informing care decisions: emerging technologies, scientific evidence, and communication
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Informing Care Decisions: Emerging Technologies, Scientific Evidence, and Communication. Elise Berliner, PhD Director, Technology Assessment Program Center for Outcomes and Evidence. http://blogs.amctv.com/scifi-scanner/2009/01/star-trek-ultrasonic-medical-device.php. - PowerPoint PPT PresentationTRANSCRIPT
Informing Care Decisions: Emerging Informing Care Decisions: Emerging Technologies, Scientific Evidence, and Technologies, Scientific Evidence, and
Communication Communication
Elise Berliner, PhDElise Berliner, PhD
Director, Technology Assessment ProgramDirector, Technology Assessment Program
Center for Outcomes and EvidenceCenter for Outcomes and Evidence
http://blogs.amctv.com/scifi-scanner/2009/01/star-trek-ultrasonic-medical-device.phphttp://blogs.amctv.com/scifi-scanner/2009/01/star-trek-ultrasonic-medical-device.php
Historical Example: Autologous Bone Historical Example: Autologous Bone Marrow Transplantation (ABMT)Marrow Transplantation (ABMT)
Rescue from high dose chemotherapy with Rescue from high dose chemotherapy with autologous bone marrow transplantation in autologous bone marrow transplantation in patients with breast cancerpatients with breast cancer
Reviews of uncontrolled trials in 1988-1989 Reviews of uncontrolled trials in 1988-1989 found response rates (tumor shrinkage) of 58-found response rates (tumor shrinkage) of 58-80% 80%
1990: preliminary results of Phase II study 1990: preliminary results of Phase II study showed 40% improvement in three year showed 40% improvement in three year survival rates compared with historical controls survival rates compared with historical controls treated with standard-dose chemotherapytreated with standard-dose chemotherapy
Sources: Welch and Mogielnicki 2002 BMJ 324:1088-1092; Mello and Sources: Welch and Mogielnicki 2002 BMJ 324:1088-1092; Mello and Brennan 2001 Health Affairs20:101-117Brennan 2001 Health Affairs20:101-117
ABMT History ContinuedABMT History Continued
Methodological problems with studiesMethodological problems with studies– UncontrolledUncontrolled– Selection bias: selection criteria for ABMT stricter Selection bias: selection criteria for ABMT stricter
than historical studies of standard dose than historical studies of standard dose chemotherapychemotherapy ABMT trial participants had demonstrated an objective ABMT trial participants had demonstrated an objective
response to previously administered chemotherapyresponse to previously administered chemotherapy
– Short follow up timeShort follow up time– Small sample sizeSmall sample size
Potential adverse effectsPotential adverse effects
Source: Mello and Brennan 2001 Health Affairs20:101-117Source: Mello and Brennan 2001 Health Affairs20:101-117
ABMT History ContinuedABMT History Continued
Many insurance companies defined ABMT as Many insurance companies defined ABMT as “experimental”“experimental”– No clear and consistent definition of No clear and consistent definition of
“experimental”“experimental” Lawsuits for coverageLawsuits for coverage
– Massachusetts federal judge (1990): “To require Massachusetts federal judge (1990): “To require that the plaintiff or other plan members wait until that the plaintiff or other plan members wait until somebody chooses to present statistical proof …somebody chooses to present statistical proof …that would satisfy all the experts means that plan that would satisfy all the experts means that plan members would be doomed to receive medical members would be doomed to receive medical procedures that are not state of the art”.procedures that are not state of the art”.
REFERENCE: Welch and Mogielnicki 2002 BMJ 324:1088-1092REFERENCE: Welch and Mogielnicki 2002 BMJ 324:1088-1092
ABMT History ContinuedABMT History Continued 1996 GAO report: “Coverage of Autologous Bone 1996 GAO report: “Coverage of Autologous Bone
Marrow Tranplantation for Breast Cancer Marrow Tranplantation for Breast Cancer – ““Although it is widely considered an experimental therapy, Although it is widely considered an experimental therapy,
many health insurers are covering ABMT following high-dose many health insurers are covering ABMT following high-dose chemotherapy for breast cancer”chemotherapy for breast cancer”
– Coverage policies influenced by fear of litigation and adverse Coverage policies influenced by fear of litigation and adverse public relationspublic relations
– Use increased rapidly from estimated 522 patients in 1989 to Use increased rapidly from estimated 522 patients in 1989 to an estimated 4,000 in 1994an estimated 4,000 in 1994
Four controlled clinical trials funded by NCIFour controlled clinical trials funded by NCI– Enrollment slower than expectedEnrollment slower than expected– ““We worry that women are not enrolling in these clinical trials We worry that women are not enrolling in these clinical trials
because they mistakenly assume that HDC-ABMT is already because they mistakenly assume that HDC-ABMT is already a proven treatment and because they can receive it outside of a proven treatment and because they can receive it outside of studies” Dr. Jeffrey Abrams, NCIstudies” Dr. Jeffrey Abrams, NCI
– Slow enrollment leads to delay in research resultsSlow enrollment leads to delay in research results
SOURCES: GAO/HEHS-96-83 and press release at SOURCES: GAO/HEHS-96-83 and press release at http://www.hhs.gov/news/press/1996pres/960528.htmlhttp://www.hhs.gov/news/press/1996pres/960528.html
ABMT History ContinuedABMT History Continued
Four RCTs presented at 1999 meeting of the American Four RCTs presented at 1999 meeting of the American Society of Clinical Oncology meeting did not support use Society of Clinical Oncology meeting did not support use of ABMTof ABMT
NEJM editorial in 2000: “To a reasonable degree of NEJM editorial in 2000: “To a reasonable degree of probability AMBT for metastatic breast cancer has been probability AMBT for metastatic breast cancer has been proved to be ineffective and should be abandoned”proved to be ineffective and should be abandoned”
Effect on patientsEffect on patients– Estimated 42,680 ABMT procedures between 1990-1999Estimated 42,680 ABMT procedures between 1990-1999– Acute toxicities: sepsis, pulmonary failure, veno-occlusive Acute toxicities: sepsis, pulmonary failure, veno-occlusive
disease, cardiac failure, nephrotoxicity, hemorrhagic cystitis and disease, cardiac failure, nephrotoxicity, hemorrhagic cystitis and cardiac toxicitycardiac toxicity
– Chronic toxicities: acute myelogenous leukemia or Chronic toxicities: acute myelogenous leukemia or myelodysplastic syndrome, bone marrow insufficiency, myelodysplastic syndrome, bone marrow insufficiency, heightened vulnerability to opportunistic infections in the first yearheightened vulnerability to opportunistic infections in the first year
– Treatment related mortality rates up to 7% in controlled trials. Treatment related mortality rates up to 7% in controlled trials.
Sources: Welch and Mogielnicki 2002 BMJ 324:1088-1092; Mello and Brennan 2001 Health Sources: Welch and Mogielnicki 2002 BMJ 324:1088-1092; Mello and Brennan 2001 Health Affairs20:101-117Affairs20:101-117
Particle Beam Therapy for Particle Beam Therapy for CancerCancer
Redrawn schematic of a proton therapy center. Adapted from a schematic of the Rinecker Proton Therapy Center, RPTC, Munich, Germany, under construction by ACCEL Instruments (http://www.proton-therapy.com; last accessed 06/16/2008).
The six images above compare the dose distribution of X-ray beams with proton beams.. Red is the maximum dose, followed by orange, yellow, green, blue, and purple..
From
http://www.pi.hitachi.co.jp/rd-eng/product/industrial-sys/accelerator-sys/proton-therapy-sys/proton-beam-therapy/index.html
Particle Beam Therapy For Particle Beam Therapy For CancerCancer
“When I was doing semiconductor device research, it was expected that I would compare my results with other people's previously published results and that I would comment on any differences. But it seemed to be different in medicine. Medical practitioners primarily tended to publish their own data; they often didn't compare their data with the data of other practitioners, even in their own field, let alone with the results of other types of treatments for the same condition. So I kept on doing cross-comparisons as best I could. “
Andy Grove, cofounder of Intel and prostate cancer patient, Fortune Magazine, May 13, 1996.
Cancer type Single arm RCTs Nonrandomized comparative
Total
Ocular 80 4 7 91
Head/neck 53 2 1 56
Spine 9 0 0 9
GI 18 1 2 21
Prostate 14 3 2 19
Bladder 3 0 0 3
Uterus 4 0 1 5
Bone/soft tissue
6 0 0 6
Lung 17 0 0 17
Breast 2 0 0 2
Miscellaneous 14 0 0 14
Study Design
Particle Beam Therapy For Particle Beam Therapy For CancerCancer
Table A. Comparators assessed in the randomized controlled trials
Cancer type and centerComparison N Survival
(overall/ specific)
Ocular (uveal melanoma)
MGH (US) Higher vs. lower dose proton RT 188 No/No
UCSF (US) Helium RT vs. I-125 brachytherapy 136; 184 Yes/Yes
CPO (France) Proton RT vs. proton RT + laser TTT 151 Yes/Yes
Head/neck (skull base chordoma/chondrosarcoma)
MGH (US) Higher vs. lower dose proton RT 96 Yes/No
Head/neck (brain glioblastoma)
UCSF (US) Higher vs. lower dose proton RT 15 Yes/Yes
GI (pancreatic cancer)
UCSF (US) Helium RT vs. photon RT 49 Yes/Yes
Prostate
MGH and LLU (US) Photon RT + standard-dose proton vs. photon RT + high-dose proton
393 Yes/Yes
MGH (US) Photon RT + local photon boost vs. photon RT + local proton boost
202; 191 Yes/Yes
Abbreviations: CPO=Centre de protonthérapie d'Orsay; GI=gastrointestinal; LLU=Loma Linda University; MGH=Massachusetts General Hospital; N=number of enrolled patients; RT=radiotherapy; TTT=transpupillary thermotherapy UCSF=University of California San Francisco.
Particle Beam Therapy for Particle Beam Therapy for CancerCancer
““In an ideal world, some oncologists say, most cancer patients would get In an ideal world, some oncologists say, most cancer patients would get this rare type of treatment, in which doctors use nuclear technology and this rare type of treatment, in which doctors use nuclear technology and magnets to fire protons into tumors at about two thirds the speed of light” magnets to fire protons into tumors at about two thirds the speed of light” (US News and World Report, April 2008)(US News and World Report, April 2008)
““It all comes down to the physics,” said Dr. Jerry D. Slater, the head of It all comes down to the physics,” said Dr. Jerry D. Slater, the head of radiation medicine at Loma Linda University Medical Center in Southern radiation medicine at Loma Linda University Medical Center in Southern California. “Every X-ray beam I use puts most of the dose where I don’t California. “Every X-ray beam I use puts most of the dose where I don’t want it.” By contrast, he said, proton beams put most of the dose in the want it.” By contrast, he said, proton beams put most of the dose in the tumor” (NYTimes, December 26, 2007)tumor” (NYTimes, December 26, 2007)
““The scientific debate could be resolved with a large trial in which The scientific debate could be resolved with a large trial in which patients were randomly assigned to X-rays or protons and tracked for patients were randomly assigned to X-rays or protons and tracked for years. Proton proponents say that would be a waste of time. "The laws years. Proton proponents say that would be a waste of time. "The laws of physics prove beyond a shadow of a doubt that proton radiation" is of physics prove beyond a shadow of a doubt that proton radiation" is better, insists prostate cancer survivor Robert Marckini of Mattapoisett, better, insists prostate cancer survivor Robert Marckini of Mattapoisett, Mass.” (Forbes, March 16, 2009). Mass.” (Forbes, March 16, 2009).
Radiofrequency Catheter Radiofrequency Catheter Ablation for Atrial FibrillationAblation for Atrial Fibrillation
http://www.healthline.com/sw/hr-nl-atrial-fibrillation-beyond-drug-therapies
Radiofrequency Catheter Radiofrequency Catheter Ablation for Atrial FibrillationAblation for Atrial Fibrillation
Many different types of cathetersMany different types of catheters– First two catheters specifically approved for atrial First two catheters specifically approved for atrial
fibrillation by the FDA in Feb. 2009 fibrillation by the FDA in Feb. 2009 – Many other catheters used “off-label” by Many other catheters used “off-label” by
physiciansphysicians Many different variations of the procedureMany different variations of the procedure
– Different areas of the heart ablatedDifferent areas of the heart ablated– Different imaging techniques to guide the Different imaging techniques to guide the
procedure (flouroscopy, MRI, CT, procedure (flouroscopy, MRI, CT, electroanatomic navigation)electroanatomic navigation)
Evidence is lacking to determine which of Evidence is lacking to determine which of these variations would work best in different these variations would work best in different patientspatients
Radiofrequency Catheter Radiofrequency Catheter Ablation for Atrial FibrillationAblation for Atrial Fibrillation
Reduces recurrence of atrial fibrillation when used as Reduces recurrence of atrial fibrillation when used as 22ndnd line therapy but studies only had short follow-up line therapy but studies only had short follow-up ((≤12 mo)≤12 mo)– No long term evidence on mortality etc. No long term evidence on mortality etc.
Low level of evidence on quality of life Low level of evidence on quality of life (methodological deficiencies in primary studies)(methodological deficiencies in primary studies)
Insufficient data on use as 1Insufficient data on use as 1stst line therapy line therapy Major clinical complications <5%, but quality of data is Major clinical complications <5%, but quality of data is
poorpoor– non-uniform definitions and assessmentsnon-uniform definitions and assessments
Need more data on the elderly, patients with multiple Need more data on the elderly, patients with multiple co-morbidities, long-term (years) rates of AF co-morbidities, long-term (years) rates of AF recurrence, effects from radiation exposure, QOL, recurrence, effects from radiation exposure, QOL, and mortalityand mortality
Radiofrequency Catheter Radiofrequency Catheter Ablation for Atrial FibrillationAblation for Atrial Fibrillation
“Success rates are good, particularly for patients with intermittent atrial fibrillation, but some patients require repeat procedures and some still need to take medications afterward. Patients with persistent atrial fibrillation have lower success rates. Some serious complications can occur with this procedure, so the risks and potential benefits must be carefully weighed.”
Tampa Tribune 2008
"I think they're successful maybe in the 80 percent range, but not like we'd like - which would be up in the high 90s," [Dr. R Dent Underwood] said. "But if you look back 10 years ago, it wasn't even an option."
St. Paul Pioneer Press February 2008
ConclusionsConclusions
Premature adoption of new technologies Premature adoption of new technologies outside of clinical trials might lead to harmoutside of clinical trials might lead to harm
The portrayal of the state of scientific The portrayal of the state of scientific evidence surrounding new medical evidence surrounding new medical technologies is often exaggerated by the technologies is often exaggerated by the physicians, patients and journalists.physicians, patients and journalists.– Some technologies (such as catheter ablation) Some technologies (such as catheter ablation)
have less hype than others (such as proton have less hype than others (such as proton beam)beam)
