Considerations on pivotal clinical trial design of innovative new drugs for hematological malignancies / 白血病·淋巴瘤

The rapid changes in the research and development environment of new anti-tumor drugs in China have brought various challenges to drug innovation. How to explore the clinical advantages of new drugs in the early phase, and design scientific, reasonable and efficient pivotal clinical trials for drug registration accordingly, is one of the key challenges. This article takes innovative new drugs for hematological malignancies as an example, comprehensively elaborates the considerations on the timing for entering the pivotal clinical trial and the key elements of the trial design from the perspective of clinical reviewers.

Considerations on Clinical Development and Regulatory of the Oversea License-in Anti-tumor Drugs / 中国肺癌杂志

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Current Development Status and Consideration for Rare Hemorrhagic Disease Drugs / 罕见病研究

Hemophilia is the only rare hereditary hemorrhagic disorder included in the First Rare Diseases catalogue. However, rare bleeding diseases identified in the clinic are far more common than hemophilia. Most other rare hemorrhagic disorders have less effective treatment than hemophilia. Hemophilia has a history of successful drug development in rare hemorrhagic diseases, and the cycle between clinical research and drug development has been gradually realized. Drug research and pharmaceutical companies can refer to the drug research and development process in the field of hemophilia, learn from the experience of hemophilia drug research and develop treatments. The industry can increase drug development by strengthening basic research, focusing on the value of natural history research, the application of quantitative pharmacological tools and improving the efficiency of drug development to meet the urgent unmet medical needs of patients with rare hemorrhagic diseases.

Effects of Shoe Type and Walking Speed on Knee Joint Loads / 医用生物力学

Objective To investigate the effects of shoes type (barefoot, ordinary running shoes, minimalist shoes) and walking speed (jogging, walking at normal speed) on biomechanical parameters of knee joint, so as to provide theoretical reference for scientific fitness. Methods Vicon three-dimensional （3D） motion capture system and Kistler 3D force plate were used to collect biomechanical parameters of lower limbs from 10 subjects during walking at different speed with different shoes. Two-way (2 walking conditions × 3 shoe conditions) repeated measures analysis of variance was used to statistically analyze each dependent variable. Results Compared with jogging, the lateral excursion of plantar center of pressure (COP) was greater, the moment arm in frontal plane, the adduction moment and peak loading rate of knee joint were smaller, but the angular impulse of knee joint in frontal plane was greater. Compared with ordinary running shoes, the stride length was decreased, the lateral excursion of COP was greater, and the moment arm of knee joint in frontal plane, the knee adduction moment, the peak load rate and the angular impulse of knee joint in frontal plane were smaller. Conclusions In order to reduce the angular impulse and peak loading rate of knee joint in frontal plane, it is recommended to jog with small strides for ordinary people with minimalist footwear.

Effect of chin-down-plus-larynx-tightening maneuver on improving choking cough and swallowing function in patients after esophageal cancer surgery / 中国实用护理杂志

Objective:To explore the effect of Chin-down-plus-larynx-tightening maneuver on improving choking cough and swallowing function in patients after esophageal cancer surgery.Methods:A total of 121 patients with esophageal cancer surgery had been randomly divided into control group and observation group from November 2018 to September 2019. Starting from feeding after surgery, the head and neck were in normal habits when swallowing in the control group, and the observation group used Chin-down-plus-larynx-tightening maneuver to perform swallowing training. The feeding process of two groups was observed and recorded for one week. One week after eating, the water swallowing test and M. D. Anderson Symptom Inventory for Gastrointestinal cancer (MDASI-GI) were used to evaluate the difference of swallowing function and gastrointestinal symptoms between the two groups.Results:During one week period of feeding, the incidence of choking cough in observation group was 3.39%, (2/59), which was significantly lower than that in the control group (14.52%, 9/62)( χ2 value was 4.53, P=0.033). After one week of feeding, the swallowing function showed significant difference ( Z value was 6.07, P=0.014), the gastrointestinal symptoms and the degree of life interference caused by gastrointestinal symptoms of observation group scored 2.57 ± 0.81, 1.76 ± 0.84, lower than those of the control group (4.25 ± 1.54, 2.18 ± 1.24), and the difference was statistically significant( t values were -7.56, -2.17, P<0.05). Conclusions:The Chin-down-plus-larynx-tightening maneuver can promote recovery of postoperative swallowing function in patients with esophageal cancer, reduce the incidence of choking cough, and help reduce the symptoms of digestive tract, and then raise the level of patient′s clinical prognosis.

Identification of the related substances in bendamustine hydrochloride / 中国药科大学学报

@#In the HPLC analysis of bendamustine hydrochloride, two related substances(IMP01 and IMP02)were detected. These two related substances were identified by LC-MS/MS and their structural confirmation was unambiguously carried out by synthesis followed by characterization using Q-TOF/MS and NMR. Based on the spectral data, related substances IMP01 and IMP02 were characterized as 4-(1-methyl-5-morpholino-1H-benzo［d］imidazol-2-yl)butyric acid hydrochloride and 4-{1-methyl-5-［(2-chloroethyl)(2-hydroxyethyl)amino］-1H-benzo［d］imidazol-2-yl)} butyric acid hydrochloride, respectively. Bendamustine hydrochloride and its related substances were separated under the established LC-MS condition. HPLC is a useful method for the determination of the related substances in bendamustine hydrochloride. Results obtained are valuable for its manufacturing process and quality control.