Request for comments on the statistical guidelines for clinical research of rare disease drugs

Recently, the Center for Drug Evaluation of the State Food and Drug Administration publicly solicited opinions on the "Guiding Principles for Clinical Research of Rare Disease Drugs (Draft for Comment)" (hereinafter referred to as the Draft for Comment)
.
The draft involves the design and analysis of clinical research on rare disease drugs, precautions in the implementation of clinical research, and evaluation of evidence.
It focuses on ensuring the quality of the research and the reliability of the results and improving the efficiency of research and development, and elaborates on key statistical issues
.
Related content proposes that due to the small overall patient population, clinical research on rare disease drugs may consider appropriately relaxing the entry and exclusion criteria to allow a relatively large number of patients to enter the study
.
For rare diseases that affect both adults and children, sponsors should consider including pediatric patients in clinical studies as soon as possible
.

 

For the clinical research design and analysis of rare disease drugs, the draft for comments introduces the general considerations of the clinical research design stage, including the natural history of the disease, entry and exclusion criteria , research endpoints, randomization, blinding, type I error control and other key statistics for clinical research Scientific elements; several research design methods that may be applicable to rare diseases , including methods of adding other design elements to routine randomized controlled trials (such as sequential design, response adaptive design, etc.
), single-arm trials, and real-world studies ; Introduced the relevant content of sample size estimation and the content to be considered in statistical analysis methods, and pointed out that in actual drug development, the sponsor should choose an appropriate design according to the trial purpose and specific circumstances.
If single-arm trials, real-world studies, etc.
are used as registration applications The sponsor should explain its rationality, communicate with the regulatory agency in advance and reach an agreement
.

 

　　Clinical research of rare disease drugs often faces problems such as difficulty in enrollment, long enrollment time, limited sample size, high heterogeneity of enrolled subjects, and lack of effective treatment methods, which require higher quality of clinical research
.
The draft for comments detailed the problems frequently encountered in clinical trials of rare diseases and the matters needing attention, including the selection of clinical research centers, patient compliance, research cycle, entry and discharge standards, data quality, and follow-up
.
In addition, according to the draft for comments, under the same regulatory standards as the evaluation of drugs for common diseases, the evaluation of evidence for rare disease drugs needs to be elaborated in terms of effectiveness and safety evidence evaluation and benefit and risk evaluation
.

　　Recently, the Center for Drug Evaluation of the State Food and Drug Administration publicly solicited opinions on the "Guiding Principles for Clinical Research of Rare Disease Drugs (Draft for Comment)" (hereinafter referred to as the Draft for Comment)
.
The draft involves the design and analysis of clinical research on rare disease drugs, precautions in the implementation of clinical research, and evaluation of evidence.
It focuses on ensuring the quality of the research and the reliability of the results and improving the efficiency of research and development, and elaborates on key statistical issues
.
Related content proposes that due to the small overall patient population, clinical research on rare disease drugs may consider appropriately relaxing the entry and exclusion criteria to allow a relatively large number of patients to enter the study
.
For rare diseases that affect both adults and children, sponsors should consider including pediatric patients in clinical studies as soon as possible
.

 

　　For the clinical research design and analysis of rare disease drugs, the draft for comments introduces the general considerations of the clinical research design stage, including the natural history of the disease, entry and exclusion criteria , research endpoints, randomization, blinding, type I error control and other key statistics for clinical research Scientific elements; several research design methods that may be applicable to rare diseases , including methods of adding other design elements to routine randomized controlled trials (such as sequential design, response adaptive design, etc.
), single-arm trials, and real-world studies ; Introduced the relevant content of sample size estimation and the content to be considered in statistical analysis methods, and pointed out that in actual drug development, the sponsor should choose an appropriate design according to the trial purpose and specific circumstances.
If single-arm trials, real-world studies, etc.
are used as registration applications The sponsor should explain its rationality, communicate with the regulatory agency in advance and reach an agreement
.

 

　　Clinical research of rare disease drugs often faces problems such as difficulty in enrollment, long enrollment time, limited sample size, high heterogeneity of enrolled subjects, and lack of effective treatment methods, which require higher quality of clinical research
.
The draft for comments detailed the problems frequently encountered in clinical trials of rare diseases and the matters needing attention, including the selection of clinical research centers, patient compliance, research cycle, entry and discharge standards, data quality, and follow-up
.
In addition, according to the draft for comments, under the same regulatory standards as the evaluation of drugs for common diseases, the evaluation of evidence for rare disease drugs needs to be elaborated in terms of effectiveness and safety evidence evaluation and benefit and risk evaluation
.