Authier Simon, Vargas Hugo M, Curtis Michael J, Holbrook Mark, Pugsley Michael K
CIToxLAB North America, 445 Armand Frappier, Laval, QCH7V 4B3 Canada.
J Pharmacol Toxicol Methods. 2013 Jul-Aug;68(1):44-51. doi: 10.1016/j.vascn.2013.05.002. Epub 2013 May 14.
The Safety Pharmacology (SP) Society (SPS) conducted an industry survey in 2012 in an attempt to define current industry practices as they relate to inclusion of safety pharmacology (SP) endpoints into Toxicology studies.
A total of 361 participants from Asia (9.1%), Europe (19.4%) and North America (71.4%) responded to the survey. The preponderance of respondents were toxicologists (53.2%) followed by safety pharmacologists (27.2%) and scientists involved in the conduct of both disciplines (19.6%). Most participants (58.6%) were from pharmaceutical companies employing more than 500 employees.
A majority (68.2%) reported having experience in designing, performing or interpreting the SP component of a study when performed as part of a toxicology study. Some participants (42.0%) had submitted data to a regulatory agency where ICHS7 studies were performed as part of a toxicology study rather than as a standalone study. When comparing species that were used in studies in which SP was added to toxicology studies, canines were the most frequently reported animals used for new chemical entities (NCE) whereas non-human (NH) primates were the most frequent for the assessment of biological agents. The most frequent primary motivator for adding ICHS7 SP endpoints to regulatory toxicology studies was to generate additional data to allow for determination of an integrated risk assessment thereby testing Confidence in Safety (CIS) to better manage and/or mitigate risk. The current ability to add safety pharmacology endpoints into regulatory toxicology studies was used to address a specific concern (by 42.1% of respondents) to allow management of risk more effectively (36.8%) or to generate data that contributes to cessation of the progression of a compound (21.1%). For an NCE, SP measurements in toxicology studies were conducted in addition to standalone SP studies (by 40.6% of respondents) or in addition/instead of standalone safety pharmacology studies (by 39.8% of respondents). For biological agents, a majority (74.3%) indicated SP measurements in toxicology were conducted instead of standalone studies as outlined in the ICHS6 guideline while inclusion of SP endpoints in toxicology studies for biological agents in addition to standalone studies was reported by only 25.7% of the respondents.
The survey highlights that obtaining regulatory agreement for the proposed combined SP/Tox study designs may be useful before study conduct in some cases. Respondents suggest that such discussion could occur at the pre-IND meeting before the IND/CTA enabling program.
安全药理学（SP）协会（SPS）于2012年开展了一项行业调查，旨在明确当前行业在将安全药理学（SP）终点纳入毒理学研究方面的做法。
共有来自亚洲（9.1%）、欧洲（19.4%）和北美（71.4%）的361名参与者回复了该调查。大多数受访者是毒理学家（53.2%），其次是安全药理学家（27.2%）以及从事这两个学科研究的科学家（19.6%）。大多数参与者（58.6%）来自员工超过500人的制药公司。
大多数（68.2%）报告称在将SP部分作为毒理学研究的一部分进行设计、实施或解读方面有经验。一些参与者（42.0%）已向监管机构提交数据，在这些数据中，ICHS7研究是作为毒理学研究的一部分而非独立研究进行的。在比较添加了SP的毒理学研究中所使用的物种时，犬类是新化学实体（NCE）研究中最常报告使用的动物，而非人（NH）灵长类则是生物制剂评估中最常使用的动物。在监管毒理学研究中添加ICHS7 SP终点的最常见主要动机是生成额外数据，以便进行综合风险评估，从而测试安全性信心（CIS）以更好地管理和/或降低风险。当前将安全药理学终点纳入监管毒理学研究的能力被用于解决特定问题（42.1%的受访者），以便更有效地管理风险（36.8%）或生成有助于停止化合物研发进程的数据（21.1%）。对于NCE，在毒理学研究中进行SP测量是在独立的SP研究之外（40.6%的受访者）或除了/代替独立的安全药理学研究（39.8%的受访者）。对于生物制剂，大多数（74.3%）表示毒理学中的SP测量是按照ICHS6指南进行的，而不是独立研究，只有25.7%的受访者报告在毒理学研究中除了独立研究之外还纳入了SP终点。
该调查强调，在某些情况下，在研究开展之前获得监管机构对拟议的联合SP/毒理学研究设计的认可可能是有用的。受访者建议这种讨论可以在IND/CTA启动计划之前的IND前会议上进行。
