Transcript Sham Surgery - Purdue University

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 carotidartery 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 surgeryrelated 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.