Apaydin Eric A, Richardson Andrea S, Baxi Sangita, Vockley Jerry, Akinniranye Olamigoke, Ross Rachel, Larkin Jody, Motala Aneesa, Azhar Gulrez, Hempel Susanne
Southern California Evidence-based Practice Center, Health Care, RAND Corporation, Santa Monica, California, USA
Center for the Study of Healthcare Innovation, Implementation and Policy, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.
BMJ Evid Based Med. 2020 Nov 10. doi: 10.1136/bmjebm-2020-111448.
Genetic therapies replace or inactivate disease-causing genes or introduce new or modified genes. These therapies have the potential to cure in a single application rather than treating symptoms through repeated administrations. This evidence map provides a broad overview of the genetic therapies that have been evaluated in randomised controlled trials (RCTs) for efficacy and safety.
Two independent reviewers screened publications using predetermined eligibility criteria. Study details and data on safety and efficacy were abstracted from included trials. Results were visualised in an evidence map.
We searched PubMed, EMBASE, Web of Science, ClinicalTrials.gov and grey literature to November 2018.
Only RCTs were included in this review to reduce the risk of selection bias in the evaluation of genetic therapy safety and efficacy.
We identified 119 RCTs evaluating genetic therapies for a variety of clinical conditions.
On average, samples included 107 participants (range: 1-1022), and were followed for 15 months (range: 0-124). Interventions using adenoviruses (40%) to treat cardiovascular diseases (29%) were the most common.
In RCTs reporting safety and efficacy outcomes, in the majority (60%) genetic therapies were associated with improved symptoms but in nearly half (45%) serious adverse event (SAEs) were also reported. Improvement was reported in trials treating cancer, cardiovascular, ocular and muscular diseases. However, only 19 trials reported symptom improvement for at least 1 year.
This is the first comprehensive evidence map of RCTs evaluating the safety and efficacy of genetic therapies. Evidence for long-term effectiveness and safety is still sparse. This lack of evidence has implications for the use, ethics, pricing and logistics of genetic therapies.
This evidence map provides a broad overview of research studies that allow strong evidence statements regarding the safety and efficacy of genetic therapies. Most interventions improve symptoms, but SAE are also common. More research is needed to evaluate genetic therapies with regard to the potential to cure diseases.
基因疗法可替换或使致病基因失活，或引入新的或经过修饰的基因。这些疗法有可能单次应用即治愈疾病，而非通过反复给药来治疗症状。本证据图谱对已在随机对照试验（RCT）中评估疗效和安全性的基因疗法进行了全面概述。
两名独立评审员使用预先确定的纳入标准筛选出版物。从纳入的试验中提取研究细节以及关于安全性和疗效的数据。结果在证据图谱中可视化呈现。
我们检索了截至2018年11月的PubMed、EMBASE、科学网、临床试验.gov以及灰色文献。
本综述仅纳入随机对照试验，以降低在评估基因疗法安全性和疗效时选择偏倚的风险。
我们确定了119项评估针对各种临床病症的基因疗法的随机对照试验。
平均而言，样本包含107名参与者（范围：1 - 1022），随访时间为15个月（范围：0 - 124）。使用腺病毒（40%）治疗心血管疾病（29%）的干预最为常见。
在报告安全性和疗效结果的随机对照试验中，大多数（60%）基因疗法与症状改善相关，但近一半（45%）也报告了严重不良事件（SAE）。在治疗癌症、心血管疾病、眼部疾病和肌肉疾病的试验中均报告有改善。然而，只有19项试验报告症状改善至少持续1年。
这是首个评估基因疗法安全性和疗效的随机对照试验的综合证据图谱。关于长期有效性和安全性的证据仍然稀少。这种证据的缺乏对基因疗法 的使用、伦理、定价和物流产生影响。
本证据图谱对研究进行了全面概述，这些研究使得能够就基因疗法的安全性和疗效做出有力的证据陈述。大多数干预措施可改善症状，但严重不良事件也很常见。需要更多研究来评估基因疗法治愈疾病的潜力。
