredited social health activist (ASHA) are covering a population of up to 2500 conducted outreach services. The municipal corporations of seven megacities of India  were responsible for implementing NUHM. For the smaller towns, the state health department had oversight of implementation of NUHM. This is a unique arrangement launched in 779 cities [NUHM functionaries were trained on a wide range of topics including technical subjects, management development, communication and behaviour change, and intersectoral convergence. Despite challenges pertaining to retention of staff, a total of 8609 medical officers, 7634 staff nurses, 8031 ANMs, 1712 programme management staff, and 41 442 ULB staff were trained in various aspects until September 2022 [NUHM focused on serving the urban poor through 5025 functional UPHCs between 2014 and 2022 . CompareCommunity outreach through Urban ASHAs and community women collectives called Mahila Aarogya Samitis (MAS) have helped generate demand for preventive services and increased access to facility level care. By September 2022, 78 127 ASHAs were deployed by MOHFW and 80 852 MAS were formed to support their respective catchment populations [Under NHM, the State Quality Assurance Committee and State Quality Assurance Units have been set up in all states and union territories. The National Quality Assurance Standards (NQAS) are recognized internationally and have received accreditation from the International Society for Quality in Health Care (ISQua). As of June 2022, 150 UPHCs have been NQAS certified . The GovThe implementation of NUHM has been strengthened by establishing programme management units (PMUs) at state, district and city levels. Initiatives were taken to disaggregate urban health data in the Health Management Information System (HMIS) and coordinate with key schemes under the Reproductive and Child Health programme. This resulted in the improvement in quality of services, better coordination between urban health functionaries and community level workers, and increased outreach activities.NUHM has developed a framework for innovations and partnerships in 2018  and docuNUHM led to initiatives for increased coordination in the states for intersectoral convergence; strengthened integration with vertical programmes such as the Integrated Disease Surveillance Programme (IDSP); and increased coordination with programmes like the National Urban Livelihood Mission (NULM) and Swachh Bharat Mission (Clean India Mission). In addition, a national convergence framework was developed in 2019  and suppThe actual expenditure on NHM increased by 64% between 2016-17 and 2020-21, while that of the MOHFW more than doubled during the same period . HoweverImplementation of NUHM has provided the urban poor with an increase in access to health care as well as a choice to select public sector facilities over the costly private sector. Data from 2014 and 2017-18 (Reducing out-of-pocket expenditure (OOPE) by almost 46% for non-hospitalization cases in urban government hospitals (v), especially with urban poor having health insurance coverage below 10% (vi), is a major contribution of NUHM. It is also important to note that the average total medical expenditure, contributed largely by medicines, is about one-third of what is charged in private hospitals for the same services (INR 344 vs. INR 1038) .NUHM’s contribution to reproductive health outcomes include increase in institutional birth in urban government facilities from 42.0% to 48.3% for all and 54.0% to 62.1% for the poorest quintile between 2014 and 2017 ,17. The Apart from increasing institutional deliveries in urban areas, NUHM has contributed to increased utilization of services, reduced OOPE for health care of the urban poor, and reduced disparities in urban health care infrastructure in bigger and smaller towns. Given its initial success, NUHM needs to build on the momentum with more financing and strengthen mechanisms for partnerships, governance, and intersectoral convergence to further improve health outcomes of the urban poor.


This article reports on the results from a scoping review and a modified e-Delphi survey with experts which aimed to synthesize existing knowledge and identify research gaps on the health and health equity implications of informal employment in both low- and middle-income countries (LMICs) and high-income countries (HICs).The scoping review included peer-reviewed articles published online between January 2015 and December 2019 in English. Additionally, a modified e-Delphi survey with experts was conducted to validate our findings from the scoping review and receive feedback on additional research and policy gaps. We drew on micro- and macro-level frameworks on employment relations and health inequities developed by the Employment Conditions Knowledge Network to synthesize and analyze existing literature.A total of 540 articles were screened, and 57 met the eligibility criteria for this scoping review study, including 36 on micro-level research, 19 on macro-level research, and 13 on policy intervention research. Most of the included studies were conducted in LMICs while the research interest in informal work and health has increased globally. Findings from existing literature on the health and health equity implications of informal employment are mixed: informal employment does not necessarily lead to poorer health outcomes than formal employment. Although all informal workers share some fundamental vulnerabilities, including harmful working conditions and limited access to health and social protections, the related health implications vary according to the sub-groups of workers  and the country context . In the modified e-Delphi survey, participants showed a high level of agreement on a lack of consensus on the definition of informal employment, the usefulness of the concept of informal employment, the need for more comparative policy research, qualitative health research, and research on the intersection between gender and informal employment.Our results clearly identify the need for more research to further understand the various mechanisms through which informal employment affects health in different countries and for different groups of informal workers.The online version contains supplementary material available at 10.1186/s12939-022-01684-7. Informal employment remains a significant social and public health problem globally. Informal workers refer to all persons in employment who, “by law or in practice, are not subject to national labour legislation, income taxation, social protection or entitlement to certain employment benefits” . AlthougThe COVID-19 pandemic has led to a growing interest in the health and health equity implications of informal employment. The COVID-19 and its containment measures have had disproportionate health and socioeconomic impacts on informal workers . The preCalls for policy-relevant research on informal employment continue. These include: the International Labour Organization (ILO) Recommendation 204 on the transition from the informal to the formal economy, which was unanimously adopted in the tripartite International Labour Conference in 2015, the United Nations (UN) Sustainable Development Goal (SDG) indicator 8.3.1 under Goal 8 (Decent Work and Economic Growth) which calls for regular monitoring of the magnitude of informal employment in all countries . Other relevant SDGs include: SDG Goal 3  with Target 3.8 on achieving universal health coverage and Target 3.9 on reducing the number of deaths and illnesses from hazardous chemicals and others. These targets require labour market and welfare state policies that ensure access to health care and occupational safety and health for informal workers. Moreover, SDG Goal 5  urges all countries to “recognize and value unpaid care and domestic work through the provision of public services, infrastructure and social protection policies” (Target 5.4), reflecting the gendered nature of informal employment where women are disproportionately represented in the informal economy. These SDGs are deeply interconnected and, ideally, should be addressed in an integrated and intersectoral way.While many studies in LMICs report informal workers as having poorer working conditions and poorer health than their counterparts in formal employment, this literature has not been systematically evaluated to draw out the implications for future research and policy. Moreover, empirical evidence in HICs has only started to be published . ParticuThis study outlines the findings of a scoping review and a modified e-Delphi survey with experts which sought to map out existing knowledge and identify research gaps on the health and health equity implications of informal employment in both HIC and LMIC contexts.To guide our scoping review, we drew on micro- and macro-level frameworks on employment relations and health inequities developed by the Employment Conditions Knowledge Network (EMCONET), one of the nine Knowledge Networks established under the auspices of the World Health Organization (WHO)’s Commission on the Social Determinants of Health . The micThe macro-level framework indicates structural pathways through which health and health inequities associated with employment relations are produced and reproduced. The political power relations between the key political and economic actors are important upstream factors that determine the characteristics of labour market  and welfare state institutions and policies . In addition, the macro-level framework highlights the need for investigating the pathways through which the characteristics of the labour market and welfare state influence workers’ welfare and inequities in health according to employment relations.The micro-level framework presents several micro-level pathways – specifically harmful working conditions and material deprivation – through which employment precariousness may be linked to poor health outcomes of workers, directly or indirectly. Harmful working conditions refer to occupational exposures, hazards, and risk factors such as physical, chemical, biological, ergonomic, and psychosocial hazards. Since these harmful working conditions and material deprivation are unequally distributed across employment relations, they may have an important effect on employment-related health inequities. The micro-level framework further describes several mechanisms at a more micro-level through which employment and working conditions and material deprivation affect health inequities, including increasing the risk of developing negative health behaviours , psychosocial factors , physio-pathological changes , as well as through unequal access to health care services. Finally, cross-cutting issues like gender inequity, labour migration, and race discrimination are taken into consideration as integral dimensions of the macro- and micro-level frameworks. We used a scoping review methodology and then conducted a modified e-Delphi survey to seek expert opinions to help validate our findings from the scoping review. The literature search focuses on empirical research addressing three main questions:how does informal employment affect workers’ health?how do the health and health equity implications of informal employment vary across countries and according to gender and other social factors such as social class, race/ethnicity, age, and migrant status?what are policies or programmes to mitigate the adverse health and health equity implications of informal employment?Using a scoping review methodology , we syntScopus, Web of Science, and ProQuest databases were searched for peer-reviewed articles. Only peer-review literature was included; editorials, proposals, conference abstracts, magazine articles, and news articles were excluded. We also scanned references of a relevant article and grey literature that was retrieved from a grey literature database (Google Scholar) and targeted website searches of known organizations and institutions ). The electronic search included articles published online between January 2015 and December 2019. The search strategy was limited to English language sources.Given the scoping review objective of mapping out existing knowledge and identifying emerging gaps in research, the quality of research studies was not assessed. Accordingly, we included all the results meeting our inclusion criteria. The inclusion criteria for the articles included the following: (1) the article must be empirical research that examines the health or health equity implications of informal employment or that addresses specific policies or programmes to improve the health of informal workers; (2) the article must frame the problem as informal work. Articles addressing only precarious employment, a condition of employment that cuts across the formal and informal sectors, were excluded.Literature searches were based on title, abstract, and keywords. Two central themes of the research questions – informal workers and health – were combined to guide the search. Search terms within each theme were combined with the Boolean operator OR, and themes were combined using the Boolean operator AND. The search terms of informal workers were: “informal work*” OR “informal labour” OR “informal labor” OR “informal employment” OR “informal economy” OR “informal sector” OR “shadow economy.” The search terms of health were: “health” OR “well-being.” Two authors independently screened titles and abstracts and screened for full-text articles. Disagreement among the authors on the selection of literature was resolved through discussion until a consensus was reached among the authors.The synthesis included quantitative analysis  of the empirical research in terms of country context and the types of study methods  and qualitative analysis  of the research purpose. As described above, the macro- and micro-level frameworks provide potential subjects of research to grasp how and why employment relations affect the health of workers and their families and how to intervene to reduce inequities in health according to employment relations and conditions. In our scoping review, the frameworks were applied deductively to existing literature to determine what is known and unknown about the links between informal employment and health and the potential mechanisms linking informal employment and health inequities. In other words, the micro- and macro-level frameworks established a priori were used as a conceptual guide to categorize literature into relevant components of the frameworks and identify gaps in research that require further empirical observations and testing.To validate our findings from the scoping review and receive feedback on additional research and policy gaps on the health and health equity implications of informal employment, we conducted a modified e-Delphi survey with experts including researchers, research funders, global institutions, and other users of such research. This is a group facilitation technique that seeks to obtain consensus of expert opinions on a specific topic through the use of structured questionnaires sent electronically to participants –15. The The literature search resulted in 540 results Fig. . After sOf the 68 peer-reviewed articles, 9 were published in 2015 (13.2%), 11 in 2016 (16.2%), 14 in 2017 (20.6%), 13 in 2018 (19.1%), and 21 in 2019 (30.9%). Most studies were conducted in LMICs , including countries in Asia, Africa, and Latin America. Although only 17 were conducted in HICs including the United States, Canada, Chile, Greece, Spain, Japan, and countries in the European Union, the number increased from 4 to 2015 to 8 in 2019, indicating the growing research interest in informal employment and health in HICs as well as in LMICs. In terms of research methods, 41 (60.3%) were conducted using quantitative research methods, 23 (33.8%) using qualitative research methods, and 4 (7.4%) using mixed-methods.Table Of the 36 micro-level research studies, the majority were studies conducted in LMICs 29, 80.6%). Diverse types of informal workers were studied in LMICs, including waste workers –21, tras, 80.6%. The majority of the 36 micro-level research studies  explored occupational exposures, hazards, and risk factors as an important mechanism linking informal employment to poor health outcomes. Of the 24 studies, most explored the poor working conditions present in the workplaces, such as exposure to physical, chemical, biological, and ergonomic hazards , 44, 45.Of the 36 micro-level research studies, 7 explored barriers to accessing health care , 42–46, Of the 19 macro-level research studies, 14 explored the intersection between gender and informal employment, including 7 and 7 studies in LMIC , 48–51 aOf the remaining 5 studies of macro-level research, 2 investigated the intersection between labour migration and informal employment in Greece  and UnitOf the 13 policy intervention research studies, all were conducted in LMICs with the purpose of either evaluating a specific policy intervention or exploring the experiences of workers or key informants with existing policies or programmes. Of these, 9 were in relation to extending health insurance to informal workers –67, 3 weFindings from our scoping review are mixed on the health and health equity implications of informal employment. Informal employment does not necessarily lead to poorer health outcomes than formal employment. Our scoping review suggests that more research is needed to further understand the various mechanisms through which informal employment affects health in different countries and for different groups of informal workers.The negative impact of informal employment on the subjective well-being of individuals is empirically corroborated by studies in Colombia , Mexico Additionally, the lack of social security coverage prevented the informal workers from seeking care at a medical institution. Direct and indirect costs, such as income foregone and the time to visit a medical doctor, were cited as major barriers to accessing health care. It was common across these studies that informal workers were heavily reliant upon informal ways of dealing with health problems, rather than through formal access to hospitals, including being dependent on medicines they purchased from the drugstores alone , self-meSome studies provide empirical evidence that is counter to the negative health implications of informal employment. For example, in the 27 European Union countries, Julià, Belvis  found noOther studies attempt to account for the differences in the potential health implications of informal employment by groups of workers and welfare states. Most notably, employment informality has differential gendered effects. For example, in countries like South Africa where women experience the “double-burden” of income earning and family care, the increasing formality in employment brings greater health benefits to women than to men . HoweverFurthermore, the adverse health effects of informal employment can differ by welfare state regimes. Rodriguez-Loureiro, Vives  examine Lastly, a case study explored the experiences of individuals providing unpaid, home-based renal care in rural British Columbia, Canada . A feminFew studies discussed the politics of expanding access to health care for informal workers at a more macro level. Lavers  analyzesIn LMICs, the extension of health insurance to informal sector workers remains a key challenge. Different health insurance schemes and enrollment strategies were adopted by the governments to extend the coverage to informal sector workers and improve the retention of members, including the quasi-mandatory enrollment strategies in Tanzania  and mandBecause informal workers remain excluded from the health and safety regulatory system, diverse interventions were attempted to extend occupational health and safety to informal workers, including the development of a health and safety program by non-governmental organizations with urban street vendors in South Africa  and by cWe received 14 responses from 64 potential participants in the first round and 8 responses in the second round despite repeated follow-up. The low response rate is potentially due to the COVID-19 pandemic that affected the academic community personally and professionally. In general, participants indicated agreement with the four research gaps identified by the authors based on the scoping review: (1) a lack of consensus on the definition of informal employment within literature reviewed including health studies; (2) an underdeveloped level of understanding of different health and health equity implications of informal employment by countries, groups of workers, and sectors; (3) less attention is being given in research to explore the intersections between gender and informal employment; (4) dearth of policy studies on the relationship between informal work and health.Most of the participants agreed that there is a lack of consensus on the definition of informal employment in health studies . In particular, participants indicated that there is also considerable confusion amongst terms such as informal, precarious, and non-standard employment in research and policy contexts. Participants emphasized that these terms overlap but are not synonymous and thus need to be used based on a precise definition and not be used interchangeably. There was a high level of consensus on the usefulness of the concept of informal employment in highlighting health inequities across employment relations and working conditions , the need for more comparative policy research , more qualitative health research , and research on the intersection between gender and informal employment .The lack of consensus among respondents was only in the area of informal care and domestic work. The majority in the first round and half of the participants in the second round  agreed that unpaid care and domestic work need to be more meaningfully integrated into the concept of informal employment. Some participants commented on the need for distinguishing between paid domestic work and unpaid care work for one’s own family. While paid domestic work is already integrated into the concept of informal employment, unpaid care work remains a contentious issue. Some argued that reproductive work (unpaid care and domestic work) needs to be recognized as work or employment, because their ‘work’ enables others to work and remain productive and thus is crucial for the health of the economy and society. Others argued that unpaid care of one’s own family should not be integrated within the broad definition of informal employment. It was emphasized that policies that could improve the working conditions and level of social protections for the informal workforce are not of the same nature as policies that should be developed for unpaid caregivers for members of their own family.This scoping review synthesized available academic and grey literature on the health and health equity implications of informal employment, which is of considerable importance to further understand the pre-existing challenges faced by informal workers and the unequal impacts of the COVID-19 pandemic globally. The modified e-Delphi survey showed overall consensus about research gaps we identified in literature. The majority of participants in the modified e-Delphi survey agreed that there is a lack of consensus on the definition of informal work and a need to improve conceptual clarity.The application of well-established conceptual frameworks in the work literature strengthened our analysis of the health and health equity implications of informal employment. These micro- and macro-level frameworks held up well by providing a useful lens for characterizing and analyzing the structural pathways that can produce and reproduce associations between health or health equity and employment relations, as well as the complex pathways between employment relations and health, the mechanisms linking health and gender inequities and employment relations, and the multiple levels at which interventions can be targeted. The findings of this study showed evidence that, although all informal workers share some forms of fundamental vulnerability, including harmful working conditions and limited access to health and social protections, the related health implications vary according to the sub-groups of workers  and the country context . Given the different contexts in which labour informality is unfolding, we could also learn a great deal from context-sensitive studies – contexts including country, sociodemographic characteristics of informal workers, and labour market and welfare state institutions and policies. Moreover, the interactions between informal employment and various axes of social inequality such as, but not limited to, gender, social class, and immigration status, should be investigated in future studies .In this review, we identified relatively few articles in HICs published between 2015 and 2019 that associated informal employment with health. On the one hand, this implies that there is a perceived low frequency of informal employment in HICs that deters the investigation of the health and health inequity implications of informal employment , 9. On tHowever, despite the relative paucity of literature in HIC contexts, our findings suggest that there has been a growing interest in studying informal employment and its health implications in HICs as well as in LMICs. Most notably, most of the reviewed studies in HICs shed light on the gendered nature of informal employment with a focus on examining the health of informally employed domestic and care workers. This trend can be understood in the context of what some scholars have already suggested that ‘a new wave of informalization’ is emerging in many HICs where informal employment had seemingly disappeared in the process of modernization and remained invisible in official statistics due to its illegal nature . MoreoveAs previously noted, some participants in the modified e-Delphi survey raised a concern about the conceptualization of care and domestic work, especially in relation to incorporating unpaid care of one’s own family into the concept of informal work and resultant vagueness or conceptual fuzziness. Nevertheless, some of the included studies highlight the crucial issue of women’s unequal share of unpaid care and domestic work and its implications on women’s experiences in the labour market , 50, 55.The majority of existing research in LMICs focused on describing harmful working conditions, i.e., occupational exposures, hazards, and risk factors, such as physical, chemical, biological, ergonomic, and psychosocial hazards. While this type of research remains vital, less is known about the policies that are needed to protect informal workers and promote their health and well-being. We found few policy studies, and these were restricted to either occupational health and safety issues or the extension of health insurance to informal workers in LMICs. It is necessary to investigate the differential impacts of policy and program interventions, which are not only targeted to occupational health and safety and health insurance, but also employment, education and care policies, and the mechanisms that link interventions addressing informal employment to the health of informal workers. Given the gendered nature of informal employment, we also need more gender- and equity-focused analyses of policies that can shape the experience of informal workers.This study combining the results from a scoping review and e-Delphi survey is not without limitations. Firstly, our search was limited to empirical studies published online between January 2015 and December 2019 and written in English. By limiting the date range and language of publication, we may have missed some relevant literature. Although we found more articles were published in LMICs than in HICs, it is still possible that we did not capture the diverse and multi-faceted problems in non-English-speaking countries. Future research is needed to extend the period of publication and expand the scope of the literature review and e-Delphi survey to other languages to thoroughly integrate the research findings and enhance comparability across countries. Secondly, we included “health” and “wellbeing” into the search terms and thus were unable to rule out the possibility of inadvertently excluding relevant empirical literature that do not necessarily have the terms in the title, abstract, or keywords. However, our attempt to use well-established theoretical frameworks to map out existing knowledge can meaningfully contribute to illuminating research gaps and potential directions of future research. Thirdly, we had a low participation rate for the modified e-Delphi survey. In addition, while we acknowledge that research on informal work can be influenced by several factors including researcher and institutional interests, we did not include these types of questions in the e-Delphi survey. Despite these limitations, our findings provide a solid ground for understanding both some forms of fundamental vulnerability shared by all informal workers and different health and health equity implications of informal employment by countries, groups of workers, and sectors in pre-pandemic period. As suggested by participants in the modified e-Delphi survey, future studies should examine which combination of social, economic and health policies work best to protect the health of informal workers, for whom, under what contextual circumstances, and with what effects on health and health equity during the pandemic and beyond. This scoping review highlighted the growing production of research and policy studies focused on informal employment and their health and health equity impacts in HICs as well as in LMICs. The health and health equity implications of informal employment have been further amplified during the COVID-19 pandemic. Empirical studies conducted in many countries have shown that informal workers are exposed to harmful working conditions and poor access to health care. Without underestimating such harsh realities facing informal workers, our scoping review illuminates that the health and health equity implications of informal employment can be markedly different by groups of workers  and by countries . In this respect, further studies are required to improve our understanding of the various mechanisms through which informal employment affects health in different countries and for different groups of informal workers. In particular, global studies need to take an explicit gendered perspective, especially due to the gendered nature and health effects of informal employment. In making the transition from the informal to the formal economy, countries should consider the ways in which informal employment intersects with gender and other social factors such as social class, race/ethnicity, age, and migrant status.Additional file 1.


Publicly funded healthcare systems, including those in Canada, the United Kingdom (UK), and Australia, often use health technology assessment (HTA) to inform drug reimbursement decision-making, based on dossiers submitted by manufacturers, and HTA agencies issue publicly available reports to support funding recommendations. However, the level of information reported by HTA agencies in these reports may vary. To provide insights on this issue, we describe and assess the reporting of economic methods in recent oncology HTA recommendations from the Canadian Agency for Drugs and Technologies in Health (CADTH), National Institute for Health and Care Excellence (NICE), and Pharmaceutical Benefits Advisory Committee (PBAC). Publicly available HTA recommendations and reports for oncology drugs issued by CADTH over a 2-year period, 2019–2020, were identified and compared with the corresponding HTA documents from NICE and the PBAC. Reporting of key model characteristics and attributes, survival analysis methods, methodological criticisms, and re-assessment of the economic results were characterized using descriptive statistics. Dichotomous differences in the methodological criticisms observed between the three agencies were assessed using Cochran’s Q tests and substantiated using pairwise McNemar tests. Chi-squared tests were used to assess the dichotomous differences in the reporting of methods and explore the potential relationships between categorical variables, where appropriate. HTAs published by CADTH, NICE, and the PBAC consistently reported a broad spectrum of descriptive information on the economic models submitted by manufacturers. While common economic evaluation attributes were well-reported across the three HTA agencies, significant differences in the reporting of survival analysis methods and methodological criticisms were observed. NICE consistently reported more comprehensive information, compared to either CADTH or PBAC. Despite these differences, broadly similar recommendation rates were observed between CADTH and NICE. The PBAC was found to be more restrictive. Based on our 2-year sample of oncology, the HTAs published by CADTH matched with the corresponding HTAs from NICE and PBAC; we observed important variations in the reporting of economic evidence, especially technical aspects, such as survival analysis, across the three agencies. In addition to guidelines for HTA submissions by manufacturers, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ. Publicly funded healthcare systems in Canada, the United Kingdom (UK), and Australia use a health technology assessment (HTA) to inform drug reimbursement decision-making. In order for a new medication to be publicly reimbursed in these countries, pharmaceutical companies are required to submit a reimbursement dossier, which includes, at minimum, the clinical data used for regulatory approval, as well as a model-based economic evaluation to demonstrate the value for money of this new therapy in a given therapeutic area. Following a critical review of the manufacturers’ clinical and economic evidence by the HTA agencies, the HTA appraisals and funding recommendations associated with these products are publicly posted on the HTA agency websites.It has been shown that drug funding recommendations by HTA agencies may differ, due to differences in political priorities , agency Publicly posted funding recommendations and appraisal documents for all oncology drug indications issued by Canadian Agency for Drugs and Technologies in Health (CADTH) in 2019 and 2020 were identified. Second, the websites of the National Institute for Health and Care Excellence (NICE) in the UK and Pharmaceutical Benefits Advisory Committee (PBAC) in Australia were searched to identify publicly posted recommendations matching the same drug and indication as those identified from CADTH. Any documents published by NICE and PBAC before the end of 2021 were considered for inclusion. The final study sample comprised oncology drug submissions, for which all three HTA agencies had issued a public reimbursement recommendation.To facilitate comparison between the reporting and critical appraisal of the manufacturers’ economic models by the three HTA agencies, a set of commonly required attributes for economic evaluations submitted by drug manufacturers for reimbursement purposes was compiled from CADTH’s Guidelines for the Economic Evaluation of Health Technologies , the NICHTA agencies’ methodological criticisms of the economic dossiers submitted by manufacturers were grouped into a set of seven categories: (1) time horizon; (2) treatment benefit; (3) utility values; (4) comparator; (5) subgroups; (6) progression-free survival estimates; (7) overall survival estimates; (8) costs; and (9) extrapolation of survival data. These common thematic categories were adapted from previous studies detailing nine methodological issues described in CADTH economic guidance reports  and ten In order to explore whether reporting of methodological approaches and sources of clinical evidence considered by each agency were similar, potential relationships between variables were assessed where appropriate. Dichotomous differences in the reporting of methods and recommendation outcomes were assessed using Chi-squared tests. Where appropriate, potential relationships between categorical variables, which include several modeling characteristics and survival curve extrapolation techniques, were substantiated through Chi-squared tests. Dichotomous differences in methodological criticisms observed between the three agencies were assessed using Cochran’s Q tests. For statistically significant Cochran’s Q test results, post hoc pairwise McNemar tests were conducted to identify pairwise relationships. To support the generalizability of our results, we conducted similar analyses for HTAs, which had recommendations available from only two of the three HTA agencies.A total of 83 indications in oncology were identified from the CADTH website between 2019–2020. Matching these 83 indications with their corresponding public appraisal documents from NICE and the PBAC, 36 indications were found to have been reviewed by all three agencies, and these 36 indications  comprised our comparative study sample. Out of the 108 appraisals by NICE, CADTH, and PBAC, 14 recommendations were published by PBAC and NICE before the CADTH recommendations , with 7 in 2021.Of note, we excluded 17 indications  that were evaluated by two of the three agencies, 19 indications  that were evaluated by only one of the agencies, and 11 indications that were listed on the CADTH website, but for which none of the three agencies (including CADTH) had published a recommendation. p = 0.013). Differences were observed between the HTA agencies, in terms of reporting the instrument used to derive the utility values for CADTH (44%), NICE (92%), and PBAC (61%) (p = 0.001), reporting on equity issues (p < 0.001) and which types of analyses were conducted to deal with uncertainty (p < 0.001), with NICE reporting this information more frequently than the CADTH and PBAC. Partitioned survival models were used in approximately 70% of the models, and most models used three health states. Indirect comparisons were used in more than half of the submissions.As shown in Important numerical and statistical differences between the three HTA agencies were seen in the reporting of the methods used by manufacturers when analyzing and extrapolating survival data for cost-effectiveness modeling, with NICE reporting more often on the characteristics of the survival extrapolation methods used by manufacturers than CADTH and PBAC. For example, NICE consistently reported on whether parametric distributions were used (100% of the times), which statistical tests  were used to select the best fitting curves (94% of the times), whether the PH assumption was tested (89%), whether survival curves were fitted jointly or separately (86%), or if the extrapolations were validated (97%). In comparison, CADTH and PBAC discussed whether parametric distributions were used 56% and 78% of the time and rarely reported on the PH assumption (CADTH: 10% and PBAC: 32%). In general, the three HTA agencies tended to focus on broadly similar areas of criticism, regarding the cost-effectiveness models for a given drug/indication, most often relating to the extrapolation of treatment benefit beyond the trial duration , estimation of PFS , and estimation of OS . Notable differences between HTA agencies include NICE rarely criticizing manufacturers’ submitted time horizon (8%), while almost always criticizing extrapolations (69%), and CADTH usually criticizing both the manufacturers’ submitted time horizon (44%) and cost assumptions (64%) .p < 0.001) and PBAC and CADTH (p = 0.029). The three agencies issued the same recommendation (either positive or negative) in 39% of the included HTAs.As a partial validation of the representativeness of our results, our supplementary analyses of economic appraisals, conducted by 2 of the 3 agencies , confirmed the results of the main comparative study sample, as the observed frequencies of reporting among this alternative dataset  were broWe hypothesized that consistency would be observed for the oncology medications evaluated by the three HTA agencies, due to the same product being assessed for the same indication, based on the same or similar clinical data.We undertook a review of 36 oncology-based economic evaluations submitted by drug manufacturers for reimbursement purposes in Canada over the 2-year period, 2019–2020, which matched with corresponding submissions to the UK and Australia, for which an appraisal and funding recommendation report was publicly available from each HTA agency. Although we hypothesized that consistency of reporting would be observed due to the same product being assessed for the same indication, based on the same or similar clinical data, we found important differences in reporting. While the three HTA agencies consistently reported the baseline characteristics of these economic evaluations, NICE provided more information than CADTH or PBAC when describing the methods used for the extrapolations of survival data, despite the similar requirements for drug manufacturers to follow the same DSU guidelines . DiffereThis situation could be explained by different levels of resources assigned to the review of the economic evidence submitted by the manufacturers. For example, CADTH assigns a panel of external reviewers to critically appraise the information submitted by the manufacturer, while NICE utilizes a number of academic centers of excellence, the individual members of which may differ for each reimbursement submission. The PBAC is comprised of an independent statutory body of clinical and economic experts appointed by the Australian government. While criticisms of model assumptions varied across HTA agencies, the re-analyses conducted by CADTH and NICE to address model limitations nearly doubled the ICERs on average. It was difficult to assess ICERs re-analyzed by the PBAC, as these ICERs were presented as ranges with no point estimate, and often the range was quite wide for both manufacturer-submitted and PBAC re-analyzed ICERs. However, the percentage of positive recommendations were lower for PBAC than CADTH and NICE, which might be, at least partially, explained through different approaches to reimbursement .It is difficult to compare our study with the previous literature for several reasons. First, previous studies have examined jurisdictional differences across the published HTAs, focusing on the factors that influence HTA reimbursement recommendations from HTA agencies in Australia, Canada, England, and Scotland , differeOur current study offers insights into the reporting by three HTA agencies across a broad spectrum of economic evaluation methods, including study characteristics, common economic evaluation attributes, survival analysis, recommendation status, and methodological criticisms. The differences in recommendation status we observed across 36 oncology indications, assessed by CADTH between 2019–2020, matched with corresponding HTAs from NICE and the PBAC, might be, at least partially, explained through different approaches to reimbursement. Nonetheless, our study does corroborate recent work ,13, whicThis analysis provides useful insights into method reporting in HTA appraisal documents, but there are a number of important limitations that should be recognized. First, we conducted our study over a limited time period of 2 years (2019–2020); thus, publication bias may affect our results and conclusions. A different level of detail may have been reported in HTAs before 2019, and recent guideline updates or changes in the HTA review process at CADTH, NICE, and PBAC may impact what and how the HTA results are reported. For example, NICE announced, in 2021, an overhaul of methods to optimize evidence generation and global HTA strategy , while tIt should be noted that our sample set included 36 indications in total  that were available from all three HTA agencies out of an overall set of 83 indications . In order to ensure that our comparative sample was representative, we analyzed public recommendations made by two agencies , and the results were consistent with the main analysis (N = 36 indications). From our research, it does appear that CADTH received a slightly higher number of HTA submissions than either NICE or PBAC. One speculative explanation could be that NICE and PBAC are known to be more restrictive in their assessments of submitted dossiers, and this may or may not have prompted a number of pharmaceutical manufacturers to not submit a reimbursement dossier to NICE and/or PBAC for some indications, due to a comparatively lower probability of success. Unfortunately, we cannot demonstrate or substantiate this point using our current research and dataset.This study focuses on the recent recommendations published by three HTA agencies over a 2-year period and is, therefore, limited in both time horizon and scope. While 2 years was judged to be adequate for assessing the reporting of methods, and previous studies have used similar time scales and/or smaller sample sizes ,13,32, fBased on our 2-year sample of oncology HTAs published by CADTH, NICE, and PBAC, the variations in the reporting we observed, especially for technical aspects, such as survival analysis, suggest that, in addition to the guidelines for HTA submissions, the community of HTA agencies should also have common standards for reporting the results of their assessments, though the information and opinions reported may differ.