OBJECTIVE To explore the key technical considerations in the drugs design of clinical trials for delaying the progression of chronic kidney disease. METHODS By reviewing domestic and foreign literature, and considering the characteristics of the disease, drug development and review experience, the important design considerations for clinical trials evaluating drugs that delay the progression of chronic kidney disease were suggested in this article. RESULTS and CONCLUSION We recommend an overall trial design that incorporates randomization, double-blinding, and placebo/standard treatment as control measures. The study population should be representative of a wide range of individuals who reflect the intended objectives of the trial. Inclusion criteria and efficacy evaluation should take into account etiology, staging, risk factors for disease progression, and combined treatments. We suggest the composite endpoints based on clinical events as primary efficacy endpoints,while the average change rate in glomerular filtration rate is recommended for early or slowly progressing chronic kidney disease cases. Safety evaluation indicators should not only adhere to general standards but also consider potential safety issues related to investigational drugs as well as safety signals associated with natural disease progression by setting corresponding safety assessment parameters for underlying diseases.

OBJECTIVE To discuss the characteristics of research and development on the new drugs of renal disease and technical considerations envolved. METHODS By investigating the advance of the regulatory agencies home and abroad and the related literature,the nephrotic drugs of the last decade in the market and in research were summerized domestically and overseas,the characteristics of research and key technical points were analyzed and relevant suggestions were put forward. RESULTS and CONCLUSIONS Ten new drugs have been approved by China,European Union and United States since 2013. The applications of the new drugs on this field has continued to increase in the recent 5 years, mainly on the chronic kidney disease and IgA nephropathy. To better promote the drug innovation development in this field, the following aspects should be paid attention to: The first is to further strengthen the basic scientific research about the pathogenesis of diseases, and screen the potential new drugs with new target and mechanism, so that make it possible to delay and even reverse the progression of the disease. The second is to better evaluate the patients beneifts by developing scientific and rational clinical outcome assessment tools with the basis of the patients' needs. The third is to choose the representative population by the combination of epidemiology, natural history, the feature of drugs and the aim of clinical trials since the pathology of renal diseases is complicated. The fourth, early management of renal disease is crucial. So it's of great significance to explore, develop and validate the surrogate endpoints since the disease progresses slowly and the investigation often requires both long study cycle of several years or even longer and a larger sample size. The surrogate indicators should be selected prudently. The sponsors are suggested to communicate with the regulatory agency when necessary. The fifth, a sufficent safety study can be very supportive to the general evaluation of benefit-risk balance.

OBJECTIVE To discuss technical considerations for the design of efficacy evaluation indicators for drugs used in the treatment of kidney disease. METHODS Based on practical experience in disease characteristics, drug development, and evaluation, technical recommendations were proposed for designing efficacy evaluation indicators for kidney disease treatment drugs. RESULTS and CONCLUSION Renal failure and cardiovascular death are considered as the primary clinical outcomes for evaluating the efficacy of drugs used in kidney disease treatment. Based of the urgent clinical need and slow progression of kidney disease, exploring the selection and application of intermediate/surrogate indicators holds significant clinical value. Some evidence suggests that improvement in estimated glomerular filtration rate (eGFR) slope can partially predict the clinical benefits of treatment on chronic kidney disease (CKD) progression, making it a potential alternative indicator for early or slowly progressing CKD patients in drug trials. The correlation between elevated urinary protein levels and duration with renal function loss in lupus nephritis, membranous nephropathy, and IgA nephropathy indicates their potential for predicting renal outcomes; however, further research evidence is still required. In conclusion, when selecting indicators to evaluate efficacy, scientific design should be based on trial objectives, target population characteristics, drug mechanisms of action, and effect intensity while carefully considering surrogate indicators.

OBJECTIVE To explore general technical considerations for the clinical trial design of drugs targeting lupus nephritis treatment. METHODS By conducting comprehensive research on relevant technical standards both domestically and internationally, synthesizing the experience gained from recent drug development endeavors, and integrating disease characteristics, treatment requirements, and evaluation practices, the holistic design of clinical trials for lupus nephritis drugs were explored from a technical evaluation perspective which including examining participant selection criteria, efficacy indicators, safety evaluations, and proposing key technical considerations. RESULTS and CONCLUSION The recommended research design is a multicenter, randomized, double-blind, parallel-controlled design typically conducted using standard treatment protocols. Including participants who have undergone renal biopsy within 6 months prior to randomization can enhance the representation of baseline characteristics. In terms of efficacy evaluation indicators, relying solely on a single indicator is insufficient to fully capture the effectiveness of the drug; therefore, composite indicators are commonly employed for comprehensive assessment purposes. The primary efficacy evaluation indicator should be the complete renal remission rate, with criteria that accurately reflect clinically significant improvement in kidney function. Secondary efficacy indicators should encompass multiple dimensions aligned with clinical treatment goals for lupus nephritis and include assessments of glucocorticoid and/or immunosuppressant dosage reductions, long-term renal outcomes (such as progression to end-stage kidney disease), as well as evaluations of SLE manifestations and overall activity levels. Safety aspects necessitate vigilant monitoring for risks such as infection, cardiovascular events, malignant tumors, and potential impacts on renal function posed by novel drugs.