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An evidence map of randomised controlled trials evaluating genetic therapies


Objectives 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.

Eligibility criteria 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.

Information sources We searched PubMed, EMBASE, Web of Science, and grey literature to November 2018.

Risk of bias Only RCTs were included in this review to reduce the risk of selection bias in the evaluation of genetic therapy safety and efficacy.

Included studies We identified 119 RCTs evaluating genetic therapies for a variety of clinical conditions.

Synthesis of results 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.

Description of the effect 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.

Strengths and limitations of evidence 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.

Interpretation 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.

  • genetics
  • therapeutics
  • evidence map

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. All included articles are detailed in online supplemental material table S1.

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