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Precision medicine needs randomized clinical trials

Nature Reviews Clinical Oncology volume 14, pages 317–323 (2017)Cite this article

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Abstract

The advent of precision medicine has prompted profound changes in clinical cancer research, and the rising numbers of new therapeutic agents pose challenges in terms of the most appropriate trial designs and effects on the drug-approval process. In the past 5 years, some remarkably efficacious drugs have been approved based on evidence from uncontrolled phase I trials. We challenge the view that the expected benefits from new drugs are generally sufficient to forgo a randomized trial with patients assigned to a control arm (a regimen other than the experimental treatment). Relying on efficacy results from uncontrolled clinical trials can result in expedited drug approval, but the disadvantages of this practice must be taken into account. For example, the apparent improvements in outcomes observed in an early single-arm trial of a new therapy might reflect the prognostic nature of the target, rather than a true treatment effect. Moreover, the predictive role of biomarkers cannot be definitively ascertained without randomly assigning patients to a control arm. We discuss the need for such randomization to a true control in all phases of drug development and the role of companion biomarker testing. We propose that an increased use of randomization will facilitate a seamless transition between phases of drug and/or biomarker development.

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Figure 1: Patient randomization in the continuum of drug and/or biomarker development.

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References

  1. Masters, G. A. et al. Clinical cancer advances 2015: Annual report on progress against cancer from the American Society of Clinical Oncology. J. Clin. Oncol. 33, 786–809 (2015).

    Article  PubMed  Google Scholar 

  2. US Food & Drug Administration Center for Drug Evaluation & Research. Novel New Drugs 2014 — Summary — January 2015. FDA http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM430299.pdf (2014).

  3. Malik, S. M. et al. U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive. Clin. Cancer Res. 20, 2029–2034 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Khozin, S. et al. FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. Clin. Cancer Res. 21, 2436–2439 (2015).

    Article  CAS  PubMed  Google Scholar 

  5. Ratain, M. J. & Sargent, D. J. Optimising the design of phase II oncology trials: the importance of randomisation. Eur. J. Cancer 45, 275–280 (2009).

    Article  PubMed  Google Scholar 

  6. Hennekens, C. H. & Demets, D. The need for large-scale randomized evidence without undue emphasis on small trials, meta-analyses, or subgroup analyses. JAMA 302, 2361–2362 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Hyman, D. M. et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N. Engl. J. Med. 373, 726–736 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lopez-Chavez, A. et al. Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial. J. Clin. Oncol. 33, 1000–1007 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kim, E. S. et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov. 1, 44–53 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mazieres, J. et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort. J. Clin. Oncol. 33, 992–999 (2015).

    Article  CAS  PubMed  Google Scholar 

  11. Kris, M. G. et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA 311, 1998–2006 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. American Society of Clinical Oncology. Targeted Agent and Profiling Utilization Registry (TAPUR). TAPUR http://www.tapur.org/ (2016).

  13. Grove, A. Rethinking clinical trials. Science 333, 1679 (2011).

    Article  CAS  PubMed  Google Scholar 

  14. Avorn, J. & Kesselheim, A. S. The 21st Century Cures Act — will it take us back in time? N. Engl. J. Med. 372, 2473–2475 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Buyse, M., Sargent, D. J., Grothey, A., Matheson, A. & de Gramont, A. Biomarkers and surrogate end points — the challenge of statistical validation. Nat. Rev. Clin. Oncol. 7, 309–317 (2010).

    Article  PubMed  Google Scholar 

  16. Dahlberg, S. E., Shapiro, G. I., Clark, J. W. & Johnson, B. E. Evaluation of statistical designs in phase I expansion cohorts: the Dana-Farber/Harvard Cancer Center experience. J. Natl Cancer Inst. 106, dju163 (2014).

    Article  PubMed  Google Scholar 

  17. Manji, A. et al. Evolution of clinical trial design in early drug development: systematic review of expansion cohort use in single-agent phase I cancer trials. J. Clin. Oncol. 31, 4260–4267 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Rogatko, A. et al. Translation of innovative designs into phase I trials. J. Clin. Oncol. 25, 4982–4986 (2007).

    Article  PubMed  Google Scholar 

  19. Le Tourneau, C., Lee, J. J. & Siu, L. L. Dose escalation methods in phase I cancer clinical trials. J. Natl Cancer Inst. 101, 708–720 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Riviere, M. K., Le Tourneau, C., Paoletti, X., Dubois, F. & Zohar, S. Designs of drug-combination phase I trials in oncology: a systematic review of the literature. Ann. Oncol. 26, 669–674 (2015).

    Article  PubMed  Google Scholar 

  21. Paoletti, X., Ezzalfani, M. & Le Tourneau, C. Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials. Ann. Oncol. 26, 1808–1812 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Weber, J. S. et al. American Society of Clinical Oncology policy statement update: the critical role of phase I trials in cancer research and treatment. J. Clin. Oncol. 33, 278–284 (2015).

    Article  PubMed  Google Scholar 

  23. Lee, J. J. & Feng, L. Randomized phase II designs in cancer clinical trials: current status and future directions. J. Clin. Oncol. 23, 4450–4457 (2005).

    Article  PubMed  Google Scholar 

  24. Sleijfer, S., Bogaerts, J. & Siu, L. L. Designing transformative clinical trials in the cancer genome era. J. Clin. Oncol. 31, 1834–1841 (2013).

    Article  PubMed  Google Scholar 

  25. Sharma, M. R., Stadler, W. M. & Ratain, M. J. Randomized phase II trials: a long-term investment with promising returns. J. Natl Cancer Inst. 103, 1093–1100 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mandrekar, S. J. & Sargent, D. J. Clinical trial designs for predictive biomarker validation: theoretical considerations and practical challenges. J. Clin. Oncol. 27, 4027–4034 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Buyse, M. & Michiels, S. Omics-based clinical trial designs. Curr. Opin. Oncol. 25, 289–295 (2013).

    Article  PubMed  Google Scholar 

  28. McLaughlin, P. et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J. Clin. Oncol. 16, 2825–2833 (1998).

    Article  CAS  PubMed  Google Scholar 

  29. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031–1037 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Mok, T. S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361, 947–957 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. Herbst, R. S. et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial — INTACT 2. J. Clin. Oncol. 22, 785–794 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Williams, R. Discontinued in 2013: oncology drugs. Expert Opin. Investig. Drugs 24, 95–110 (2015).

    Article  CAS  PubMed  Google Scholar 

  33. Tsimberidou, A. M. et al. Personalized medicine for patients with advanced cancer in the phase I program at MD Anderson: validation and landmark analyses. Clin. Cancer Res. 20, 4827–4836 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Schwaederle, M. et al. Impact of precision medicine in diverse cancers: a meta-analysis of phase II clinical trials. J. Clin. Oncol. 33, 3817–3825 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fontes Jardim, D. L. et al. Impact of a biomarker-based strategy on oncology drug development: a meta-analysis of clinical trials leading to FDA approval. J. Natl Cancer Inst. 107, djv253 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Schwaederle, M. et al. Association of biomarker-based treatment strategies with response rates and progression-free survival in refractory malignant neoplasms: a meta-analysis. JAMA Oncol. 2, 1452–1459 (2016).

    Article  PubMed  Google Scholar 

  37. Dienstmann, R. et al. Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials. Mol. Cancer Ther. 11, 2062–2071 (2012).

    Article  CAS  PubMed  Google Scholar 

  38. Le Tourneau, C. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 16, 1324–1334 (2015).

    Article  CAS  PubMed  Google Scholar 

  39. Catenacci, D. V. Expansion platform type II: testing a treatment strategy. Lancet Oncol. 16, 1276–1278 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Le Tourneau, C. & Kurzrock, R. Targeted therapies: what have we learned from SHIVA? Nat. Rev. Clin. Oncol. 13, 719–720 (2016).

    Article  CAS  PubMed  Google Scholar 

  41. Gerlinger, M. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883–892 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Liu, X. et al. Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor. Clin. Cancer Res. 18, 510–523 (2012).

    Article  CAS  PubMed  Google Scholar 

  43. Eberhard, D. A. et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J. Clin. Oncol. 23, 5900–5909 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Schmoor, C. & Schumacher, M. Methodological arguments for the necessity of randomized trials in high-dose chemotherapy for breast cancer. Breast Cancer Res. Treat. 54, 31–38 (1999).

    Article  CAS  PubMed  Google Scholar 

  45. Tannock, I. F. Some problems related to the design and analysis of clinical trials. Int. J. Radiat. Oncol. Biol. Phys. 22, 881–885 (1992).

    Article  CAS  PubMed  Google Scholar 

  46. Chabner, B. A. Early accelerated approval for highly targeted cancer drugs. N. Engl. J. Med. 364, 1087–1089 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. Kummar, S. et al. Application of molecular profiling in clinical trials for advanced metastatic cancers. J. Natl Cancer Inst. 107, djv003 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Kurzrock, R. & Stewart, D. J. Equipoise abandoned? Randomization and clinical trials. Ann. Oncol. 24, 2471–2474 (2013).

    Article  CAS  PubMed  Google Scholar 

  49. Djulbegovic, B., Hozo, I. & Ioannidis, J. P. Improving the drug development process: more not less randomized trials. JAMA 311, 355–356 (2014).

    Article  CAS  PubMed  Google Scholar 

  50. Gehan, E. A. & Freireich, E. J. Non-randomized controls in cancer clinical trials. N. Engl. J. Med. 290, 198–203 (1974).

    Article  CAS  PubMed  Google Scholar 

  51. Sanwald-Ducray, P., Liogier D'ardhuy, X., Jamois, C. & Banken, L. Pharmacokinetics, pharmacodynamics, and tolerability of aleglitazar in patients with type 2 diabetes: results from a randomized, placebo-controlled clinical study. Clin. Pharmacol. Ther. 88, 197–203 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Perlstein, I., Bolognese, J. A., Krishna, R. & Wagner, J. A. Evaluation of agile designs in first-in-human (FIH) trials — a simulation study. AAPS J. 11, 653–663 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mathijssen, R. H., Sparreboom, A. & Verweij, J. Determining the optimal dose in the development of anticancer agents. Nat. Rev. Clin. Oncol. 11, 272–281 (2014).

    Article  CAS  PubMed  Google Scholar 

  54. Postel-Vinay, S. et al. Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents — Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study. Eur. J. Cancer 50, 2040–2049 (2014).

    Article  PubMed  Google Scholar 

  55. Jain, R. K. et al. Phase I oncology studies: evidence that in the era of targeted therapies patients on lower doses do not fare worse. Clin. Cancer Res. 16, 1289–1297 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sachs, J. R., Mayawala, K., Gadamsetty, S., Kang, S. P. & de Alwis, D. P. Optimal dosing for targeted therapies in oncology: drug development cases leading by example. Clin. Cancer Res. 22, 1318–1324 (2016).

    Article  CAS  PubMed  Google Scholar 

  57. Agrawal, M. & Emanuel, E. J. Ethics of phase 1 oncology studies: reexamining the arguments and data. JAMA 290, 1075–1082 (2003).

    Article  PubMed  Google Scholar 

  58. Kodish, E., Stocking, C., Ratain, M. J., Kohrman, A. & Siegler, M. Ethical issues in phase I oncology research: a comparison of investigators and institutional review board chairpersons. J. Clin. Oncol. 10, 1810–1816 (1992).

    Article  CAS  PubMed  Google Scholar 

  59. Roberts, T. G. Jr et al. Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials. JAMA 292, 2130–2140 (2004).

    Article  CAS  PubMed  Google Scholar 

  60. Flaherty, K. T. et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809–819 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Janne, P. A. et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N. Engl. J. Med. 372, 1689–1699 (2015).

    Article  PubMed  Google Scholar 

  62. Cortes, J. E. et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N. Engl. J. Med. 367, 2075–2088 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Horstmann, E. et al. Risks and benefits of phase 1 oncology trials, 1991 through 2002. N. Engl. J. Med. 352, 895–904 (2005).

    Article  CAS  PubMed  Google Scholar 

  64. Estey, E. et al. Therapeutic response in phase I trials of antineoplastic agents. Cancer Treat. Rep. 70, 1105–1115 (1986).

    CAS  PubMed  Google Scholar 

  65. Robert, C. et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384, 1109–1117 (2014).

    Article  CAS  PubMed  Google Scholar 

  66. Theoret, M. R. et al. Expansion cohorts in first-in- human solid tumor oncology trials. Clin. Cancer Res. 21, 4545–4551 (2015).

    Article  PubMed  Google Scholar 

  67. Chalmers, T. C. Randomization of the first patient. Med. Clin. North Am. 59, 1035–1038 (1975).

    Article  CAS  PubMed  Google Scholar 

  68. Johnson, J. R., Williams, G. & Pazdur, R. End points and United States Food and Drug Administration approval of oncology drugs. J. Clin. Oncol. 21, 1404–1411 (2003).

    Article  PubMed  Google Scholar 

  69. Simon, R., Wittes, R. E. & Ellenberg, S. S. Randomized phase II clinical trials. Cancer Treat. Rep. 69, 1375–1381 (1985).

    CAS  PubMed  Google Scholar 

  70. Saad, E. D. et al. Formal statistical testing and inference in randomized phase II trials in medical oncology. Am. J. Clin. Oncol. 36, 143–145 (2013).

    Article  PubMed  Google Scholar 

  71. Tang, H. et al. Comparison of error rates in single-arm versus randomized phase II cancer clinical trials. J. Clin. Oncol. 28, 1936–1941 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Jardim, D. L., Groves, E. S., Breitfeld, P. P. & Kurzrock, R. Factors associated with failure of oncology drugs in late-stage clinical development: a systematic review. Cancer Treat. Rev. 52, 12–21 (2016).

    Article  PubMed  Google Scholar 

  73. Hey, S. P. & Kimmelman, J. Are outcome-adaptive allocation trials ethical? Clin. Trials 12, 102–106 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Buyse, M. Commentary on Hey and Kimmelman. Clin. Trials 12, 119–121 (2015).

    Article  PubMed  Google Scholar 

  75. Harrington, D. & Parmigiani, G. I-SPY 2 — a glimpse of the future of phase 2 drug development? N. Engl. J. Med. 375, 7–9 (2016).

    Article  PubMed  Google Scholar 

  76. Park, J. W. et al. Adaptive randomization of neratinib in early breast cancer. N. Engl. J. Med. 375, 11–22 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Korn, E. L. & Freidlin, B. Outcome — adaptive randomization: is it useful? J. Clin. Oncol. 29, 771–776 (2011).

    Article  PubMed  Google Scholar 

  78. Saxman, S. B. Ethical considerations for outcome-adaptive trial designs: a clinical researcher's perspective. Bioethics 29, 59–65 (2015).

    Article  PubMed  Google Scholar 

  79. Simon, R. et al. The role of nonrandomized trials in the evaluation of oncology drugs. Clin. Pharmacol. Ther. 97, 502–507 (2015).

    Article  CAS  PubMed  Google Scholar 

  80. Boyd, N., Dancey, J. E., Gilks, C. B. & Huntsman, D. G. Rare cancers: a sea of opportunity. Lancet Oncol. 17, e52–e61 (2016).

    Article  PubMed  Google Scholar 

  81. Bayar, M. A., Le Teuff, G., Michiels, S., Sargent, D. J. & Le Deley, M. C. New insights into the evaluation of randomized controlled trials for rare diseases over a long-term research horizon: a simulation study. Stat. Med. 35, 3245–3258 (2016).

    Article  PubMed  Google Scholar 

  82. Gan, H. K. et al. Randomized phase II trials: inevitable or inadvisable? J. Clin. Oncol. 28, 2641–2647 (2010).

    Article  PubMed  Google Scholar 

  83. Ellis, M. J. et al. Fulvestrant 500 mg versus anastrozole 1 mg for the first-line treatment of advanced breast cancer: overall survival analysis from the phase II FIRST Study. J. Clin. Oncol. 33, 3781–3787 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Sehn, L. H. et al. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS Study. J. Clin. Oncol. 33, 3467–3474 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Rosell, R. et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13, 239–246 (2012).

    Article  CAS  PubMed  Google Scholar 

  86. Zhou, C. et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 12, 735–742 (2011).

    Article  CAS  PubMed  Google Scholar 

  87. Buyse, M. Limitations of adaptive clinical trials. Am. Soc. Clin. Oncol. Educ. Book 2012, 133–137 (2012).

    Article  Google Scholar 

  88. Fischl, M. A. et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N. Engl. J. Med. 317, 185–191 (1987).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the three reviewers who anonymously contributed to our paper with their insightful and constructive critique.

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Authors and Affiliations

  1. Everardo D. Saad is at the International Drug Development Institute (IDDI), Avenue Provinciale 30, 1340 Ottignies-Louvain-la-Neuve, Belgium.,

    Everardo D. Saad

  2. Xavier Paoletti is at the Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France.,

    Xavier Paoletti

  3. Tomasz Burzykowski is at the IDDI, Avenue Provinciale 30, 1340 Ottignies-Louvain-la-Neuve, Belgium,

    Tomasz Burzykowski

  4. at the Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BioStat), Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium.,

    Tomasz Burzykowski

  5. Marc Buyse is at the I-BioStat, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium,

    Marc Buyse

  6. at the IDDI, 185 Alewife Brook Parkway, Suite 410, Cambridge, Massachusetts 02138, USA.,

    Marc Buyse

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  1. Everardo D. Saad
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  2. Xavier Paoletti
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All authors researched data for the article and contributed to discussions of the article's content. E.D.S. and M.B. wrote, reviewed, and edited the manuscript before submission.

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Correspondence to Everardo D. Saad.

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Saad, E., Paoletti, X., Burzykowski, T. et al. Precision medicine needs randomized clinical trials. Nat Rev Clin Oncol 14, 317–323 (2017). https://doi.org/10.1038/nrclinonc.2017.8

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