Development of a Patient-Centered Pathway of Care for Retinoblastoma Patients: A Mixed-Methods Pilot Study.

Introduction Retinoblastoma treatment and follow-up is complex and varies between patients. Pathways of care can enhance quality of care, patient outcomes, safety, satisfaction, and resource optimization. Developing a pathway of care for retinoblastoma was identified as a top research priority by the retinoblastoma community. This study aimed to co-design and pilot a pathway of care called the "Retinoblastoma Journey Map" tailored for caregivers of newly diagnosed children with retinoblastoma. Methods A working group of patients, health professionals and researchers used human-centred design to ideate, prototype and refine the Retinoblastoma Journey Map. Caregivers of affected children were recruited to use and evaluate the Map. Mixed-methods data was collected on feasibility, acceptability, usability and perceived impact on communication, self-efficacy, anxiety, depression, and the quality of physician-patient interaction. Results The Retinoblastoma Journey Map consisted of an illustrated roadmap with 25 child-friendly stickers covering clinical treatment, medical education and milestones. Quantitative analysis revealed that the Map was feasible, acceptable, and usable; however, no significant effect on communication, self-efficacy, anxiety, depression or quality of physician-patient interaction was observed. Qualitative analysis identified 6 themes: Primary Use, Challenges, Impact, Limitations, Feasibility, Acceptability and Usability, and Unmet Needs. Conclusion A pathway of care for retinoblastoma, co-designed by researchers, health professionals and patients, was usable, acceptable, and feasible by caregivers of children with retinoblastoma. While significant effects on communication and physician-patient interaction were not observed, 'legacy building' - documentation of the pathway of care by families for later education of their child - emerged as an unanticipated yet important use of the Retinoblastoma Journey Map.

Caring for a child with retinoblastoma: Experience of Ethiopian parents.

OBJECTIVE: This study explored the lived experience of parents of children with retinoblastoma. DESIGN AND METHOD: A phenomenological qualitative study design was used, and a purposive sampling technique to recruit parents of children with retinoblastoma. Semi-structured interviews were conducted to document the lived experience of participants, who were asked to narrate their experiences caring for a child with retinoblastoma, thinking back to the day they learned about their child's condition, as well as their thoughts about the future. The interviews were conducted in Amharic and Oromo language, and audio recordings were transcribed and translated to English. Data were analyzed using thematic analysis. RESULTS: Thirteen parents (seven mothers, six fathers) participated in the study. Collectively, the children of the participants represented all the stages of the retinoblastoma journey (i.e., diagnosis, treatment, remission, and recurrence). Five major themes emerged from the thematic data analysis: (a) reactions when learning the child's condition; (b) receiving health care; (c) costs of caregiving; (d) support; and (e) uncertainties. CONCLUSION: The lived experiences of parents of children with retinoblastoma revealed a significant mental health and psychosocial burden. The sources of mental distress were found to be complex and varied. Holistic care for retinoblastoma should include programs that address the biopsychosocial needs of caregivers.

Incidence and geographic distribution of retinoblastoma in Ethiopia.

INTRODUCTION: Retinoblastoma is the most frequent intraocular malignancy of the eye in children, occurring in early childhood. Based on global estimates, Ethiopia is expected to observe over 200 new retinoblastoma cases per year, however without a cancer registry, this number is difficult to confirm. Therefore, the goal of the study was to determine the incidence and geographic distribution of retinoblastoma in Ethiopia. METHODS: A retrospective medical chart review of clinically diagnosed new retinoblastoma patients between January 1, 2017 - December 31, 2020, in four public Ethiopian tertiary hospitals was performed. The incidence of retinoblastoma was calculated by a birth-cohort analysis. RESULTS: There were 221 retinoblastoma patients observed in the study period. The incidence of retinoblastoma was found to be 1 in 52,156 live births. Incidence varied among different regions of Ethiopia. CONCLUSION: The incidence of retinoblastoma observed in this study is likely an underestimate. It is possible that patients were undercounted because they were seen outside of the 4 main retinoblastoma treatment facilities included in this facility, or they experienced barriers to accessing care. Our study suggests a need for a nationwide retinoblastoma registry and more retinoblastoma treatment centers in the country.

Referral patterns for retinoblastoma patients in Ethiopia.

BACKGROUND: Increased lag time between the onset of symptoms and treatment of retinoblastoma (RB) is one of the factors contributing to delay in diagnosis. The aim of this study was to understand the referral patterns and lag times for RB patients who were treated at Menelik II Hospital in Addis Ababa, Ethiopia. METHOD: A single-center, cross- sectional study was conducted in January 2018. All new patients with a confirmed RB diagnosis who had presented to Menelik II Hospital from May 2015 to May 2017 were eligible. A questionnaire developed by the research team was administered to the patient's caregiver by phone. RESULTS: Thirty-eight patients were included in the study and completed the phone survey. Twenty-nine patients (76.3%) delayed seeing a health care provider for ≥ 3 months from the onset of symptoms, with the most common reason being the belief that it was not a problem (96.5%), followed by 73% saying it was too expensive. The majority of patients (37/38, 97.4%) visited at least 1 additional health care facility prior to reaching a RB treatment facility. The mean overall lag time from noticing the first symptom to treatment was 14.31 (range 0.25-62.25) months. CONCLUSION: Lack of knowledge and cost are major barriers to patients first seeking care for RB symptoms. Cost and travel distance are major barriers to seeing referred providers and receiving definitive treatment. Delays in care may be alleviated by public education, early screening, and public assistance programs.

EMPOWER Retinoblastoma: Engaging Patient Partners in Solving the Top 10 Priorities for Eye Cancer Research in Canada.

While it is recognized that research priorities should reflect and integrate the perspectives and needs of patients along with those of health professionals and researchers, it remains challenging to actualize such priorities into tangible research projects. Targeted dissemination is required to catalyze research on these priorities. To create awareness of and inspire action toward actualizing the top 10 retinoblastoma research priorities in Canada, Canadian Retinoblastoma Research Advisory Board (CRRAB) members developed a wide range of dissemination tools and processes. These resources, co-produced with patients, were instrumental to CRRAB sharing the top 10 priorities internationally to mobilize action toward solving them.

The Retinoblastoma Research Booklet: A Catalyst for Patient Involvement in Retinoblastoma Research.

Peer-to-peer recruitment efforts are important in generating interest and participation of patients as partners in research but difficult to sustain when face-to-face interactions are limited. The Retinoblastoma Research and You! booklet, co-developed by patients, researchers and health professionals, serves as a guide for patient engagement in research while retaining an element of personalization. The Retinoblastoma Research and You! booklet was developed through two virtual workshops to iterate and finalize the booklet design and content. The booklet outlines how individual patients' lived experiences and skills can influence retinoblastoma research and highlights real-world examples of patient-partnered research activities at different stages of the research process.

Ethical, social, and cultural issues related to clinical genetic testing and counseling in low- and middle-income countries: a systematic review.

PURPOSE: We performed a systematic review of the ethical, social, and cultural issues associated with delivery of genetic services in low- and middle-income countries (LMICs). METHODS: We searched 11 databases for studies addressing ethical, social, and/or cultural issues associated with clinical genetic testing and/or counselling performed in LMICs. Narrative synthesis was employed to analyze findings, and resultant themes were mapped onto the social ecological model (PROSPERO #CRD42016042894). RESULTS: After reviewing 13,308 articles, 192 met inclusion criteria. Nine themes emerged: (1) genetic counseling has a tendency of being directive, (2) genetic services have psychosocial consequences that require improved support, (3) medical genetics training is inadequate, (4) genetic services are difficult to access, (5) social determinants affect uptake and understanding of genetic services, (6) social stigma is often associated with genetic disease, (7) family values are at risk of disruption by genetic services, (8) religious principles pose barriers to acceptability and utilization of genetic services, and (9) cultural beliefs and practices influence uptake of information and understanding of genetic disease. CONCLUSION: We identified a number of complex and interrelated ethical, cultural, and social issues with implications implications for further development of genetic services in LMICs.

Defining Clinical Public Health.

PURPOSE: To solve complex health issues, an innovative and multidisciplinary framework is necessary. The Clinical Public Health (CPH) Division was established at the University of Toronto (UofT), Canada to foster inte-gration of primary care, preventive medicine and public health in education, practice and research. To better understand how the construct of CPH might be applied, we surveyed clinicians, researchers and public health professionals affiliated with the CPH Division to assess their understanding of the CPH concept and its utility in fostering broad collaboration. METHODS: A two-wave anonymous survey of the active faculty of the CPH Division, UofT was conducted across Canada. Wave 1 participants (n = 187; 2016) were asked to define CPH, while Wave 2 participants (n = 192; 2017) were provided a synthesis of Wave 1 results and asked to rank each definition. Both waves were asked about the need for a common definition, and to comment on CPH. RESULTS: Response rates for the first and second waves were 25% and 22%, respectively. Of the six definitions of CPH from Wave 1, "the intersection of clinical practice and public health," was most highly ranked by Wave 2 participants. Positive perceptions of CPH included multidisciplinary collaboration, new fields and insights, forward thinking and innovation. Negative perceptions included CPH being a confusing term, too narrow in scope or too clinical. CONCLUSION: The concept of Clinical Public Health can foster multidisciplinary collaboration to address com-plex health issues because it provides a useful framework for bringing together key disciplines and diverse professional specialties.

Screening for Pineal Trilateral Retinoblastoma Revisited: A Meta-analysis.

TOPIC: To determine the age up to which children are at risk of trilateral retinoblastoma (TRb) developing, whether its onset is linked to the age at which intraocular retinoblastomas develop, and the lead time from a detectable pineal TRb to symptoms. CLINICAL RELEVANCE: Approximately 45% of patients with retinoblastoma-those with a germline RB1 pathogenic variant-are at risk of pineal TRb developing. Early detection and treatment are essential for survival. Current evidence is unclear regarding the usefulness of screening for pineal TRb and, if useful, the age up to which screening should be continued. METHODS: We conducted a study according to the Meta-analysis of Observational Studies in Epidemiology guidelines for reporting meta-analyses of observational studies. We searched PubMed and Embase between January 1, 1966, and February 27, 2019, for published literature. We considered articles reporting patients with TRb with survival and follow-up data. Inclusion of articles was performed separately and independently by 2 authors, and 2 authors also independently extracted the relevant data. They resolved discrepancies by consensus. RESULTS: One hundred thirty-eight patients with pineal TRb were included. Of 22 asymptomatic patients, 21 (95%) were diagnosed before the age of 40 months (median, 16 months; interquartile range, 9-29 months). Age at diagnosis of pineal TRb in patients diagnosed with retinoblastoma at 6 months or younger versus older than 6 months were comparable (P = 0.44), suggesting independence between the ages at diagnosis of intraocular retinoblastoma and pineal TRb. The laterality of intraocular retinoblastoma and its treatment were not associated with the age at which pineal TRb was diagnosed. The lead time from asymptomatic to symptomatic pineal TRb was approximately 1 year. By performing a screening magnetic resonance imaging scan every 6 months after the diagnosis of heritable retinoblastoma (median age, 6 months) until 36 months of age, at least 311 and 776 scans would be required to detect 1 case of asymptomatic pineal TRb and to save a single life, respectively. CONCLUSIONS: Patients with retinoblastoma are at risk of pineal TRb developing for a shorter period than previously assumed, and the age at diagnosis of pineal TRb is independent of the age at diagnosis of retinoblastoma. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) level of evidence for these conclusions remains low.

Feasibility of a school-based vision screening program to detect undiagnosed visual problems in kindergarten children in Ontario.

BACKGROUND: Visual problems can negatively affect visual development and learning but often go undetected. We assessed the feasibility of scaling up a school-based screening program to identify and treat kindergarten children with visual problems. METHODS: We conducted a prospective cohort study offering vision screening to junior (JK) and senior kindergarten (SK) children attending 43 schools in 15 Ontario communities. Screening comprised photoscreeners and tests of visual acuity, stereoacuity and eye alignment. Children who failed any test were referred for a comprehensive eye examination, with treatment as needed (e.g., glasses). RESULTS: Using a passive consent model, 89% of children were screened compared with 62% using an active consent model (p < 0.001). Referral rates to an optometrist varied across schools (mean referral rate for children in JK 53%, range 25%-83%; mean referral rate for children in SK 34%, range 12%-61%). Among 4811 children who were screened, a visual problem was detected in 516 (10.7%), including 164 (3.4%) with amblyopia and 324 (6.7%) with clinically significant refractive errors. For 347 (67.2%) of the children with a visual problem, this was their first eye examination. Rescreening in Year 2 did not lead to detection of additional problems among children who passed screening in Year 1. Regardless of location (child's school or optometrist's office), 1563 (68.9%) of children attended the follow-up optometry examination. Most of the children who were surveyed (291 of 322, 90.4%) indicated that they enjoyed vision screening. INTERPRETATION: Many children in Ontario with a visual problem were not being identified by the status quo in 2015-2017. We found that in-school vision screening with follow-up eye examinations is an effective strategy for identifying at-risk children and placing them in eye care before grade 1.

Patient knowledge, experiences and preferences regarding retinoblastoma and research: A qualitative study.

BACKGROUND: We launched a patient engagement strategy to facilitate research involvement of the retinoblastoma (childhood eye cancer) community in Canada. To inform our strategy, we aimed to uncover the experiences with retinoblastoma, knowledge of retinoblastoma and research engagement among retinoblastoma survivors and parents. METHODS: Focus groups were held in Toronto and Calgary, including both in-person and remote participants (via videoconference). Discussions centred on experience with retinoblastoma, knowledge of the disease and engagement with research. Focus group transcripts were evaluated by inductive thematic analysis. RESULTS: Four focus groups (3 in Toronto, 1 in Calgary) were held with a collective total of 34 participants. Retinoblastoma had a substantial impact on the life of participants, but overall, patients reported being able to adapt and persevere. Experiential knowledge of retinoblastoma was identified as distinct from the theoretical knowledge held by their clinicians. Participants indicated they often acted as a knowledge broker, communicating information about the cancer to their social networks. Participants were willing to engage in research as partners, but recognized barriers such as time and appropriate training. CONCLUSIONS: Patients view their experiential knowledge of retinoblastoma as valuable to improving care and directing research. There is a unique role for research engagement in meeting the educational needs of patients.

Development of a pediatric ophthalmology academic partnership between Canada and Ethiopia: a situational analysis.

BACKGROUND: Educational capacity building in pediatric ophthalmology is necessary to address the burden of childhood blindness in Ethiopia. Residency and fellowship training at Addis Ababa University (AAU) have been enhanced with support from the University of Toronto (UofT), following the established Toronto Addis Ababa Academic Collaboration (TAAAC). Our aim was to assess the feasibility of implementing a pediatric ophthalmology fellowship at AAU with support from UofT, modeled by successful postgraduate medical education within TAAAC. METHODS: A situational analysis, including a needs assessment, was conducted at Menelik II Hospital, Addis Ababa. Staff expertise, equipment and infrastructure were compared to International Council of Ophthalmology fellowship guidelines. Patient volumes were assessed through medical chart review. Local training needs were evaluated. A strategic working meeting facilitated program specification. RESULTS: The faculty consisted of 11 ophthalmologists, including 2 pediatric specialists. Fourteen thousand six hundred twenty-seven medical and three thousand six hundred forty-one surgical pediatric cases were seen in the previous year. A 2-year fellowship incorporating anterior segment, retinoblastoma, strabismus, and retinopathy of prematurity modules was developed. Research collaborations, didactic teaching, and surgical supervision were identified as priorities requiring support. Quality standard indicators included faculty feedback, case log review and formal examination. Telemedicine, development of a larger eye hospital and partnerships to support equipment maintenance were identified as strategies to manage implementation barriers. CONCLUSIONS: The situational analysis provided a way forward for the development of a pediatric ophthalmology fellowship, the first of its kind in Eastern Africa. Learning outcomes are feasible given high patient volumes, qualified staff supervision and sufficient equipment. Strategic partnerships may ensure resource sustainability.

Retinoblastoma, the visible CNS tumor: A review.

The pediatric ocular cancer retinoblastoma is the only central nervous system (CNS) tumor readily observed without specialized equipment: it can be seen by, and in, the naked eye. This accessibility enables unique imaging modalities. Here, we review this cancer for a neuroscience audience, highlighting these clinical and research imaging options, including fundus imaging, optical coherence tomography, ultrasound, and magnetic resonance imaging. We also discuss the subtype of retinoblastoma driven by the MYCN oncogene more commonly associated with neuroblastoma, and consider trilateral retinoblastoma, in which an intracranial tumor arises along with ocular tumors in patients with germline RB1 gene mutations. Retinoblastoma research and clinical care can offer insights applicable to CNS malignancies, and also benefit from approaches developed elsewhere in the CNS.

Parental coping with retinoblastoma diagnosis.

OBJECTIVE: To characterize coping and distress among parents of children with retinoblastoma, and to uncover their association with perceived health literacy, self-efficacy, and social support. METHODS: This was a cross-sectional study performed in the retinoblastoma clinics of Beijing Children's Hospital, Jilin Eye Hospital and Changchun Hospital in China. Parents of children with retinoblastoma (n = 104) completed a print Mandarin language questionnaire consisting of four sections: (i) demographic information, (ii) mini-mental adjustment to cancer scale, (iii) hospital anxiety and depression scale, and (iv) perceived health literacy, self-efficacy, and social support scales. Scores were tabulated for each measure and analyzed by bivariate correlation. RESULTS: Moderate anxiety affected 59.2% of parents, and 77.7% experienced low, moderate, or high levels of depression. Combined anxiety and depression was positively correlated with helplessness/hopelessness (R = 0.42, p < .01) and anxious preoccupation (R = 0.247, p < .05), and negatively correlated with perceived self-efficacy (R = -0.228, p < .05). Perceived social support from a partner was negatively correlated with depression (R = -0.207, p < .05) and helplessness/hopelessness (R = -0.271, p < .01). CONCLUSIONS: Knowledge of how parents cope with their child's cancer diagnosis can help healthcare teams understand how best to support their psychosocial needs.

Clinical and genetic associations for carboplatin-related ototoxicity in children treated for retinoblastoma: A retrospective noncomparative single-institute experience.

BACKGROUND: Children with retinoblastoma treated with carboplatin chemotherapy risk moderate to severe, irreversible hearing loss. Based on published evidence, we hypothesized that ototoxicity risk is associated with clinical parameters and variants in candidate genes in drug metabolism pathways (methyltransferases [thiopurine S-methyltransferase, TPMT] and [catechol-O-methyltransferase, COMT], and drug transporter ABCC3). PROCEDURE: We retrospectively reviewed clinical records of patients with retinoblastoma treated with carboplatin chemotherapy regarding age (at diagnosis and chemotherapy initiation), chemotherapy sessions (cycles number, drug doses, and cumulative carboplatin dose), and hearing loss (defined as ototoxicity ≥grade 2 by at least one classification system). Blood samples were genotyped for genetic variants in TPMT (rs12201199, rs1800460), COMT (rs4646316, rs9332377), and ABCC3 (rs1051640) by quantitative PCR and confirmed by allele-specific PCR. Univariate statistical tests, receiver-operating characteristic analysis, and Kaplan-Meier curves were used to examine the association between hearing loss, clinical factors, and variants in candidate genes. RESULTS: Audiometric data and stored DNA were available for 71 patients with retinoblastoma (88% carried an RB1 pathogenic variant allele). Median carboplatin cumulative dose was 1,400 mg/m2 (260-5,148 mg/m2 ). Ototoxicity occurred in 18 patients (25%), strongly associated with age at diagnosis (P = 0.01) and age at chemotherapy initiation (OR = 4.99, P = 0.008). The highest likelihood ratio of hearing loss was associated with chemotherapy initiation <4.25 months of age. Ototoxicity was not associated with any tested genetic variants. CONCLUSIONS: We observed a 25% prevalence of ototoxicity in patients with retinoblastoma treated with carboplatin, higher than previously published. Age at chemotherapy initiation was associated with carboplatin-induced ototoxicity, with children <4.25 months of age at highest risk.

"Where Does it Come from?" Experiences Among Survivors and Parents of Children with Retinoblastoma in Kenya.

Genetic testing and counseling have become integral to the timely control of heritable cancers, like the childhood eye cancer retinoblastoma. This study aimed to determine attitudes, knowledge and experiences related to retinoblastoma genetics, among survivors and parents of children with retinoblastoma in Kenya. This qualitative study used focus groups as the primary data collection method, coupled with a brief demographic questionnaire. Study settings were Kenyatta National Hospital and Presbyterian Church of East Africa Kikuyu Hospital. Thematic analysis was used to identify key themes. Thirty-one individuals participated in five focus groups. Two main concepts emerged: (1) the origins of retinoblastoma are unclear, and (2) retinoblastoma is associated with significant challenges. The lack of clarity surrounding the origins of retinoblastoma was linked to limited knowledge of retinoblastoma genetics, and limited genetic counseling delivery and uptake. The challenges associated with retinoblastoma were discussed in terms of the impact of the diagnosis on individuals and families, and unmet healthcare needs related to the diagnosis. Next steps will incorporate these findings to develop evidence-informed and accessible cancer genetic services in Kenya.

Prenatal versus Postnatal Screening for Familial Retinoblastoma.

PURPOSE: To compare overall outcomes of conventional postnatal screening of familial retinoblastoma and prenatal RB1 mutation identification followed by planned early-term delivery. DESIGN: Retrospective, observational study. PARTICIPANTS: Twenty children with familial retinoblastoma born between 1996 and 2014 and examined within 1 week of birth. METHODS: Cohort 1 included spontaneously delivered neonates examined within 1 week of birth and confirmed postnatal to carry their family's RB1 mutant allele. Cohort 2 included infants identified by amniocentesis to carry their family's RB1 mutant allele, and therefore scheduled for early-term delivery (36-38 weeks' gestation). Treatment for retinoblastoma was performed at the Hospital for Sick Children, Toronto, Canada. MAIN OUTCOME MEASURES: Age at first tumor in each eye, eye stage, treatments given, ocular salvage, treatment success (defined as avoidance of enucleation, external-beam irradiation, or both), visual outcome, number of anesthetics, pregnancy or delivery complications, and estimated treatment burden. RESULTS: Vision-threatening tumors were present at birth in 4 of 8 infants in cohort 1 and in 3 of 12 infants in cohort 2. Eventually, all infants demonstrated tumors in both eyes. At the first treatment, 1 of 8 infants in cohort 1 had eyes in stage cT1a/cT1a or cT1a/cT0 (smallest and least vision-threatening tumors), compared with 8 of 12 infants in cohort 2 (P = 0.02). Null RB1 germline alleles induced earlier tumors than low-penetrance alleles (P = 0.03). Treatment success was achieved in 3 of 8 children in cohort 1 compared with 11 of 12 children in cohort 2 (P = 0.002). Acceptable vision (better than 0.2 decimal) was achieved for 8 of 16 eyes in cohort 1 compared with 21 of 24 eyes in cohort 2 (P = 0.014). Useful vision (better than 0.1, legal blindness) was achieved for 8 of 9 children in cohort 1 compared with 12 of 12 children in cohort 2. There were no complications related to early-term delivery. Median follow-up was 5.6 years, cohort 1 and 5.8 years, cohort 2. CONCLUSIONS: When a parent had retinoblastoma, prenatal molecular diagnosis with early-term delivery increased the likelihood of infants born with no detectable tumors, better vision outcomes, and less invasive therapy. Prenatal molecular diagnosis facilitates anticipatory planning for both the child and family.

Achieving optimal cancer outcomes in East Africa through multidisciplinary partnership: a case study of the Kenyan National Retinoblastoma Strategy group.

BACKGROUND: Strategic, interdisciplinary partnerships are essential to addressing the complex drivers of health inequities that result in survival disparities worldwide. Take for example the aggressive early childhood eye cancer retinoblastoma, where survival reaches 97 % in resource-rich countries, but is as low 30 % in some resource-limited nations, where 92 % of the burden lies. This suggests a need for a multifaceted approach to achieve a tangible and sustainable increase in survival. METHODS: We assembled the history the Kenyan National Retinoblastoma Strategy (KNRbS), using information documented in NGO reports, grant applications, news articles, meeting agendas and summaries. We evaluated the KNRbS using the principles found in the guide for transboundary research partnerships developed by the Swiss Commission for Research Partnerships with Developing Countries. RESULTS: A nationally co-ordinated approach drawing input and expertise from multiple disciplines and sectors presented opportunities to optimise cure of children with retinoblastoma. Annual meetings were key to achieving the over 40 major outputs of the group's efforts, related to Awareness, Medical Care, Family Support and Resource Mobilization. Three features were found to be critical to the KNRbS success: multidisciplinarity, consistency and flexibility. CONCLUSION: The KNRbS has achieved a number of key outputs with limited financial investment. As a partnership, the KNRbS meets most of the criteria identified for success. Challenges remain in securing the long-term sustainability of its achievements. Elements of the Kenyan National Retinoblastoma Strategy may be useful to other developing countries struggling with limited survival of retinoblastoma and other cancers or rare diseases.

Maintaining Research Integrity While Balancing Cultural Sensitivity: A Case Study and Lessons From the Field.

Contemporary emphasis on creating culturally relevant and context specific knowledge increasingly drives researchers to conduct their work in settings outside their home country. This often requires researchers to build relationships with various stakeholders who may have a vested interest in the research. This case study examines the tension between relationship development with stakeholders and maintaining study integrity, in the context of potential harms, data credibility and cultural sensitivity. We describe an ethical breach in the conduct of global health research by a arising from the ad-hoc participation of a community stakeholder external to the visiting research group. A framework for reflection is developed from a careful examination of underlying factors and presented with a discussion of consequences and mitigation measures. This framework aims to present lessons learned for researchers working abroad who might face similar situations in their work.

Challenges faced by multidisplinary new investigators on addressing grand challenges in global health.

BACKGROUND: The grand challenges approach aims to spark innovative and transformative strategies to overcome barriers to significant global health issues. Grand Challenges Canada endorses an 'Integrated Innovation™' approach that focuses on the intersection of scientific/technological, social and business innovation. In this article we explore themes emerging from a dialogue between the authors, who are multidisciplinary recipients of the 'Rising Stars in Global Health' award from Grand Challenges Canada, regarding benefits of engaging in integrated innovation research, and recommendations for how this approach may develop in the future. DISCUSSION: Our dialogue followed a semi-structured interview format that addressed three topics: 1) reflections on applying an Integrated Innovation™ approach for global health; 2) thoughts on participation in the Grand Challenges 2012 meeting; and 3) authors' visions of Grand Challenges Canada and the Grand Challenge movement towards 2020. The dialogue was transcribed verbatim and we used thematic analysis techniques to identify, analyze and report themes in the data. Benefits of working using the Grand Challenges approach centered on two themes: a) the potential for scientific breakthrough and b) building interdisciplinary collaborations and a community of scholars. Challenges and opportunities for Grand Challenges in moving forward included: a) capacity building, particularly regarding Integrated Innovation™ and scale-up planning; b) interdisciplinary and international mentorship for new investigators; and c) potential for future commercialization. CONCLUSIONS: Our discussion highlighted that Integrated Innovation™ offers the opportunity to develop new theories, methods and approaches to global health while simultaneously fostering a collaborative spirit grounded in international, interdisciplinary collaborations. However, the arguable over-emphasis on corporatization poses a major challenge for new investigators. We propose a more balanced way forward that can harness technology to foster mentorship across time and space to support the development of such skills and ideas among new investigators.