Prospective Comparisons of Clinical Trial and Real-world Outcomes in Nasopharyngeal Carcinoma
Condition: Nasopharyngeal Carcinoma
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma
Study type: Observational [Patient Registry]

Summary: 
      Study results from randomized controlled trials (RCTs) usually have been found not adequately
      inform practice. A RCT is optimized to determine efficacy, while real-world study is
      conducted in a routine care setting aimed to determine effectiveness. Thus, it is necessary
      to evaluate the pragmatism of clinical trials for a better understanding of the external
      generalizability. Nonetheless, comparative pragmatic features of RCTs and real-world studies
      still lack well elucidation. By capitalizing on a nasopharyngeal carcinoma (NPC)-specific
      big-data, real-world database and individual patient data extracted from three landmark RCTs,
      investigators conducted the direct comparison of NPC cohorts receiving same treatment
      strategy in clinical trial versus real-world settings, and examined the comparative pragmatic
      features and their influences on survival outcomes, safety profile, and the probability of
      returning to society.
    

Detailed description: 
      Study results from randomized controlled trials (RCTs) usually have been found not adequately
      inform practice. A RCT is optimized to determine efficacy. Such trials were performed with
      relatively small samples at sites with experienced investigators and highly selected
      participants, they could be overestimating benefits and underestimating harm. Real-world
      study is conducted in a routine care setting aimed to determine effectiveness. Thus, it is
      necessary to evaluate the pragmatism of clinical trials for a better understanding of the
      external generalizability. Nonetheless, comparative pragmatic features of RCTs and real-world
      studies still lack well elucidation. Nasopharyngeal carcinoma (NPC) is a malignant head and
      neck cancer with the highest incidences in endemic regions such as Southern China, where over
      60,600 new cases were diagnosed in 2015 representing 40% of all cases worldwide. Studies
      conducted in China are critical in optimizing clinical decision-making of NPC. In the past
      two decades, the recommendation level of induction chemotherapy (IC) + concurrent
      chemoradiotherapy (CCRT) has been improved evidently from Category 3 to 2A, and CCRT alone
      has long been a stable (Category 2B) and classic treatment option of NPC and therefore
      becomes the most commonly used control group in comparative studies. By capitalizing on a
      NPC-specific big-data, real-world database via a cancer registry in Southern China and
      individual patient data extracted from the three landmark RCTs, investigators conducted the
      direct comparison on IC+CCRT cohort or CCRT cohort of clinical trial versus real-world
      settings, and examined the comparative pragmatic features and their influences on survival
      outcomes, safety profile, and the probability of returning to society, with the aim to
      provide new insight into the optimization of trial design and the translation of study
      evidences into tangible benefits.
    

Intervention name(s): Trial setting
Intervention type(s): Other
Intervention description(s): Study results from clinical trials usually have been found not work efficiently in clinical practice. This outcome disparity may be caused by different pragmatic features of medical environment, also known as study setting such as trial setting and real-world setting, in which biases inherent to clinical trial design restrict its applicability even though all confounding factors are avoided.
Other intervention name(s): Explanatory medical environment; Non-pragmatic features
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with locoregionally advanced nasopharyngeal carcinoma (T3-4N1 and T1-4N2-3). There
        are two parts of the constitution of study population.

        Part 1. 1,468 subjects from three phase 3 randomized controlled trials ((NCT00677118,
        NCT01245959, and NCT01872962) that were conducted by our research team and had been
        published.

        Part 2. 3,980 subjects from the NPC-specific big-data, real-world database via a cancer
        registry in Southern China.
      
Keywords: Clinical trial; Real-world study; Nasopharyngeal carcinoma; Pragmatism; Survival; Return to society