Informing Care Decisions: Emerging Technologies, Scientific Evidence, and Communication

1. Informing Care Decisions: Emerging Technologies, Scientific Evidence, and Communication Elise Berliner, PhD Director, Technology Assessment Program Center for Outcomes and Evidence

3. 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

5. Historical Example: Autologous Bone Marrow Transplantation (ABMT) • Rescue from high dose chemotherapy with autologous bone marrow transplantation in patients with breast cancer • Reviews of uncontrolled trials in 1988-1989 found response rates (tumor shrinkage) of 58-80% • 1990: preliminary results of Phase II study showed 40% improvement in three year survival rates compared with historical controls treated with standard-dose chemotherapy Sources: Welch and Mogielnicki 2002 BMJ 324:1088-1092; Mello and Brennan 2001 Health Affairs20:101-117

6. ABMT History Continued • Methodological problems with studies • Uncontrolled • Selection bias: selection criteria for ABMT stricter than historical studies of standard dose chemotherapy • ABMT trial participants had demonstrated an objective response to previously administered chemotherapy • Short follow up time • Small sample size • Potential adverse effects Source: Mello and Brennan 2001 Health Affairs20:101-117

7. ABMT History Continued • Many insurance companies defined ABMT as “experimental” • No clear and consistent definition of “experimental” • Lawsuits for coverage • Massachusetts federal judge (1990): “To require that the plaintiff or other plan members wait until somebody chooses to present statistical proof …that would satisfy all the experts means that plan members would be doomed to receive medical procedures that are not state of the art”. REFERENCE: Welch and Mogielnicki 2002 BMJ 324:1088-1092

8. ABMT History Continued • 1996 GAO report: “Coverage of Autologous Bone Marrow Tranplantation for Breast Cancer • “Although it is widely considered an experimental therapy, many health insurers are covering ABMT following high-dose chemotherapy for breast cancer” • Coverage policies influenced by fear of litigation and adverse public relations • Use increased rapidly from estimated 522 patients in 1989 to an estimated 4,000 in 1994 • Four controlled clinical trials funded by NCI • Enrollment slower than expected • “We worry that women are not enrolling in these clinical trials because they mistakenly assume that HDC-ABMT is already a proven treatment and because they can receive it outside of studies” Dr. Jeffrey Abrams, NCI • Slow enrollment leads to delay in research results SOURCES: GAO/HEHS-96-83 and press release at http://www.hhs.gov/news/press/1996pres/960528.html

9. ABMT History Continued • Four RCTs presented at 1999 meeting of the American Society of Clinical Oncology meeting did not support use of ABMT • NEJM editorial in 2000: “To a reasonable degree of probability AMBT for metastatic breast cancer has been proved to be ineffective and should be abandoned” • Effect on patients • Estimated 42,680 ABMT procedures between 1990-1999 • Acute toxicities: sepsis, pulmonary failure, veno-occlusive disease, cardiac failure, nephrotoxicity, hemorrhagic cystitis and cardiac toxicity • Chronic toxicities: acute myelogenous leukemia or myelodysplastic syndrome, bone marrow insufficiency, heightened vulnerability to opportunistic infections in the first year • Treatment related mortality rates up to 7% in controlled trials. Sources: Welch and Mogielnicki 2002 BMJ 324:1088-1092; Mello and Brennan 2001 Health Affairs20:101-117

10. Particle Beam Therapy for Cancer 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

11. Particle Beam Therapy For Cancer Study Design “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.

12. Particle Beam Therapy For Cancer Table A. Comparators assessed in the randomized controlled trials 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.

13. Particle Beam Therapy for Cancer • “In an ideal world, some oncologists say, most cancer patients would get 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” (US News and World Report, April 2008) • “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 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 tumor” (NYTimes, December 26, 2007) • “The scientific debate could be resolved with a large trial in which 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 of physics prove beyond a shadow of a doubt that proton radiation" is better, insists prostate cancer survivor Robert Marckini of Mattapoisett, Mass.” (Forbes, March 16, 2009).

14. Radiofrequency Catheter Ablation for Atrial Fibrillation http://www.healthline.com/sw/hr-nl-atrial-fibrillation-beyond-drug-therapies

15. Radiofrequency Catheter Ablation for Atrial Fibrillation • Many different types of catheters • First two catheters specifically approved for atrial fibrillation by the FDA in Feb. 2009 • Many other catheters used “off-label” by physicians • Many different variations of the procedure • Different areas of the heart ablated • Different imaging techniques to guide the procedure (flouroscopy, MRI, CT, electroanatomic navigation) • Evidence is lacking to determine which of these variations would work best in different patients

16. Radiofrequency Catheter Ablation for Atrial Fibrillation • Reduces recurrence of atrial fibrillation when used as 2nd line therapy but studies only had short follow-up (≤12 mo) • No long term evidence on mortality etc. • Low level of evidence on quality of life (methodological deficiencies in primary studies) • Insufficient data on use as 1st line therapy • Major clinical complications <5%, but quality of data is poor • non-uniform definitions and assessments • Need more data on the elderly, patients with multiple co-morbidities, long-term (years) rates of AF recurrence, effects from radiation exposure, QOL, and mortality

17. Radiofrequency Catheter Ablation 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

18. Conclusions • Premature adoption of new technologies outside of clinical trials might lead to harm • The portrayal of the state of scientific evidence surrounding new medical technologies is often exaggerated by the physicians, patients and journalists. • Some technologies (such as catheter ablation) have less hype than others (such as proton beam)

19. Contact Elise Berliner elise.berliner@ahrq.hhs.gov 301-427-1612