Hanna Eve, Rémuzat Cecile, Auquier Pascal, Toumi Mondher
Faculty of Medicine - Public Health department, University Aix-Marseille, Marseille, France.
Creativ-Ceutical, Paris, France.
J Mark Access Health Policy. 2016 Aug 2;4. doi: 10.3402/jmahp.v4.32232. eCollection 2016.
Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation.
We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation.
Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven.
No failure risk rate per development phase is available for ATMPs. The discontinuation rate may prove helpful when assessing the expected net present value to support portfolio arbitration and may be considered by patients and potential investigators in their decisions to participate in ATMP trials. These results carry limitation because the rationale for discontinuation is unknown. Further research about the reasons of discontinuation and the risk of negative results is needed to inform stakeholders.
先进治疗医药产品（ATMPs）构成了一类创新产品，涵盖基因治疗、体细胞治疗和组织工程产品（TEP）。商业和非商业赞助商在该领域的投资不断增加，参与此类试验的ATMPs随机临床试验（RCT）数量及患者人数也在不断增长。RCT用于生成数据以证明新疗法的疗效，但RCT的终止会浪费稀缺资源。我们的目标是确定已终止的ATMPs试验的数量和特征，以评估终止率。
我们使用三个数据库搜索了1999年至2015年6月期间开展的ATMPs试验，这三个数据库分别是Clinicaltrials.gov、国际临床试验注册平台（ICTRP）和欧盟药品监管当局临床试验（EudraCT）。在消除重复项后，我们筛选出了ATMPs试验。我们确定了疾病领域以及赞助商是商业组织还是非商业组织。我们根据类型和试验状态对ATMPs进行分类，即正在进行、已完成、已终止、已停止和提前结束。然后，我们计算了终止率。
在1999年至2015年6月期间，共识别出143项已撤回、已终止或提前结束的ATMPs临床试验。在1999年至2013年6月期间，共识别出474项正在进行和已完成的临床试验。因此，ATMPs试验的终止率为23.18%，与处于研发阶段的非ATMPs药物的终止率相似。细胞治疗、基因治疗和TEP的终止概率分别为27.35%、16.28%和16.34%。终止率最高的是肿瘤学领域（43%），其次是心脏病学领域（19.2%）。商业和非商业赞助商的终止率几乎相同；因此，终止原因可能并非由财务因素驱动。
目前尚无ATMPs在每个研发阶段的失败风险率。在评估预期净现值以支持投资组合仲裁时，终止率可能会有所帮助，患者和潜在研究者在决定是否参与ATMP试验时也可予以考虑。这些结果存在局限性，因为终止的理由尚不清楚。需要进一步研究终止原因以及负面结果的风险，以便为利益相关者提供信息。
