Real-World Evidence Studies in Oncology Therapeutics: Hope or Hype?

Randomized controlled trial (RCT) remains a gold standard in evidence-based medicine for assessing the efficacy and safety of cancer therapies. However, due to some inherent methodological limitations of RCT, such as stringent inclusion criteria, highly specific treatment, ethical and scientific compromise in rare cancer, and inability to adequately assess safety, real-world evidence (RWE) has been adjudged as a suitable option to complement data obtained from RCT. Moreover, in the context of cancer therapeutics, few notable merits pertain to developing a novel product for rare cancer subtypes, establishing new indications for already approved drugs, optimization of treatment regimen and sequence, a better description of long-term safety, and supporting the reimbursement-related decision. However, the implementation of RWE for the aforementioned purposes will be limited by various challenges, especially in the context of developing economies such as India. Special attention should be given to the availability of data, maintaining the quality standard, and establishing stringent regulations for privacy and security along with active regulatory engagement with relevant stakeholders. Such activities will be key to facilitating the use of RWE in cancer therapeutics.

Advances in orphan drug development: Time to change the status and stereotype.

Rare diseases remain a challenge for many of the countries in the world. The millions of people collectively suffering from rare diseases, in the context of raging COVID-19 pandemics globally, require an innovative and recent solution from different stakeholders. Regulatory bodies such as the Food and Drug Administration and the European Medicines Agency have come up with many different approaches including financial assistance to prompt drug development and approval. Novel approaches pertinent to clinical trials of such drugs such as patient centricity, early interaction with regulatory bodies, and establishing clinical outcome of interest have been experimented. Various international organizations including cross-country collaborators have initiated various projects or consortiums to bridge the gap between knowledge and practice. The challenges remain more pivotal in developing countries such as India, which has adopted few noteworthy initiatives by involving relevant stakeholders in the presence of limited resources, infrastructures, and a nascent regulatory framework. Therefore, it is imperative to revisit the key aspects of orphan drug development to fulfill the unmet needs of such patients suffering from various rare diseases.

Digital clinical trial: A new norm in clinical research.

The advent of digital technologies has been well blended with every aspect of human lives. Despite not being a new concept, the adoption of digital health technologies in clinical research, i.e., digital clinical trial has not been utilized extensively. However, with the prevailing COVID-19 pandemics, such transformation in clinical trial seems imminent. Few components of a trial such as consent, remote site monitoring, recruitment process which can be modified through digital technologies, are further specified by the regulatory authorities such as FDA and EMA. However, such novel method cannot be implemented without facing any limitations. All stakeholders pertinent to virtual clinical trial including the provider of digital technologies should align themselves with the patient-centric approach to propagate this concept. It is expected that such a transition is well accomplished and adopted by the sponsors without any compromise in scientific as well as ethical standard.

Accelerated drug approvals in oncology: Pros and cons.

The inevitable surge of the accelerated approval process, especially for oncology drugs, has been a success story. However, the use of surrogate end-points and its validation has been debatable over the years. Over the years, US Food and Drug Administration has been rigorously working for the validation of these end-points to capture the real clinical benefit and appropriateness of clinical study designs. However, the high cost imposed by the manufacturer attributed to the faster drug access can be prohibitive and well undermine the whole process. We discuss issues that must be addressed and solved accordingly for managed care in oncology.

Advances in Vasodilatory Shock: A Concise Review.

Vasodilatory shock is a critical manifestation of cardiovascular failure. There is uncontrolled vasodilation and vascular hyporesponsiveness to endogenous vasoconstrictors, causing the failure of physiologic vasoregulatory mechanisms. Unfortunately, only few randomized studies exist to guide clinical management and hemodynamic stabilization in patients who do not respond to the standard approach of managing vasodilatory shock. The present review offers the latest updates in management of this important clinical entity and a guidance framework for future research. HOW TO CITE THIS ARTICLE: Lahiry S, Thakur S, Chakraborty DS. Advances in Vasodilatory Shock: A Concise Review. Indian J Crit Care Med 2019;23(10):475-480.

Effect of 1,25 dihydroxy vitamin D3 supplementation on pain relief in early rheumatoid arthritis.

BACKGROUND: To assess effect of 1,25 dihydroxy vitamin D3 supplementation on pain relief in early rheumatoid arthritis (RA). MATERIALS AND METHODS: An open-labeled randomized trial was conducted comparing 60,000 IU 1,25 dihydroxy vitamin D3 + calcium (1000 mg/day) combination [Group A] versus calcium (1000 mg/day) only [Group B], as supplement to existing treatment regimen in early RA. Primary outcome included (i) minimum time required for onset of pain relief (Tm) assessed through patients' visual analog scale (VAS); (ii) % change in VAS score from onset of pain relief to end of 8 weeks. Secondary outcome included change in disease activity score (DAS-28). RESULTS: At the end of 8-weeks, Group A reported 50% higher median pain relief scores (80% vs. 30%; P < 0.001) and DAS-28 scores (2.9 ± 0.6 vs. 3.1 ± 0.4; P = 0.012) compared to Group B; however, Tm remained comparable (19 ± 2 vs. 20 ± 2 days; P = 0.419). Occurrence of hypovitaminosis-D was lower (23.3%) compared to Indian prevalence rates and was a risk factor for developing active disease (Odds Ratio (OR) = 7.52 [95% Confidence Interval (CI) 2.67-21.16], P < 0.0001). Vitamin D deficiency was significantly (P < 0.001) more common in female gender, active disease, and shorter mean disease duration. Vitamin D levels were inversely correlated to disease activity as assessed by DAS-28 (r = -0.604; P < 0.001). CONCLUSIONS: Vitamin-D deficiency is a risk factor for developing active disease in RA. Weekly supplementation of 60,000 IU of 1,25 dihydroxy vitamin D3 in early RA results in greater pain relief. The number needed to treat for this additional pain relief was 2. IDENTIFIER: CTRI/2018/01/011532 (www.ctri.nic.in).