SOC 573 - Sham Surgery

James G. Anderson, Ph.D.

Purdue University

Need for Surgical Clinical Trials

• Surgical procedures are frequently introduced into practice on the basis of uncontrolled studies.

• It is estimated that only 7 % of surgical studies use a randomized study design of any type.

Discontinued Surgical Procedures

• Blood letting

• Routine tonsillectomy

• Routine circumcision

• Repeated cesarean delivery

• Internal thoracicartery ligation

• Gastric freezing

• Jejunoilal bypass for obesity

Discontinued Surgical Procedures

• Glomectomy for asthma

• Prophylactic portacaval shunting

• Laparotomy for TB, peritonitis, PID

• Adrenalectomy for essential hypertension

• Extracranial/Inracranial bypass for carotid-artery occlusion

Question

• If we accept a placebo in medicine and drug trials, why don’t we accept it in surgical trials?

Double-Blind Placebo-Controlled Trials

• Should address important research questions.

• Alternative design that imposes lower risks is not available.

• Preliminary evidence of the intervention’s effectiveness is available.

• Treatment should not become obsolete before the study is completed.

Double-Blind Placebo-Controlled Trials

• Risk to participants must be minimized.• Study design should be sufficient to answer the

research questions.• Study participants should provide informed

consent.• Potential benefits should outweigh risks.• Withholding therapy should not pose

unreasonable risk.

History of Sham Surgery

• 1939 Italian surgeon named Fieschi treated angina by trying to increase blood flow to the heart.

• 1959 NIH supports test of the “Fieschi technique.”• 1999 Fetal cell transplants for Parkinson’s disease.• 1999 Treatment for cancer pain by inserting

capsules at the base of the spine.

History of Sham Surgery

• 1999 Arthroscopic surgery for osteoarthritis.

• 1999 Injection of pig cells into the brain of Parkinson's disease patients.

• 2000 Study of intradiscal electrothermal annuloplasty to relieve back pain.

Driving Forces

• NIH and the FDA are anxious to obtain decisive research on controversial new treatments involving the implantation of human or animal cells.

• In 1994 NIH funded the Colorado trial fetal tissue transplants for Parkinson’s disease.

Driving Forces

• The FDA suggested that two Massachusetts companies studying implantation of pig fetal cells for Parkinson’s disease use sham surgery for evaluation.

• The American Association of Neurological Surgeons supports the use of sham surgery in research.

Characteristics of the Use of Placebos in Clinical Research

• Drugs are introduced for specific purposes with known chemical compounds after testing for toxicity and side effects.

• Drug effects are not subject to the physician’s skill or experience.

• Placebos are usually harmless compounds in drug studies.

Characteristics of the Use of Sham Surgery

• Trials that are designed to test surgical procedures are difficult to standardize.

• Outcomes can be significantly affected by differences in physician's skills and organizational arrangements.

• Surgical techniques and devices undergo continuous change due to scientific advances

• Sham surgery is invasive and involves significant risks to patients.

Arguments in Favor of Sham Surgery

• Since 30% of patients show improvements after receiving a placebo, we should study the phenomenon.

• Most surgical procedures have not received rigorous testing and many are applied inappropriately.

• Double-blind placebo-controlled trials will push surgery toward the “gold standard” of clinical testing.

Arguments in Favor of Sham Surgery

• Studies using sham surgery are designed to establish conclusively whether a surgical procedure is safe and effective.

• If the new procedure doesn’t work thousands of patients will be spared the risk and costs.

• Cellular therapies have more in common with the assessment of pharmaceutical agents than conventional surgery.

Arguments against Sham Surgery

• Risks from anesthesia, antibiotics and surgery-related infections outweigh the benefits gained from sham surgery.

• It is morally and ethically wrong to intentionally deceive patients.

• In cases of fatal diseases like Parkinson’s the severity of the disease is coercive rendering informed consent invalid.

Arguments against Sham Surgery

• It is difficult to accurately assess the relative risks and benefits of studies involving sham surgery.

• Withholding a treatment that may be beneficial to a patient is unethical.

• Deception in research is unethical.

Case Study A• A study is being proposed to test a new treatment to

reduce or eliminate spinal disc pain. The technique is called intradiscal electrothermal annuloplasty. The study calls for the random assignment of participants to a study group or control group. The study group will be subjected to surgery involving heating n injured spinal disc with an injected catheter in an attempt to cauterize damaged nerves and repair tears. The control group will be subjected to a sham version of the surgery during which the catheter will be inserted but not heated.

Case Study B• A clinical trial is proposed to test an

experimental therapy for pain in patients with cancer patients in the experimental group would have capsules containing an analgesic inserted into a space at the base of the spine by means of a lumbar puncture. The patents assigned to the control group would have a capsule containing an inert substance inserted. Research subjects will be advised that there is a low risk of permanent nerve injury or paralysis.

Questions• Does this study meet the criteria for a

double-blind placebo controlled trial? If not, why?

• How does this study differ form a research study that involves a pharmacological agent?

• Can the study design be modified to make it acceptable? If so, how?

Questions• List the risks and benefits of this research.

Do the benefits outweigh the risks?

• Is it paternalistic to protect research subjects from risks they are willing to accept?

• When little is known about a experimental treatment such as this one, can patients be accurately appraised of the potential risks when signing a consent form?

Questions• Can investigators and institutional review

boards accurately weigh the potential benefits and risks of studies involving sham surgeries?

• Are there surgical procedures for which it would be appropriate to evaluate using sham surgery? Name some. Are there other procedures where sham surgery would be inappropriate? Name some.