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An evidence map of randomised controlled trials evaluating genetic therapies
  1. Eric A. Apaydin1,2,
  2. Andrea S. Richardson3,
  3. Sangita Baxi1,
  4. Jerry Vockley4,
  5. Olamigoke Akinniranye1,
  6. Rachel Ross5,
  7. Jody Larkin1,
  8. Aneesa Motala1,
  9. Gulrez Azhar1,
  10. Susanne Hempel1,6
  1. 1Southern California Evidence‐based Practice Center, Health Care, RAND Corporation, Santa Monica, California, USA
  2. 2Center for the Study of Healthcare Innovation, Implementation and Policy, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
  3. 3Southern California Evidence‐based Practice Center, Health Care, RAND Corporation, Pittsburgh, Pennsylvania, USA
  4. 4Division of Medical Genetics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  5. 5West Los Angeles Medical Center, Kaiser Foundation Hospitals, Los Angeles, California, USA
  6. 6Southern California Evidence Review Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  1. Correspondence to Dr. Eric A. Apaydin, Southern California Evidence-based Practice Center, Health Care, RAND Corporation, Santa Monica, CA 90401-3208, USA; eapaydin{at}


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

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  • Presented at This review was presented as a poster at the Society for General Internal Medicine 2020 On-Demand online meeting.

  • Contributors EAA serves as the guarantor for this manuscript. SH, ASR and EAA conceived the review. EAA drafted the manuscript and approved the final version. SB created the evidence map figures. JV provided content expertise. JL conducted the searches. AM managed the reference database and created the PRISMA flow diagram. SH, EAA, ASR, OA, RR and GA screened records for inclusion and abstracted included articles. All authors contributed to the manuscript and approved the final version.

  • Funding Research reported in this manuscript was funded through a contract with the Patient-Centered Outcomes Research Institute (PCORI; TORFP # PCO-Genetic Therapy-Task Order # 8). EAA was supported by the VA Office of Academic Affiliations through the Advanced Fellowship in Health Servcies Research & Development.

  • Disclaimer The contents of this work are solely the responsibility of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors or Methodology Committee, or the US Department of Veterans Affairs.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was reviewed by the RAND Human Subjects Protection Committee and declared to be exempt (2018–0560).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • 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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