Background
Methods
Results
Conclusion
Methods

Arguments in favor of acceptability of sham controls
The use of a sham control increases scientific validity
The use of a sham control increases benefits to future patients and society
The risks and harms of a sham control can be acceptable
- Sihvonen R.
- Paavola M.
- Malmivaara A.
- Jarvinen T.L.
Arguments against the acceptability of a sham control
A sham control often is unnecessary for scientific validity
A sham control does not increase benefits to society
- Sihvonen R.
- Paavola M.
- Malmivaara A.
- Jarvinen T.L.
Risks and harm to a sham control group are unacceptable
Difficulties in obtaining valid informed consent
Moral discomfort for investigator and participant
Active deception is not a priori unethical
Lack of support by public and researchers
Counter argument: sufficient support exists
Discussion
Arguments in favor | Arguments against |
---|---|
A sham intervention increases scientific validity | A sham intervention is often unnecessary for increasing scientific validity |
A sham intervention increases benefits to future patients and society | A sham intervention does not always increase benefits to society |
Risks and harm of a sham intervention can be acceptable | Risks and harm of a sham intervention are unacceptable |
Gaining valid informed consent is possible | Difficulties are present in obtaining a valid informed consent |
Active deception is not a priori unethical | Moral discomfort for investigator and participant can occur, mainly from active deception |
Sufficient support by public and researchers exists | There is a lack of trust and support by public and researchers |
World Medical Association. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. 2013. Available from: http://www.wma.net/en/30publications/10policies/b3/. Accessed Feb 5, 2015.
World Medical Association. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. 2013. Available from: http://www.wma.net/en/30publications/10policies/b3/. Accessed Feb 5, 2015.
References
- The potential benefit of the placebo effect in sham-controlled trials: implications for risk-benefit assessments and informed consent.J Med Ethics. 2013; 39: 703-707
- Ethical framework for the use of sham procedures in clinical trials.Crit Care Med. 2003; 31: S126-S130
- A controlled trial of arthroscopic surgery for osteoarthritis of the knee.N Engl J Med. 2002; 347: 81-88
- A randomized trial of vertebroplasty for osteoporotic spinal fractures.N Engl J Med. 2009; 361: 569-579
- A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures.N Engl J Med. 2009; 361: 557-568
- Occipital nerve stimulation in fibromyalgia: a double-blind placebo-controlled pilot study with a six-month follow-up.Neuromodulation. 2014; 17: 256-263
- A double-blind, randomized, controlled trial on surgery for chronic abdominal pain due to anterior cutaneous nerve entrapment syndrome.Ann Surg. 2013; 257: 845-849
- Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: the CELLWAVE randomized clinical trial.JAMA. 2013; 309: 1622-1631
- Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion.Am J Ophthalmol. 2014; 157: 237-247.e1
- Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear.N Engl J Med. 2013; 369: 2515-2524
- Transplantation of embryonic dopamine neurons for severe Parkinson's disease.N Engl J Med. 2001; 344: 710-719
- A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease.Ann Neurol. 2003; 54: 403-414
- Randomized surgical trials and “sham” surgery: relevance to modern orthopaedics and minimally invasive surgery.Iowa Orthop J. 2006; 26: 107-111
- Ethics and uncertainty: considerations for the design and review of translational trials involving stem cells.in: Hug K. Hermeren G. Translational stem cell research. Humana Press, Totowa (NJ)2011: 403-418
- Regenerative medicine interventions for orthopedic disorders: ethical issues in the translation into patients.Regen Med. 2013; 8: 65-73
- A proposed definition of regenerative medicine.J Tissue Eng Regen Med. 2007; 1: 179-184
- Stem cell trials for vascular medicine: ethical rationale.Tissue Eng Part A. 2014; 20: 2567-2574
- The reporting of randomized clinical trials using a surgical intervention is in need of immediate improvement: a systematic review.Ann Surg. 2006; 244: 677-683
- The 510(k) ancestry of a metal-on-metal hip implant.N Engl J Med. 2013; 368: 97-100
- Risk of bias of randomized controlled trials published in orthopaedic journals.BMC Med Res Methodol. 2013; 13: 76
- Reporting and methodological quality of systematic reviews in the orthopaedic literature.J Bone Joint Surg Am. 2013; 95: e771-e777
- No surgical innovation without evaluation: the IDEAL recommendations.Lancet. 2009; 374: 1105-1112
- Corporate malfeasance, off-label use, and surgeon liability.Clin Orthop Relat Res. 2013; 471: 4-8
- Why we need observational studies to evaluate the effectiveness of health care.BMJ. 1996; 312: 1215-1218
- Should we be performing more randomized controlled trials evaluating surgical operations?.Surgery. 1995; 118: 459-467
- Sham surgery controls are mitigated trolleys.J Med Ethics. 2005; 31: 149-152
- The ethics of sham surgery in Parkinson's disease: back to the future?.Bioethics. 2013; 27: 175-185
- Sham surgery: an ethical analysis.Sci Eng Ethics. 2004; 10: 157-166
- Challenges and recommendations for placebo controls in randomized trials in physical and rehabilitation medicine: a report of the international placebo symposium working group.Am J Phys Med Rehabil. 2010; 89: 160-172
- Ethics, methodology and the use of placebo controls in surgical trials.Brain Res Bull. 2005; 67: 290-297
- Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment.N Engl J Med. 2001; 344: 1594-1602
- Sham procedure versus usual care as the control in clinical trials of devices: which is better?.Proc Am Thorac Soc. 2007; 4: 574-576
- Is placebo surgery unethical?.N Engl J Med. 2002; 347: 137-139
- Ethical issues in the design of randomized trials: to sham or not to sham.J Bone Joint Surg Am. 2012; 94: 7-10
- Surgery as placebo: a quantitative study of bias. 1961.Int Anesthesiol Clin. 2007; 45: 35-45
- Surgery as a placebo.Lancet. 1994; 344: 1140-1142
- Do medical devices have enhanced placebo effects?.J Clin Epidemiol. 2000; 53: 786-792
- Unnecessary holes in the head.IRB. 2001; 23: 1-6
- The ethics of sham surgery in clinical orthopaedic research.J Bone Joint Surg Am. 2007; 89: 1650-1653
- Is a placebo-controlled surgical trial an oxymoron?.J Minim Invasive Gynecol. 2007; 14: 278-283
- Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.Trials. 2011; 12: 50
- The ethics of sham invasive intervention trials.Clin Trials. 2009; 6: 401-402
- Design and execution of clinical trials in orthopaedic surgery.Bone Joint Res. 2014; 3: 161-168
- Primum non nocere and randomised placebo-controlled surgical trials: a dilemma?.ANZ J Surg. 2009; 79: 508-509
- Sham surgery controls: intracerebral grafting of fetal tissue for Parkinson's disease and proposed criteria for use of sham surgery controls.J Med Ethics. 2002; 28: 322-325
- Sham surgery in research: a surgeon's view.Am J Bioeth. 2003; 3: 65-66
- Randomised clinical trials in surgery: a look at the ethical and practical issues.Indian J Surg. 2011; 73: 245-250
- Double-blind, placebo-controlled trials for surgical interventions in Parkinson disease.Arch Neurol. 2005; 62: 1343-1344
- Placebo interventions, placebo effects and clinical practice.Philos Trans R Soc Lond B Biol Sci. 2011; 366: 1905-1912
- Sham surgery in randomized trials: additional requirements should be satisfied.Am J Bioeth. 2003; 3: W5-W7
- I need a placebo like I need a hole in the head.J Law Med Ethics. 2002; 30: 69-72
- Finnish Degenerative Meniscal Lesion Study (FIDELITY): a protocol for a randomised, placebo surgery controlled trial on the efficacy of arthroscopic partial meniscectomy for patients with degenerative meniscus injury with a novel ‘RCT within-a-cohort’ study design.BMJ Open. 2013; 3
- Sham surgery: not an oxymoron.Am J Bioeth. 2003; 3: W8-W9
- Sham procedures and the ethics of clinical trials.J R Soc Med. 2004; 97: 576-578
- The ethics of placebo-controlled trials: a comparison of inert and active placebo controls.World J Surg. 2005; 29: 610-614
- Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson's disease.N Engl J Med. 1999; 341: 988-992
- The ethics of sham surgery in research.J Vasc Surg. 2003; 37: 482-483
- If the goal is relief, what's wrong with a placebo?.Am J Bioeth. 2003; 3: 53-54
- The enduring legacy of sham-controlled trials of internal mammary artery ligation.Prog Cardiovasc Dis. 2012; 55: 246-250
- Placebos that harm: sham surgery controls in clinical trials.Stat Methods Med Res. 2002; 11: 413-427
- Use of placebo controls in the evaluation of surgery: systematic review.BMJ. 2014; 348: g3253
- Sham surgery and genuine standards of care: can the two be reconciled?.Am J Bioeth. 2003; 3: 61-64
- Placebo or intervention? Is it all a sham?.Anaesthesia. 2011; 66: 73-75
- Invasive ‘placebo’ controls: have we lost sight of whom we are blinding?.Paediatr Anaesth. 2011; 21: 1089-1091
- A critical analysis of evidence for using sham surgery in Parkinson's disease: implications for public health.Aust N Z J Public Health. 2007; 31: 270-274
- Placebo surgery for Parkinson's disease: do the benefits outweigh the risks?.J Law Med Ethics. 2002; 30: 58-68
- The ethical problems with sham surgery in clinical research.N Engl J Med. 1999; 341: 992-996
- Sham neurosurgery in patients with Parkinson's disease: is it morally acceptable?.J Med Ethics. 2001; 27: 151-156
- Misunderstanding in clinical research: distinguishing therapeutic misconception, therapeutic misestimation, and therapeutic optimism.IRB. 2003; 25: 11-16
- Attitudes and beliefs about placebo surgery among orthopedic shoulder surgeons in the United Kingdom.PLoS One. 2014; 9: e91699
- Placebo-controlled procedural trials for neurological conditions.Neurotherapeutics. 2007; 4: 531-536
- Ethical issues of participant recruitment in surgical clinical trials.Ann Surg Oncol. 2013; 20: 3184-3187
- Social aspects of sham surgeries.Am J Bioeth. 2003; 3: 70-71
- Ethical issues in clinical neuroscience research: a patient's perspective.Neurotherapeutics. 2007; 4: 537-544
- Ethics of sham surgery: perspective of patients.Mov Disord. 2008; 23: 63-68
- Use of ‘sham’ radiotherapy in randomized clinical trials.J Med Imaging Radiat Oncol. 2008; 52: 269-277
- The challenge of recruiting patients into a placebo-controlled surgical trial.Trials. 2014; 15: 167
- Science and ethics of sham surgery: a survey of Parkinson disease clinical researchers.Arch Neurol. 2005; 62: 1357-1360
- Studying neurosurgical implants for Parkinson disease: a question of design.Neurology. 2006; 67: 1503-1505
- The physician's role, “sham surgery,” and trust: a conflict of duties?.Am J Bioeth. 2003; 3: 57-58
- The ethics of sham surgery in clinical orthopaedic research.J Bone Joint Surg Am. 2008; 90: 444-445
- Are phase I trials therapeutic? Risk, ethics, and division of labor.Bioethics. 2014; 28: 136-146
- Translating stem cell research: challenges at the research frontier.J Law Med Ethics. 2010; 38: 267-276
- Defining and describing benefit appropriately in clinical trials.J Law Med Ethics. 2000; 28: 332-343
- Deception in research on the placebo effect.PLoS Med. 2005; 2: e262
- Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: ethical and scientific issues.Ann Intern Med. 2000; 133: 455-463
- Placebo orthodoxy in clinical research. II: ethical, legal, and regulatory myths.J Law Med Ethics. 1996; 24: 252-259
World Medical Association. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. 2013. Available from: http://www.wma.net/en/30publications/10policies/b3/. Accessed Feb 5, 2015.
- The ethics of placebo-controlled trials.in: Emanuel E.J. Grady C.C. Crouch R.A. Lie R.K. Miller F.G. Wendler D.D. The Oxford textbook of clinical research ethics. Oxford University Press, Oxford2011
- International Ethical Guidelines for Biomedical Research Involving Human Subjects.WHO, Geneva2002 (Available from: http://www.cioms.ch/publications/layout_guide2002.pdf. Accessed Feb 5, 2015)
- Can it work? Does it work? Is it worth it? The testing of health care interventions is evolving.BMJ. 1999; 319: 652-653
- Blinding in randomised trials: hiding who got what.Lancet. 2002; 359: 696-700
- Placebo surgery research: a blinding imperative.J Clin Epidemiol. 2006; 59: 876-880
- The double-blind, randomized, placebo-controlled trial: gold standard or golden calf?.J Clin Epidemiol. 2001; 54: 541-549
- Medicine, methodology, and values: trade-offs in clinical science and practice.Perspect Biol Med. 2011; 54: 243-255
- Randomised trials in surgery: problems and possible solutions.BMJ. 2002; 324: 1448-1451
- The challenges faced in the design, conduct and analysis of surgical randomised controlled trials.Trials. 2009; 10: 9
- Challenges in evaluating surgical innovation.Lancet. 2009; 374: 1097-1104
- Ethics and evidence based surgery.J Med Ethics. 2004; 30: 160-165
- Bench to bedside: mapping the moral terrain of clinical research.Hastings Cent Rep. 2008; 38: 30-42
- What makes clinical research ethical?.JAMA. 2000; 283: 2701-2711
- The social value of clinical research.BMC Med Ethics. 2014; 15: 66
- Are risks and benefits of oncological research protocols both incommensurable and incompensable?.Account Res. 2007; 14: 179-196
- A framework for risk-benefit evaluations in biomedical research.Kennedy Inst Ethics J. 2011; 21: 141-179
- Assessing research risks systematically: the net risks test.J Med Ethics. 2007; 33: 481-486
- Decision theory and the evaluation of risks and benefits of clinical trials.Drug Discov Today. 2012; 17: 1263-1269
- Money and distorted ethical judgments about research: ethical assessment of the TeGenero TGN1412 trial.Am J Bioeth. 2007; 7: 76-81
Article info
Publication history
Footnotes
Niemansburg was funded by project P2.01 IDiDAS of the research program of the BioMedical Materials institute, co-funded by the Dutch Ministry of Economic Affairs. The financial contribution of the Dutch Arthritis Foundation is gratefully acknowledged. Prof. van Delden is currently the president of the Council for International Organizations of Medical Sciences. He is also a member of the Central Committee of Human Research of The Netherlands and the Dutch Health Council. Prof. Dhert reported research funding by project P2.01 IDiDAS of the research program of the BioMedical Materials institute, co-funded by the Dutch Ministry of Economic Affairs. Prof. Dhert is also a member editorial board “Tissue Engineering,” board member Dutch Program for Tissue Engineering and the Dutch Forum on Regenerative Medicine (DutchFORM) and the Netherlands Institute for Regenerative Medicine (NIRM), member of the AO Research Review Commission (AORRC), member of the Scientific Advisory Board of DSM Biomedical Materials B.V., and Board member of the Smart Mix TeRM ‘Translational Regenerative Medicine’ Program. Dr Bredenoord received research funding by project P2.01 IDiDAS of the research program of the BioMedical Materials Institute, the Netherlands Organisation for Health Research and Development Veni-grant 016.136.093, and the ZonMw Program Priority Medicines for Children. She is also a member of the International Stem Cell Forum Ethics Working Party and the Young Academy of the Royal Netherlands Academy of Arts and Sciences.