1 BACKGROUND

Retinoblastoma (RB) is a childhood eye cancer which affects children worldwide, but has higher mortality rates in the African context (Dimaras et al., 2015; Selvarajah et al., 2021). RB is curable, with a ~96% survival rate observed in high-income countries like Canada (Selvarajah et al., 2021); in low-and-middle-income countries (LMICs), mortality remains high, but targeted research and capacity building efforts, such as those observed in Kenya are starting to change this (Dimaras et al., 2015). For example, the establishment of the Kenyan National RB Strategy (Hill et al., 2016), aimed at early RB detection and enhancing quality of care to improve patient outcomes, led to an increase in RB survival from 30% (Nyamori et al., 2012) to 70% (Namweyi Nandasaba, 2015). Given its curability, the World Health Organization has designated RB an index cancer in its Global Initiative for Childhood Cancer, aiming to improve survival to 60% by 2030.

As a heritable cancer syndrome, high-quality genetic testing is essential for comprehensive diagnosis of RB. Predisposing RB1 pathogenic variants can be identified with 95% sensitivity for RB patients (Rushlow et al., 2009) and testing for these variants has been found to be cost-effective in North American settings (Noorani et al., 1996). Early prediction of disease, facilitated by genetic testing in at-risk infants, prompts early and frequent screening to treat tumors as soon as they appear (Dimaras et al., 2015). This leads to better visual outcomes with less intensive therapy (Soliman et al., 2016). Coupled with effective genetic counseling, genetic testing can also predict future cancer risk, and support at-risk individuals to undergo tailored follow up, access timely care, make informed lifestyle and family planning choices, and cope with diagnosis. However, genetic testing and formal genetic counseling for RB is mostly unavailable in the African healthcare setting. Researchers and policymakers agree that genetic services are becoming increasingly more relevant for improved health outcomes in LMICs (Tekola-Ayele & Rotimi, 2015).

There is a need to improve patient-facing health materials, particularly for genetics, yet studies show that the patient voice is rarely included (Wynn et al., 2018). We conducted a series of focus groups with survivors and parents of children with RB (Gedleh et al., 2018), propelled by evidence showing that studying patient perspectives can inform the design of genetic services (Adedokun et al., 2015; Gillham et al., 2015). Our previous study revealed that Kenyan parents and survivors of RB lacked complete understanding of their genetic diagnosis, and demanded more comprehensive delivery of genetic counseling, including tangible resources to aid their understanding (Gedleh et al., 2018). The work described in this study is a direct response to this request from the patient community. The goal of this study was to co-develop, with patient families, a genetics educational booklet for retinoblastoma and demonstrate proof-of-concept for its future evaluation in a real-world study.

2 METHODS

3 RESULTS

3.1 Phase I: Development of educational booklet

3.1.1 Knowledge users

Fifteen healthcare knowledge users and five patient knowledge users participated in three to five consultations each. Table 1 shows demographic details of the knowledge user groups.

TABLE 1. Phase I knowledge user group demographic details.

Knowledge users (n = 20)	n	%
Healthcare	15	75
Role
Physician	8	53
Nurse	4	27
Counselor	2	13
Advocate	1	7
Affiliation
Hospital	11	73
Advocacy Group	3	20
Ministry of Health	1	7
Patient	5	25
Role
Parent/Guardian	5	100
Survivor	0	0

3.1.2 Booklet content and design

An iterative, phased design process produced an educational booklet rich in images and stories, with complex genetic information described in lay language. The images show cartoon families visiting doctors, and simplified diagrams of cells and genes (Figure 1). The booklet employs characters and stories to explain the nuances of heritable and non-heritable RB. Core concepts covered in the booklet include: definitions of DNA, genes, cells, and pathogenic variants; cancer development; the genetic development of RB and inheritance patterns; consequences of heritable RB versus non-heritable RB; and treatment. The booklet also tackles common myths about the origins of cancer (i.e., witchcraft or curse) to curb the stigma associated with heritable cancer.

3.1.3 User guide

An unexpected result of our knowledge user-directed process was that the knowledge users suggested the educational booklet be used in two ways: (1) as a take home for patient families (as initially anticipated); and (2) in educational sessions led by trained facilitators (e.g., nurses, counselors, and patient navigators), according to directions found in a user guide (Figure 1). A user guide was therefore designed to include suggested language for explaining concepts in the booklet, discussion points, and additional (non-essential) information to cover, depending on level of patient understanding. The user guide also instructed clinicians on how to employ a ‘teach-back’ method to check for patient understanding. The intention is to promote dialogue between health professionals and patients that eliminates confusion, a feature supported by the literature (Noorani et al., 1996; Rushlow et al., 2009). Knowledge users also suggested that the content of booklet could be printed as a large format flipchart, to better serve as a visual aid during the educational sessions.

4 DISCUSSION

Genetic testing and counseling are essential for cancer care (American Society of Clinical Oncology, 2003), but availability, access, and quality varies worldwide (Hawkins & Hayden, 2011; He et al., 2014; Hill et al., 2015). This is in part attributable to a false impression by funders and policymakers that genetic services are irrelevant for LMICs (Wonkam et al., 2010). Where genetic services do exist, it is predicted that they will soon be unable to meet their increasing demand (Trepanier & Allain, 2014). With increasing demand for cancer genetic services in LMICs like Kenya, new models of service delivery are needed (Trepanier & Allain, 2014). Specifically, these models should take in to account the unique ethical, social, and cultural context of the setting they are being designed for (Zhong et al., 2021). Our prior work defined a model for delivery of clinical genetic services in Kenya that emphasized the need to develop novel educational tools, and a patient- and community-centered approach to genetic counseling (He et al., 2014). Our current study represents a novel patient-oriented approach to begin identifying and addressing such issues while filling the gap in genetic counseling services in Kenya. Furthermore, by focusing the work on the prototypic heritable cancer RB, our results have wide relevance and applicability to the many countries, inclusive of LMICs and also HICs, currently shaping childhood cancer policy to improve RB outcomes and quality of life.

Comprehensive understanding of RB and its heritable consequences is important so that appropriate interventions, such as regular eye examinations for at-risk infants, are sought out early enough to save lives and vision. The educational booklet described in this manuscript showed promise in meeting this aim, as it was developed in direct consultation with the patient community. As a result, the educational booklet contains the content that families want and need to know, described in an understandable format. The combination of factual content and stories used in the resultant booklet has been proven effective in relaying health information (Kitamura et al., 2011) and communicating difficult concepts to patients and families with low literacy (Houts et al., 2006). Furthermore, the images and language choices, particularly in the Swahili version of the booklet, were tailored to the cultural context of Kenya. Yet, even with these culturally specific nuances, the broader content in the booklet has potential applicability to other geographic or cultural regions struggling with communicating information about heritable cancer.

Genetic diagnoses place a significant psychosocial burden on families (Eijzenga et al., 2014; Wonkam et al., 2014). Culture and society can influence how people interpret genetic health information (Solomon et al., 2012). Thus, engaging patients in designing genetic counseling interventions is important so that innovations are useful and relevant. However patient engagement is challenging in the LMIC context (Janic et al., 2020); while we were able to recruit 11 patient partners, we did not achieve a 1:1 ratio of patients to non-patients recommended for such work. Importantly however, the patients who did participate were able to provide important insights into the local context, particularly the need for financial support and psychosocial counseling to support the uptake of genetic information. Also of note, one participant indicated that they would share the booklet with friends and family to reduce stigma around cancer, which is prevalent in the Kenyan context. The issue of stigma is increasingly being reported in North American context as more diverse populations are being included in research about disclosure of genetic results to family (Hunter et al., 2023).

Another outcome of our knowledge user-guided process was the development of a user guide to assist health professionals in leading counseling sessions. This was suggested by health care knowledge users, noting that they required more support in information delivery; the user guide was suggested with the intention to help standardize the delivery of genetic information, particularly in a context where genetic counselors are rare. In our evaluation, the user guide and educational session were not evaluated, but instead the booklet was independently reviewed by participants. An educational session intervention would need to be developed and tested in future. Previously, to address the challenge of scarce genetic counselors in Kenya, we implemented and tested a role-play based workshop to improve health professional understanding and skills regarding genetic counseling for RB (Hill et al., 2015). This workshop could be modified to train facilitators on the use of the booklet and user guide. Encouragingly, there are more and more formal programs starting to introduce genetic counseling in sub-Saharan Africa through twinning, for example, in Ethiopia (Quinonez et al., 2021).

The preliminary intervention has shown promise in improving knowledge and confidence in RB genetics among parents of children with RB. Interestingly, the booklet inspired new questions on screening for second cancers and prevention of RB, which are key research questions yet to be solved globally. Importantly, it also revealed that it could be improved to better articulate the limited evidence on the role of environmental factors, such as diet, on RB development, to alleviate worry or guilt in parents.

Genetic testing can identify the precise pathogenic variant carried by a proband, the discovery of which is essential to predict the cancer in at-risk family members or confirm non-heritable RB status. The Kenyan Ministry of Health guidelines for RB care (Ministry of Health Kenya, 2014) include recommendations for genetic testing and counseling; however, since few Kenyan families have been able to access RB genetic testing (via North American or European laboratories, paying out of pocket), most patients are counseled by their clinician based on their phenotype or known family history of disease. Therefore, the educational booklet was designed and tested in the current context of the absence of genetic testing for RB. However, the original study that indicated a need for more education also indicated that patients want improved availability and access to genetic testing—motivated by the idea of preventing or minimizing the effects of the cancer on future generations (Gedleh et al., 2018). Even the patients in the current research had questions about prenatal detection and early intervention, though it is currently only available in the European (Gerrish et al., 2019) and North American (Soliman et al., 2016) contexts. Yet, questions like the ones from the patients in this study, as well as research on other heritable cancers in other parts of Africa, indicate that cancer genetic services are desired by the patient community; a study from Nigeria even showed that cancer patients are willing to pay out of pocket for cancer genetic testing (Adejumo et al., 2023).

We note that the main limitation of our evaluation was the small sample in Phase II, a result of limited time and funding. Given these anticipated logistical constraints, the study team set out to conduct a small preliminary study to gauge the feasibility of proceeding with a larger-scale evaluation. Moreover, the small sample size provided an unexpected opportunity for the study team to assess how patient engagement could be enhanced, actively involving parents or survivors as partners in the future evaluation; these insights have been presented in our published model for patient engagement in LMICs (Janic et al., 2020). Embedding patient partners into our study team is expected to facilitate recruitment and retention of a sufficient sample size in future study (Chhatre et al., 2018).

In summary, our preliminary evaluation indicated feasibility of future implementation and formal evaluation of the booklet for its efficacy in increasing knowledge and health decision making regarding RB genetics. Patients were critical to its development and offering unique insight from the lived experience of being affected by heritable cancer in the Kenyan context. Given that genetic testing for RB is being developed now for Kenya, the current intervention could be expanded to include a patient-facing genetic testing report to aid counseling sessions for those who have undergone testing.

AUTHOR CONTRIBUTIONS

All authors meet the 4 ICJME criteria as follows: Conception or design of the work (HD) or acquisition, analysis, or interpretation of data for the work (all authors); drafting the work (TI, MB, AH, and HD) or reviewing the work critically for important intellectual content (KK, JK, FN, LN); final approval of the version to be published (all authors); and agreement to be accountable for all aspects of the work (all authors). Author HD confirms that she had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All of the authors gave final approval of this version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts to disclose.

ETHICS STATEMENT

Human studies and informed consent: This study adhered to the principles set out in the Declaration of Helsinki. Phase I was exempt from Research Ethics Board approval as it was not a research activity, but development of an intervention with knowledge users. Ethical approval for Phase II was obtained from the University of Nairobi (Protocol #UP704/10/2018). Written informed consent was obtained from all participants in Phase II.