In the current analysis, we found that there is a high disparity or difference or variation across geographic locations in India in accessing clinical trials by the cancer patients, particularly in four common malignancies, including breast cancer, cervical cancer, head and neck cancer and lung cancer.
There is nearly a thousandfold difference in the SSY between the states with the smallest and the highest SSY in therapeutic interventional studies. States in the North-eastern part of the country have fewer available clinical trial slots for patients. Tobacco associated cancers account for about 1/3rd of all cancers in India (8). It is, therefore, surprising to see that active intervention studies investigating a preventive approach were being conducted in only two states in the country. Across the nation, however, access to cancer clinical trials remains poor. Even in the state with the highest SSY of 55.21 per 1,000 incident cases (Delhi), by definition, a clinical trial slot is available for only 5.5% of the new cancer patients diagnosed every year in the state. Note there are two union-territories with a higher SSY - Chandigarh with SSY of 296 per 1,000 incident cases and Puducherry with SSY of 141 per 1,000 incident cases.
The disparity is even starker when cancer sites are considered. For example, therapeutic interventional studies are available for Brain tumour patients in only two states in the country. The true magnitude of disparity is likely to be magnified by the fact that most of the cancer centres in which these studies are available are located in urban areas of the country, in addition to the other barriers to research (14–16).
The reasons behind the disparity are possibly multi-fold and out of the scope of the present analysis. As SSY is a state-level metric, the total number of values available is limited to permit an adequate regression model. Unfortunately, district-level data of cancer incidence is not available in India, which would have permitted evaluation of the influence of the selected indicators on the disparity in access. One factor that shows a relationship is the per-capita state net domestic product, where the higher per-capita net domestic product seems to be associated with a higher SSY. State literacy rate also seems to have a monotonous relationship. However, given the small number of states and the presence of outliers, a definite relationship cannot be established. Further exploration of funding sources also reveals that disparity persists across funding sources also (Figure 7). Government-funded therapeutic interventional studies were available in only six states (6, 16%). Interestingly intra-mural funded studies seem to be spread out more uniformly across the country.
The association between the incidence to mortality ratio and the SSY is intriguing, but a causative role cannot be attributed. Given the overall low number of cancer clinical trial seats, it is unlikely that participation in clinical trials itself is responsible for the improved outcomes in the states with higher SSY. Better healthcare infrastructure and facilities in these states that facilitate the conduct of cancer clinical trials may be responsible for such an association with improved incidence mortality ratio.
Inequities in geographical access to cancer care have been demonstrated to be associated with increasing stage at diagnosis, poor compliance with treatment, worse outcomes and quality of life (17). Syed et al. have additionally shown that such disparities disproportionately affect minorities and those with lower incomes (18). Additionally, this is a barrier to fair representation in clinical trials. In a statewide survey of oncology patients in Pennsylvania, only 37% of patients indicated that they would be willing to travel in order to participate in a clinical trial (19). Similar findings were demonstrated by Lara et al. in a prospective study of patients at the University of California Davis Cancer Center, where the distance from the cancer centre was the second most common reason cited for not participating in a clinical trial (20). Whether this is true for Indian patients needs to be investigated further.
A recent paper demonstrated that unequal geographic access to clinical trials exists even in the USA (median clinical trial seats per 1,000 residents 0.64, IQR: 0.25 - 1.01) (21). In an analysis by Galsky et al., it was found that 45.6%, 50.2%, 52.2% and 38.4% of the patients with metastatic breast, prostate, colorectal and non-small cell lung cancers, respectively, will have to drive more than 1 hour to access a clinical trial site (22). It should be noted that Indian cancer patients routinely travel much longer distances to avail quality cancer care (23,24). Carneiro et al. have shown that the number of interventional cancer clinical trials per 100000 population in the country ranges between 0.14 - 10.7 in Europe (25). In India, where we identified only 132 open interventional clinical trials, the number of open interventional trial entries per 100000 population is only 0.01 (for a population of 1.3 billion).
The strengths of this study are a detailed evaluation of the intra-state geographic disparity in access to clinical trials using publicly available high-quality data. To our knowledge, this is the first analysis of this kind. Disparities exist across study types and are magnified when specific cancer types are evaluated.
Our study has several limitations. First, our analysis is limited to studies registered in the Clinical Trial Registry of India. While it is likely that we may have information about a larger number of trials if other registries we chose to restrict our search to CTRI only as it is a legal requirement for all regulatory, clinical trials as per the CDSCO since 15th June 2009 (26,27). Second, geographic access has been estimated based on state, while clinical trials are conducted in specific institutes. Unfortunately, institute wise cancer statistics are not available in the public domain for all cancer institutes across the country. However, the geographic disparity will likely be more magnified if an institute level analysis is conducted as the majority of cancer centres in India are located in urban areas. Similarly, as we have considered only incident cases in the denominator, which is likely to be highly conservative as the prevalence of several cancers is likely to be higher than the incidence. Third, we have used the incidence data from two sources which rely on population-based and hospital-based cancer registries for estimates of new cancer case burden. However, registry coverage across the nation is not homogenous. Finally, we restricted our analysis to open trials where studies whose planned duration was such that they should have closed by 1st January 2020 were considered as completed. It is likely that some of these trials may still be open to recruitment.