Telemedicine in Malignant and Nonmalignant Hematology: Systematic Review of Pediatric and Adult Studies

Introduction

Globally, we are facing a growing shortage of specialist physicians, coupled with inequity in patient access to quality care [1-3]. In America alone, only 30 specialists practice for every 100,000 people living in rural communities compared to 263 specialists in urban environments [4]. This shortage is further exacerbated when examined by subspecialty, making it progressively more difficult for patients to reach their physicians and obtain necessary treatments [4]. Thus, health care officials have turned to the field of telemedicine to leverage technological tools with the goal of expanding and optimizing the delivery of medical care [3].

Telemedicine is defined as the use of teleconferencing interventions to provide and deliver health care to patients [5]. Although telemedicine is classified under the broader term, “telehealth,” ambiguity surrounding which forms of technology each category encompasses still exists, and both terms are often used interchangeably [6]. Telemedicine is a subset of telehealth, which is defined as the use of technology in any aspect of health care. Telemedicine is specifically utilized for clinical patient care, not exclusively for research purposes.

Telemedicine has grown in parallel with society’s growing desire for convenience, efficiency, and productivity, and today, frequently used modes of telemedicine include videoconferencing, email, wearable devices, cellular phones, and various mobile apps [3,6]. These new systems of telemedicine are promising for mitigating the current challenges in health care reform, since they offer medical professionals the novel opportunity to extend their presence to settings outside of their immediate reach [3]. In doing so, telemedicine presents health care industries with the potential to provide more cost-effective treatments, support patient self-management, respond to the growing demand for specialists, and uncover avenues for advancing the practice of medicine in underserved areas worldwide [3,6-9]. Furthermore, access to personal and mobile technologies is ubiquitous [10-14], which has provided an opportunity to optimize digital health care delivery approaches, including telemedicine. However, despite these benefits, there remain obstacles to implementing telemedicine in daily practice [15,16]. Barriers, including stable internet access, cost, and patient desire for in-person appointments, must be addressed for telemedicine to reach its full potential [15,16]. Nevertheless, there has been growing evidence to support the utility and clinical applications of various digital approaches for health care delivery, including telemedicine, across pediatric and adult populations with or without chronic medical conditions [17-39], although the cost-effectiveness remains unclear [40,41].

In the field of hematology, recent advances in telemedicine have been used to conduct patient visits, monitor treatment side-effects, and perform consultations [42-45]. During the current COVID-19 pandemic, telemedicine use in outpatient settings, such as hematology clinics, has increased significantly owing to stay-at-home orders and efforts to lessen exposure to ill patients [46,47]. Videoconferencing interventions have proved to be a safe and efficient way for health care providers and patients to continue managing and monitoring chronic health conditions, especially for sickle cell disease and other hematological conditions [48]. Additionally, both adult and pediatric populations in underserved areas have benefitted from telemedicine’s ability to connect them to specialists in different cities [48].

In this systematic review, we evaluated the evidence available in the literature to analyze the feasibility, acceptability, and potential benefits of telemedicine interventions in malignant and nonmalignant hematology and assess the current limitations of utilizing these interventions. Owing to the heterogeneity of the included studies, the methods by which feasibility, accessibility, and clinical outcomes were assessed vary among the studies. In this review, we use these terms broadly to encompass the different interpretations of these objectives. We more specifically define each study’s main objectives in the Results section.

Methods

Guideline

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting of evidence across the studies we reviewed [49].

Article Retrieval

A librarian, in collaboration with other review authors, collaboratively developed the highly sensitive Medical Subject Headings (MeSH) term–based search strategies and ran searches in the following databases: PubMed MEDLINE, Controlled Register of Clinical Trials (Cochrane CENTRAL from Wiley), Embase, and CINAHL (EBSCO), on February 7, 2018 (Multimedia Appendix 1). The bibliographies of hand-searched articles that had been previously identified were also included. The search strategy focused on articles that studied telemedicine and telehealth interventions for malignant and nonmalignant hematological conditions in both pediatric and adult populations. No date limits were applied to the search. On October 1, 2020, another literature search was conducted on PubMed to identify articles that were published since the last literature search and that met the inclusion criteria. The second literature search utilized the same search strategy as the first search.

Study Selection

The inclusion criteria were as follows: (1) studies involving pediatric or adult populations with malignant or nonmalignant hematological conditions, (2) studies involving telemedicine or telehealth interventions, (3) studies that included feasibility, acceptability, and clinical outcomes of the interventions as the primary or secondary outcomes, (4) original research articles, and (5) studies designed as a randomized controlled trial (RCT), cohort study, pilot study, retrospective study, or cross-sectional study. “Telemedicine” and “telehealth” are often used interchangeably, so both terms were relevant to the search despite having different semantic meanings. The exclusion criteria were as follows: (1) studies not related to hematology, (2) studies without a telemedicine intervention, (3) nonclinical research studies, (4) abstracts only or nonoriginal research papers, and (5) studies not in English.

Data Extraction

A standardized format was used for data extraction. Data items in the extraction form included first author name, publication year, country, malignant or nonmalignant hematological condition or disease focus of the study, participant age, participant age subgroup (adult or pediatric), study design and setting, telemedicine intervention type and description (telephone, remote management, videoconferencing, etc), study purpose, and main outcomes. Two authors coded all included articles individually. Disagreements were resolved by discussion.

Quality Assessment and Evidence Strength

Studies described in each article were evaluated for the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach [50]. This method evaluates four key domains, including consistency, directness, risk for bias, and precision of the evidence. Two authors graded all included articles individually. Disagreements were similarly resolved by discussion, if needed.

Results

Literature Search

Our literature search identified 1047 records. After removing duplicates, 878 articles remained. Two authors independently screened the titles and abstracts of 878 records, and 774 were excluded. Two authors independently screened the remaining 104 full-text articles, and 32 met our inclusion criteria for eligibility. The study flowchart and reasons for exclusion of full-text papers were documented in an adapted PRISMA study flowchart (Figure 1). We did not identify any non-English articles that met our inclusion criteria.

‎View this figure

A total of 32 articles were included in this systematic review. Most (25/32, 78%) studies were conducted with adults [42,51-74], while the remaining (7/32, 22%) were conducted in the pediatric population [75-81]. The studies addressed whether a telemedical intervention for patients with malignant and/or nonmalignant hematological conditions is a safe, feasible, and efficacious method of health care provision.

Description of the Included Studies

Table 1 and Table 2 summarize study characteristics for the pediatric and adult populations, respectively. Out of the 32 studies, 16 (50%) were conducted in the United States [52,53,55-57,60,62,63,65,69,71-73,77,78,81], 6 (19%) in Canada [58,64,68,74,75,79], 2 (6%) each in Australia [42,61], India [51,76], and Italy [54,70], and 1 (3%) each in Brazil [80], France [59], Germany [66], Ireland [67], and Rwanda [81]. Although the search retrieval included results published since 1980, the earliest eligible study was from 1998, which corresponds to our knowledge of when telemedicine was first introduced [71]. The most recent study was published in 2018 [56].

The sample size ranged from 1 [74] to 217,014 [62], with a median of 157 and a mean of 7977 participants per study. Overall, 21 studies enrolled ≥100 participants [51,53-60,62,63,65-70,72,73,76,80] and 11 had <100 participants [42,52,61,64,71,74,75,77-79,81].

Of the 32 included studies, 12 (34%) studied malignant hematological conditions [42,53,58-61,64,67,69,77,80,81], 18 (59%) studied nonmalignant conditions with percentages [51,52,54-57,62,63,65,66,68,70-74,76,78], and 2 (6%) studied both malignant and nonmalignant conditions [75,79].

Methodological Quality of the Studies

Of the 32 studies, 11 (34%) were pilot studies [42,51,62-65,71,75,76,78,80], 9 (28%) were retrospective studies [55-58,60,67,70,72,81], 6 (19%) were RCTs [52,53,61,69,73,77], 2 (6%) were cross-sectional studies [68,79], 1 (3%) was a case study [74], 1 (3%) was a pre-post study [54], 1 (3%) was a noncomparative prospective study [59], and 1 (3%) was a prospective cohort study [66]. Of the 6 RCTs, 1 (17%) was a single-blinded study and the remaining 5 (83%) had no blinding. Follow-up activity after the telemedicine interventions was tracked in six of the studies in the forms of postintervention neuroimaging examination (n=1, 17%) [77], follow-up assessments (n=3, 50%) [52,53,64], number of patient visits (n=1, 17%) [62], and interview (n=1, 17%) [82]. Based on the GRADE criteria, four included studies were rated as “moderate” [52,53,69,77], four were rated as “low” [54,61,70,79], and 24 were rated as “very low” [42,51,55-60,62-68,71-76,78,80,81]. The “low” and “very low” ratings were mainly a result of the type of study and indirectness of evidence.

Description of Telemedicine Approaches

Table 3 and Table 4 provide detailed descriptions of the study purpose, telemedicine intervention used, and main findings of the included pediatric and adult studies, respectively. Additional study outcomes for pediatric and adult studies are also reported in Multimedia Appendix 2 and Multimedia Appendix 3, respectively. There were the following three main categories of telemedicine interventions in the included studies: video (n=9) [53,58,64,71-75,78], telephone (n=9) [52,55,59-61,65,67,76,81], and web (n=14) [42,51,54,56,57,62,63,66,68-70,77,79,80]. Video interventions used cameras and videoconferences to visually connect the patients to the providers. Telephone interventions involved nurse triages, counseling sessions over the phone, and telephone help lines available to patients 24/7. Web-based telemedicine interventions included online interfaces for patients to send and store data and to monitor their conditions from home while still maintaining intermittent contact with practitioners.

Study Outcomes in Video Telemedicine Interventions

Pediatric Video Interventions

Adler et al reported greater than 80% case review round attendee satisfaction with telemedicine case consultations and patient care education for children with cancer and blood disorders [75]. Improved satisfaction and communication among health care providers and caregivers with the use of videoconferencing at home for children with hemophilia were also noted by Jacobson et al [78].

Adult Video Interventions

Many telehealth nursing sessions have shown positive outcomes for patients with malignant hematological conditions [53]. Likewise, patients with hematological malignancies felt that they could talk easily and openly with the nurse who led telemedicine follow-up visits in between visits with the oncologist [64]. Telemedicine reportedly improved productivity [72] and increased mean cognitive skills quotient scores for patients [73], but caused no significant decrease in clinic encounter times [71]. Wright et al reported high follow-up adherence rates, good condition management, and high satisfaction for e-clinic visits in allogenic blood and stem cell transplant patients [74]. Clarke et al found that teleconsults in British Columbia were most often used with medical oncologists [58].

Study Outcomes in Telephone Telemedicine Interventions

Pediatric Telephone Interventions

Agarwal et al found comparable health outcomes at a lower cost through the implementation of an online information technology database platform for patients receiving bone marrow transplants [76]. Stulac et al found that 13 of 24 Rwandan patients with pediatric cancer were in remission at the end of data collection following collaboration with United States–based physicians and nurses through telemedicine interventions [81].

Adult Telephone Interventions

Telephone therapy was utilized by Applebaum et al, which resulted in decreased depressive symptoms in hematopoietic stem cell transplant survivors with concurrent posttraumatic stress disorder [52]. For patients taking anticoagulants, Blissit et al noticed that telephone interventions led to significantly lower rates of bleeding in patients compared to face-to-face visits [55]. However, Philip et al did not see a significant difference in time within the therapeutic range, hospitalization, or bleeding with a telephone-based anticoagulation service [65]. Reid et al and Flannery et al utilized phone services to address patient questions and symptoms [60,67]. Reid et al noted that 36.8% of calls led to a medical assessment [67]; however, Flannery et al reported no notable improvements with the telephone triage [60]. Biweekly calls for monitoring vitals, side-effects [59], and telephone counseling [61] have all shown benefits for patients with malignant hematological conditions.

Study Outcomes in Web-Based Telemedicine Interventions

Pediatric Web-Based Interventions

Cox et al found that patients, families, and caregivers had high rates of intervention participation and reported a positive experience with the introduction of a remote automated working memory intervention for childhood cancer survivors [77]. Telemedicine interventions also received high ratings from primary care providers and resulted in hematology consult deferral, according to Johnston et al [79]. Similarly, Pedrosa et al reported positive outcomes, with decreased rates of mortality, early death, and acute lymphoblastic leukemia relapse following implementation of a telemedicine program that allowed for knowledge sharing between high- and low-income countries [80].

Adult Web-Based Interventions

Based on a survey by Checchini et al, more than half of patients with nonmalignant hematological disorders preferred e-consults over face-to-face visits, and satisfaction was noted in all providers [57]. Breen et al found increased feelings of empowerment, health awareness, and medication adherence with the use of a telemedicine-based smartphone app that directly transmitted health data to the hospital for patients with blood cancers [42]. Najafi et al also noted that the majority of hospitalists and consultants found e-consult to be a feasible administration of subspecialty health services at a remotely-located hospital [63]. Primary care providers were satisfied with e-consult technology in a survey by Skeith et al, especially since 47.5% of in-person visits were avoided through the use of this telemedicine intervention [68]. Kirsh et al also reported a decreased number of face-to-face visits in patients using e-consult telemedicine interventions [62]. Additionally. Burwick et al saw that e-consults for hematology cases in patients with monoclonal gammopathy of undetermined significance led to a decrease in the time it took to complete the consultation [56]. In a study by Syrjala et al that included cancer patients treated with hematopoietic stem cell transplantation, over half of participating patients used an online platform and reported the need for staff contact one or more times per day, usually for minor assistance [69]. Barcellona et al reported an increased number of blood checks, fewer missed international normalized ratio checks in the home monitoring group, and a significant increase in the time within the therapeutic range for patients treated with vitamin K antagonists when using a smartphone app to monitor treatment [54]. Vitamin K antagonist users also had lower rates of bleeding, hospitalization, and all-cause mortality with the use of an online electronic file [66]. Electronic medical record implementation for remote anticoagulation management, however, showed no significant difference in the time within the therapeutic range or major complication rates in nursing homes [70]. Agrawal et al found that a call center allowed for increased recruitment of blood donors [51].

Discussion

Principal Findings

Overall, the vast majority of telemedicine interventions studied in this systematic review were shown to have a positive or neutral impact on patients, families, and health care providers. Telemedicine was found to be particularly useful for rural communities, patients in countries with less access to care, and patients with chronic conditions that require routine monitoring and communication with doctors [53,64,71-73,75,78,80,81]. Most studies showed improved or similar outcomes in groups that utilized telemedicine compared to those that did not. However, more research would be beneficial to determine telemedicine’s role in hematology and future implications for its use in the clinical setting. This evidence could also potentially increase patient satisfaction and patient-reported health outcomes.

Telemedicine Interventions in Hematology: Expansion of Team-Based Medicine

In the realm of hematology, many new telemedicine interventions have emerged in recent years to expand the reach of specialty health care and improve patient outcomes [83,84]. Kulkarni et al reported that school-based telemedicine has provided access to multidisciplinary teams for the treatment of hemophilia and related bleeding disorders [84]. In patients who have undergone hematopoietic stem cell transplantation, therapy compliance and surveillance are seen to be good areas to implement telemedicine [83].

Telemedicine Interventions in Hematology: Areas of Further Study

Future use of telemedicine in hematology and other subspecialties should focus on increasing the usage of videoconferencing with physicians from patient homes and making telemedicine more accessible to a wider range of patient populations [85]. This is especially the case for rural areas or regions where specialty health care and access to medical resources are limited [86]. The current COVID-19 pandemic has shown the value of maintaining and developing different ways of patient care, such as through the increased implementation of telemedicine in clinics and hospitals [87]. Various specialties should investigate ways in which they can best implement telemedicine interventions into their own field to improve access and care [86]. The next steps should include the wide use of triage systems that allow patients to be screened for telemedicine use eligibility [87].

Telemedicine Interventions in Other Medical Specialties

In addition to the use of telemedicine in hematological conditions, it is widely used in various other medical specialties [88-93]. Meta-analyses on telemental health care have reported that applying telemedicine to psychotherapy not only improves patient satisfaction and access to care by circumventing the stigma of seeking in-person mental health care, but also offers a more financially prudent and flexible method of treatment [88]. Telemedicine has also been reported to contribute to shorter lengths of hospital stay and lower hospital mortality [90]. Multiple studies have shown it to be a cost-effective and accessible provision of mental health services [88]. Positive user outcomes with telehealth implementation in emergency rooms have indicated another area of potential use [91]. Similarly, telemedicine has been seen to help in the secondary prevention of stroke and in transient ischemia attack patients, but more research is needed to bolster evidence [93]. Cancer survivors generally had positive attitudes toward self-management and eHealth, but there was variation in the care needs depending on the type of cancer [92]. Telemonitoring is rarely used in prenatal care, but has potential in monitoring pregnant women who are at risk for preterm delivery [89]. These studies emphasize the positive experiences patients and providers have had with telemedicine in various fields of medicine, which further suggests that telemedicine is feasible, accessible, and beneficial. Many of the telemedicine interventions used in these other medical specialties can also be applied to the setting of hematology.

Barriers to Telemedicine

Though studies indicate high reports of satisfaction from patients and providers in malignant and nonmalignant hematology [57,68,79,94], the incorporation of telemedicine in modern medicine still faces limitations and organizational barriers, including legal liability, cost and reimbursement, and confidentiality concerns [15]. Patient barriers, such as age, computer literacy, and education, also make telemedicine difficult to implement universally [15]. Additionally, technological barriers, including inadequate bandwidth, technically challenged staff, and licensing issues, can limit the scope of telemedicine [15]. There are also concerns regarding the availability of resources in languages other than English [82], lack of notable improvements with telephone triaging [60], efficiency of face-to-face visits [71], and quality of care delivered via e-consult [63]. Funding for both staff and equipment, privacy concerns, internet connection, and home recording all need to be addressed when considering the feasibility of telemedicine [15,95-97]. Since the cost-effectiveness of telemedicine varies across delivery settings [9], more research needs to be done to substantiate evidence of improvement in patient outcomes with the use of telemedicine. Furthermore, the ethics of telemedicine and digital health use in the clinical setting must be discussed. The ethical and legal concerns regarding the use of telemedicine have delayed the rapid widespread implementation of these technologies in multiple aspects of health care [98-100]. Specifically, data confidentiality, patient privacy, physician-patient relationships, and informed consent are all areas that need to be addressed [99,101-103]. Further work must be done to ensure that data management is conducted properly and the social implications or risks are communicated clearly to patients and physicians using telemedicine in practice [99,101-103]. However, despite its barriers, the ability of telemedicine to mediate many of the shortcomings associated with traditional face-to-face consultations still makes telemedicine particularly attractive to many fields, especially hematology.

Strengths

Our systematic review has a number of strengths. First, we conducted our review following the recommendations for rigorous systematic reviews [49]. Second, we used a highly sensitive and specific search strategy guided by a librarian information specialist. There was no restriction on the country of study in order to minimize publication bias by identifying as many relevant studies as possible. Additional resources were searched, including published systematic reviews, clinical trial registries, and multiple electronic databases. Third, we employed no date restrictions on our search; no included articles were published prior to 1998. Therefore, the possibility that we missed earlier studies is very small. Finally, two authors completed the review process independently at all stages.

Limitations

Some potential methodological limitations of our systematic review must be addressed. First, some relevant articles could have been missed in our literature search, despite our comprehensive search strategy in different databases. Second, articles included in the review were strictly peer-reviewed, which could cause publication bias from reporting only positive study results [104]. Third, the ranges of sample size and age, differences between malignant and nonmalignant conditions, and types of telemedicine interventions varied greatly among the studies. Lastly, the number of studies eligible for the review was relatively low; however, this may be a result of the specificity of hematological conditions and the limited number of available publications about the topic.

Conclusions

Telemedicine is a recognized and cost-effective way of managing hematological conditions. Evidence from this systematic review suggests that telemedicine provides similar or improved health care compared to traditional face-to-face care. Videoconferencing, telephone-based services, and web-based services were also well received by patients, families, and health care providers in both pediatric and adult settings. However, due to the limited total number of articles and low quality of evidence of the included studies, further research must be done to determine the efficacy and plausibility of widespread implementation of telemedicine in hematology.