Integrating Real-World Evidence (RWE) in Oncology Drug Regulation: A Comparative Analysis of CDSCO and Health Canada

RESEARCH ARTICLE Am. J. PharmTech Res. 2025; 15(05) ISSN: 2249-3387 Please cite this article as: Kumar A et al., Integrating Real-World Evidence (RWE) in Oncology Drug Regulation: A Comparative Analysis of CDSCO and Health Canada. American Journal of PharmTech Research 202 5 . Integrating Real-World Evidence (RWE) in Oncology Drug Regulation: A Comparative Analysis of CDSCO and Health Canada Ashok Kumar P*, Sai Sivani Togati, Sara Jabeen, Sahana CM, Siddesh KS, Hemanth GR Department of Regulatory Affairs, Sree Siddaganga College of Pharmacy, 1st Left Cross, 3rd Block, Mahalakshmi Nagar, Near Railway Gate, 80 feet Road, Batwadi, Tumkur-572103, Karnataka, India. ABSTRACT Cancer remains a major global health challenge, necessitating continuous innovation in oncology therapeutics. While randomized controlled trials (RCTs) are the traditional gold standard for evidence generation, they often lack applicability to diverse real-world populations. This has fuelled growing interest in incorporating Real-World Evidence (RWE), derived from Real-World Data (RWD), into regulatory decision-making processes, especially in oncology. This study aims to compare how RWE is integrated into oncology drug regulation by two key regulatory bodies, Health Canada and India’s Central Drugs Standard Control Organization (CDSCO), in order to identify lessons and opportunities that can support India's evolving regulatory framework. A qualitative comparative analysis was conducted using regulatory documents, guidance frameworks, and real-world case examples. Canada’s CanREValue initiative was explored in depth, alongside an assessment of India’s emerging digital health infrastructure and policy efforts. Health Canada has established a mature RWE framework supported by multi-stakeholder collaborations and pilot projects, facilitating dynamic regulatory decisions in oncology. In contrast, CDSCO is in the early stages of RWE adoption, with limited formal guidance. However, initiatives like the Ayushman Bharat Digital Mission (ABDM) and national health registries offer promising pathways. Canada’s regulatory progress offers valuable insights for India. Strengthening digital infrastructure, developing national RWE frameworks, and fostering collaboration could transform India’s oncology regulatory ecosystem. This study highlights the potential of RWE to improve evidence-driven decision-making and enhance access to cancer therapies. Keywords: Real-World Evidence, Oncology, Drug Regulation, CDSCO, Health Canada, CanREValue *Corresponding Author Email: [email protected] Received 02 August 2025, Accepted 26 August 2025 Journal home page: http://www.ajptr.com/ Kumar et. al., Am. J. PharmTech Res. 2025;15(05) ISSN: 2249-3387 www.ajptr.com 178 INTRODUCTION Real-World Evidence (RWE) is derived from Real-World Data (RWD), this phase involves the application of the Real-World Data to the Real-World Evidence and consists of the patient health data that is regularly gathered without randomized control trials (RCTs). Other sources that add to this pool of data include electronic health records, insurance claims, disease registries, and patientreported outcomes. In contrast to some traditional clinical trials, RWE considers the dynamics of different patient groups and clinical practice at the population level and long-term outcomes of treatments in real-life scenarios. As the scope of RCT undergoes and continues to expand limitation due to cost, time-consuming issues, and inability to explore and test restricted segments of the population, regulatory bodies and other healthcare stakeholders are starting to use RWE as a supplementary source of evidence. Managing rare cancers There is much potential to use RWE to inform drug approvals, label expansion, and postmarketing surveillance in oncology, where decisions need to be made quickly and where there is generally little available trial evidence. The world is developing towards regulation to adjust to this change. Whereas countries such as the United States FDA and European Medicines Agency (EMA) have implemented guidelines on the utilization of RWE, others such as Canada and India are still in different phases of formalizing its application. Canadian regulatory system has launched specialized programs such as CanREValue whereas India is at starting points of the digital health revolution but is actively interested in the use of RWD to support regulatory and clinical decision-making. Overview of Health Canada The federal department that is mandated with the health and safety protection and improvement of Canadian people is the Health Canada. It is the main regulatory body of drugs, biologics and medical devices as well as of other products that affect health, working in the frame of Food and Drugs Act and other important legislative platforms. The vision of Health Canada focuses on a strong, transparent, and evidence-based regulatory policy which aims to maintain a healthier product in the market, in terms of quality, efficaciousness, and security of the therapeutic products which enter its frontier. The process of drug approval drug in Canada is a tiresome process that is encompassed of several stages. First, the drug developers can have pre-submission conferences where the expectations and requirements can be explained. After this, the developer will proceed to make the New Drug Submission (NDS) with full illustration of information relative to the safety, efficacy and quality Kumar et. al., Am. J. PharmTech Res. 2025; 15(05) ISSN: 2249-3387 179 www.ajptr.com on the product. The submission is also subject to the intensive scientific assessment by the pertinent directive (TPD or BGTD) and this process may incorporate consultations to the expert advisory committee in cases where it seems necessary. Should the review exhibit a favorable outcome, Health Canada grants a Notice of Compliance (NOC), which allows entry in the market, and gives the drug a Drug Identification Number (DIN), a formal approval. This multiple layered regulatory model provides a balance between giving access to new therapies and safeguarding the health of the population by scientific rigor. Real-World Evidence (RWE) is gaining importance in the oncology drug regulation. Although conventionally RWE is used as a supplement to post-market safety surveillance, Health Canada is starting to embrace the use of RWE in regulatory decision-making especially in post-market settings or label extension in a rare cancer population. One such application is in post-approval monitoring of safety in immune check point inhibitors like nivolumab (Opdivo) and pembrolizumab (Keytruda). These medicines were approved by NOC/c on various indications, and the effectiveness and safety of the related medicine were also reinforced by real-world databases of various types of patient populations in non-controlled conditions. Figure 1: Health Canada’s Regulatory Structure Real-World Evidence (RWE) is gaining importance in the oncology drug regulation. Although conventionally RWE is used as a supplement to post-market safety surveillance, Health Canada is starting to embrace the use of RWE in regulatory decision-making especially in post-market settings or label extension in a rare cancer population. One such application is in post-approval monitoring of safety in immune check point inhibitors like nivolumab (Opdivo) and pembrolizumab (Keytruda). These medicines were approved by NOC/c on various indications, and Kumar et. al., Am. J. PharmTech Res. 2025;15(05) ISSN: 2249-3387 www.ajptr.com 180 the effectiveness and safety of the related medicine were also reinforced by real-world databases of various types of patient populations in non-controlled conditions. Furthermore, Health Canada, in its new regulatory strategy, is eager to work with its international partners including the U.S. FDA, European Medicines Agency (EMA) and International Council for Harmonization (ICH) to harmonize the standards and share the data especially oncology drugs that are being developed and introduced in different countries and regions. Such collaborations also increase the integration of RWE by establishing unified critiques and procedures of evidence assessment. CanREValue initiative Real-world Evidence for Value in Cancer (CanREValue) Initiative is a national coordinated activity to build a strong system of implementation of the Real-World Evidence (RWE) in Canadian drug lifecycle in the oncology space. This initiative, which began its work in 2017 and is headed by ICES (formerly the Institute for Clinical Evaluative Sciences) was a reaction to the growing interest in evidence on the clinical and economic performance of high-cost oncology medications in the real-world. Very often, cancer treatments are registered with a small amount of evident trial results, sometimes even under a conditional framework like the Notice of Compliance with Conditions (NOC/c) which implies that substantially not much can be known about long-run effectiveness, safety and cost-efficiency. In this respect, CanREValue was conceptualized as developing an infrastructure to produce and integrate RWE at numerous thresholds in the life cycle of a drug, most especially its post-market phase. The main goal of CanREValue is working out a pan-Canadian system enabling consistent creation and utilization of RWE in HTA (Health Technology Assessment), pricing and reimbursement policy and reappraisal of oncology drugs. This does not only consolidate improved clinical outcomes but also makes healthcare budgets sustainable, particularly, as the costs of emerging novel targeted and immuno-oncology agent surge. To accomplish this, five working groups are set where the roles of developing particular elements of the framework are distributed. The essence of CanREValue is that RWE should be fit-for-purpose. In contrast to randomized controlled trials (RCTs), real-world data (RWD) sources like cancer registries, administrative claims, and EMRs do not contain enough quality and complete data. Thus, CanREValue highlights legible rules about the design of studies, protocol disclosure, and peer-review review of RWE reports. The potential of this method has been proven during pilot projects, e.g., the exploration of the survival rates and the treatment patterns of immunotherapy agents in the various provinces. Kumar et. al., Am. J. PharmTech Res. 2025; 15(05) ISSN: 2249-3387 181 www.ajptr.com During the last few years, Canada has improved remarkably when it comes to codifying the use of Real-World Evidence (RWE) utilized in drug assessment. With the mounting pressure to bring novel therapies to market at an enhanced pace and, particularly, in oncology, the necessity of wellorganized, transparent, and scientifically sound systems of RWE has significantly increased. Being aware of this, Health Canada, as well as CADTH (Canadian Agency for Drugs and Technologies in Health), developed guidance documents and participated in pilot projects that examine how RWE can effectively be used in the regulatory and health technology assessment (HTA) context. In 2019, Health Canada began a consultation on RWE by issuing its discussion paper entitled: Real-World Evidence: Informing Regulatory Decision Making, which set out the various circumstances where RWE might assist in a regulatory decision to approve drugs, including new uses and safety monitoring (after the drug is on the market). The document also highlighted that despite the fact that RCTs are the gold standard as regards to the establishment of efficacy, RWE could help add to the information regarding these fields, by being able to determine if the long-term developments of the results are commendable, how rare type of adverse events occur and also how effective the given is on wider and a more diverse population. The approach adopted by the health Canada parallels international developments and is comparable to the initiatives of the FDA in the RWE Framework and the Adaptive pathways developed by the European Medicines Agency. Subsequently, Health Canada launched regulatory pilot projects with industry stakeholders trying using real-world data in new indications and changes to labels. These pilots tested real-world end points, approaches to data curation and the acceptability of study designs -- including retrospective cohort analyses of provincial administrative health data. Such pilots created a framework that will continue to be used in further RWE opportunities application with regulatory submission, creating capacity internally in the agency and expectations in the industry. Concurrently, CADTH has released a reassessment RWE guidance, especially in its post-market drug evaluation program. During 2021 CADTH published a framework of the Use of Real-World Evidence to Support Post-Market Drug Reassessment, whereby payers can reconsider funding decisions. This applied especially to oncology where, the first funding is usually made on uncertain grounds and has to be reviewed after some time. The areas of importance that CADTH RWE framework stress is the sources of data required, analysis strategy, governance, and costeffectiveness and clinical impact decision-level thresholds. Kumar et. al., Am. J. PharmTech Res. 2025;15(05) ISSN: 2249-3387 www.ajptr.com 182 Figure 2: Canada’s Journey in RWE On top of these regulatory and HTA activities, the CanREValue Collaboration has had several RWE pilot studies with the support of provincial cancer agencies. This group of pilots tested the outcomes of the active therapy and use of many immuno-oncology agents in the non-small cell lung cancer (NSCLC). The researchers could use population-based cancer registries, pharmacy claims, and mortality databases to evaluate such outcomes as overall survival, time of disrupting treatment, and the utilization of healthcare resources beyond trials. A well-known CanREValue pilot has employed real-life data of Ontario and British Columbia to study post-market performance of nivolumab within patients with advanced NSCLC. This paper gave us some idea of the way the drug worked in older people and in individuals with multiple medical conditionstwo groups not usually inculcated into clinical trials. Findings were in agreement with the RCT study and further supports the evidence base to reimburse ongoing benefits in the public plans. Also, the study showed that it is possible to perform pan-Canadian RWE studies with harmonized research strategies and connections between data resources, which opens a gateway to national-level evaluations. The other example is that of the reassessment of palbociclib in metastatic breast cancer. First sanctioned via a conditional NOC/c pathway, earlier clinical experience led to follow-up HTA and funding modifications in a number of provinces as a result of real-world data. The experiences of these types of RWE were used to explain the selection and modification of treatment criteria, dosage adjustments, and monitoring. This contributes to increasing the clinical value and costeffectiveness. Overview of CDSCO(India) Kumar et. al., Am. J. PharmTech Res. 2025; 15(05) ISSN: 2249-3387 183 www.ajptr.com The Central Drugs Standard Control Organization (CDSCO) is the top agency in India that administers health care products and medical equipment. CDSCO operates under the Ministry of Health and Family Welfare and is the National Regulatory Authority (NRA) responsible in the safety, efficacy, and quality of medical products in the Indian markets. It collaborates with State Drug Control Departments that allows making a dual regulation type where there is balance between central drug approvals, and decentral implementation and enforcement. Under Drugs Controller General of India (DCGI), CDSCO deals with:  New drug approval and clinical trials.  Control of import and export of drugs and cosmetics.  Regulation of biologics, vaccines and medical products.  BA/BE data evaluation.  Implementation of pharmacovigilance schemes on post market safety surveillance. CDSCO is functioning under legal framework of:  Drugs and cosmetics act, 1940  Drugs and Cosmetics Rules 1945  And just recently the New Drugs and Clinical Trials Rules, 2019 (NDCTR) These regulations give an elaborate procedure on how the approval of new drugs, clinical trials and investigational new drugs (INDs) are to be facilitated adding clarity to the specifications of ethics committee duties, responsibility of sponsor and commitments after marketing. The regulatory provisions are also issued as regulatory guidance documents and standard operating procedures (SOPs) by CDSCO in order to facilitate quicker and more transparent interactions on the regulatory front. It regularly works with other regulatory bodies across different countries including the US FDA, EMA, and WHO in mutual harmonization initiatives within ICH (International Council for Harmonization) and PIC/S. The CDSCO operates on two levels, the central office in New Delhi, with support staff in:  6 Zone Offices (Mumbai, Kolkata, Chennai, Ghaziabad, Hyderabad, Ahmedabad)  4 Sub-Zonal offices  13 Port Offices  7 Central drug testing laboratories Kumar et. al., Am. J. PharmTech Res. 2025;15(05) ISSN: 2249-3387 www.ajptr.com 184 Figure 3: India’s Drug Regulatory Structure Oncology is one such area of therapy in which quick access to new therapies matters a great deal. The increased burden of cancer in India, approximated at a rate of more than 1.5 million new cases per year (ICMR, 2021), has already resulted in the need to embrace more accommodating regulatory framework to satisfy its treatment needs. Although the agency is still concerned in making drugs in oncology and rare diseases available when and where they are needed, it also has a sound pharmacovigilance system in the form of Pharmacovigilance Program of India (PvPI) facilitated by the Indian Pharmacopoeia Commission (IPC). But the recent activity of post-marketing surveillance is rather done on the grounds of safety (e.g., Serious Adverse Event [SAE] reporting, periodical updates of safety information) than on realistic effectiveness. RWE Regulatory Decision-Making in India Use of RWE in regulatory decisions in India is young. The regulatory authorities, US FDA, Health Canada and European Medicines Agency (EMA) have worldwide implemented regulatory pathways to include RWE in other aspects of drug life cycle, including pre-approval analysis and prioritized access, post-market review and policy update. Conversely, the Indian regulatory environment, led by the Central Drugs Standard Control Organization (CDSCO) is yet to incorporate RWE as an organized aspect of its decision-making and regulatory functions. Although India is not yet equipped with a specific RWE policy or framework, some specific activity performed by regulating is indirectly associated with aspects of real-world data. These Kumar et. al., Am. J. PharmTech Res. 2025; 15(05) ISSN: 2249-3387 185 www.ajptr.com mainly incorporate post-marketing surveillance (PMS), pharmacovigilance, and a family obligation Phase-IV studies mainly on drugs either receiving a waiver of a local clinical trial, or those approved under an accelerated course. To be specific, within the sphere of oncology CDSCO sometimes allows the marketing of drugs already approved in other jurisdictions with open regulatory practices, such as the United States of America or the European Union, without local testing in India. The regulatory body in such instances normally puts obligation on sponsor to carry out post marketing studies to track safety of the Indian population. These analyses are however more likely to study negative side effects of the drugs as well as safety hazards but would not take into account the overall effectiveness or comparison with other outcomes which RWE endeavors to document. Despite the fact that real-world data are being generated in India based on hospital-based registries, electronic health records (EHRs), and observational studies, yet the information is not being utilized by CDSCO in a regulatory capacity in a regular manner. As an illustration, all the major cancer hospitals in the country, All India Institute of Medical Sciences (AIIMS), Tata Memorial Hospital, and privately owned networks, Apollo and Manipal administer retrospective and prospective observational research. Such studies can usually offer useful knowledge on the performance of drugs, patient compliance, and treatment outcomes in a real-life scenario. The regulatory value of these data, however, is limited because it has no process in CDSCO to formally review this evidence or use it in making decisions when approving drugs, updating labels or bargaining drug prices. However, change dynamic gives us relevance of future integration. The introduction to the National Digital Health Mission (NDHM) in Ayushman Bharat Digital Mission will produce a common digital health system nationwide. This entails both patient-specific health IDs as well as the patient EMR systems and data-sharing systems, all of which have the potential of establishing a large-scale RWE generation. There is further a National Cancer Registry Program (NCRP) sponsored by the Indian Council of Medical Research (ICMR) providing disease-specific information which, when extended and joined to therapeutic results, these may become a significant information source to oncology-related RWE. Along with that, there is an increasing sense of appreciation about the usefulness of RWE in supplementing clinical trial evidence in an internationally diverse and high-population country such as India. There are many patient subgroups included in the trials condition that are still excluded in real-world data, including seniors, those who have comorbidities, or patients in a rural