Class Six/notes

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Notes 3.13.06 - as always, pls edit/add/correct/etc!

Government: Regulating the Marketplace (PowerPoint)

Beverly H. Lorell

Bkgd:

• Cardiologist, taught at HMS, had lab w/ funding from NIH

• Served as advisor for FDA

• Chief medical officer at Guidant

Postmarket patient-physician environment

• Patient used to have narrow product focus: single clinical challenge, single encounter, single expectation, single heath choice

• Seniors with complex product expectations: complex chronic challenges, long-term encounters, complex expectations, complex health choices

o Usually not direct interaction between MD and patient, guidelines tailored to patient

Industry perspective – pre and postmarket gates

• Introducting new innovation: four questions

o Is the clinical need (market) small or large – to provide enough return to enable research for iterative development

o What are expectations for patient/physician to adopt

o What are premarket challenges

o What are known and emerging postmarket challenges

FDA – industry – patients: Fundamental framework for postmarket regulation

• Big marketplace to regulate

• FDA must be able to deal w/ new technologies, too

• Postmarket regulation is different for devices as opposed to drugs – product cycle is different

o Concept, prototype, preclinical, clinical, manufacturing, marketing, commercial use, obsolescence – not a line, but a circle

o Drugs, by contrast, are written in stone

o Devices are in constant spiral/pipeline that FDA must keep up with

• FDA history: reg of drugs is old, but formal reg of devices is v new (began in 1976)

o Risk-based regulation – not all products are the same

o Premarket/postmarket balance (constant/permanent tension between getting new products to patient quickly and risk of unexpected issues)

o Facilitate innovation and patient access

o Rapid evolution of device technology

o Recognition of small business segment

• Imp amendments in 1976:

o Risk-based classification (Class I, II, III)

o If in Class III, must get PMA (reasonable assurance of safety & efficacy)

o If in Class I or II, must be able to show substantial equiavalence

• Led to development of adverse event reporting (birth of the MDR)

• 1990 Safe Medical Device Act – resulted from four events, include TSS and Shiley Heart Valve (challenge of rare and late safety event that affected large pop)

o Shift back for larger surveillance of postmarket safety

o Demanded for first time that hospitals had mandatory reporting to manuf and govt if defective perf of medical device

o FDA thinks these new authorities are just realizing their potential

• FDAMA (1997) and MDFUMA (2002): shift focus back to premarket activities (acceleration of innovation and patient access) (for summary of medical device reporting, go here)

o Recog standard, least burdensome, third party review

o User fees

• Diff between device and drug: user (hospital) reporting, superceding patient privacy to track devices, mandatory recalls

• Regulating entry to market: long time, huge investment

• Once in market, two streams: active and passive surveillance

o We’re focusing on passive: labeling, adverse event reporting, making corrections, emp by FDA clout and expectation that manuf will act properly

o Labeling: anything manuf disseminates ab the product – provides imp safety info

o Branding: FDA is concerned ab what a manuf says/does not say

o Passive safety surveillence: grounded in MDR – intent of Congress and FDA is to cast a v wide net (may have caused/might eventually cause); mandatory for manuf, importers, and hospitals, but voluntary for physician, caregiver, office/home-based

- Manuf are on a clock –challenging bc many sources, many adverse events need more high level clinical info

- Limits: underreporting, hard to get accurate source docs, can’t get device back, physician reporting voluntary, barrier from misinterp ab patient privacy and fear of litig

- Public access: FDA is permitted by law to release these reports, most MDRs are from industry, but diff to translate into transparency

o Quality systems regs: v diff from framework for drugs, makes sure meets specs and manuf is in control of process

- Most imp is corrective and preventative actions (CAPA) – requires investigating cause of nonconformities, actions defined to correct problems with verification and implementation

• Diff from drugs bc can make changes in months rather than yrs – purpose is to link postmarket learning w/ correcting design/manuf process

- Trend and root case analysis involving statistics, engineers, and scientists

- Manuf must be able to track and trace every device and all its components during lifetime – expected by FDA

- Corrections/removal – repair, modification, relabeling, removal

- Recall – correction or removal when FDA finds reasonable probability of serious, adverse health conseq or death, does not always mean removal of device – virtually all are voluntary

• FDA does risk assessment, health hazard evaluation, can do mandatory recall (Class I recall is highest risk)

- Notifications – FDA requires communication, manuf and FDA both do press releases, replacing dear dr letters and perhaps leading to miscommunication or influencing choice of new product

o Communications tensions: patients, doctors, and market – oblig of ethical oblig for informed patient choice (when, sequence, notification, info)

Changing FDA and public expectations: The Elephants in the Room

• Expectations for postmarket reliability and safety do change during device innovation life cycle

o As market size/target pop expands, so does public health impact, which leads to higher public and reg expectations

• Tension between reg, industry, and public expectations for device reliability and freedom from low-frequency serious safety events

o Trials are designed for v specific purpose

o Even among drs, huge variation in expectation/behaviors

• Five elephants for life-sustaining devices w/ malfunctions w/ potential to cause death or serious injury

o Do numbers count?

o If numbers count, what number? Change from indiv patients to pop

o Do actual deaths count more than risk of deaths?

o Are changes required in existing law or interp of law to enhance postmarket adverse event reporting? Lorell thinks we are stuck w/ making law better

o Continuous manuf improvements: when/how should changes be publicly disclosed and what level of confid is needed?

Bruce’s question: device statute preempts state law for product liability; drug manuf who goes through all the same steps is still on hook for product liability. When you compare the two industries, what is the diff in incentives to comply?

Discussion:

• For both drugs and devices, when is enough testing enough?

o What ab hybrids?

o Should there be a diff dep on size of target pop, type of health risk?

• Who is the elephant keeper? Industry? Academic/physician? Govt/FDA?

o Easiest soln would be for FDA to be keeper

o But FDA makes clear that it expects industry to do a lot

o Physician societies are also v involved, have a diff style of reporting

o Direct to patient info – who’s job is it to corral this?

- Bruce’s theory that direct to patient ads usu in long term treatments, less likely in device context

- Lorell’s response: in device industry, more direct to patient ads are implants bc such a huge decision to make – different commitment to product

- Media info is v powerful when problem is recognized (e.g. stents)

• What is role of indiv patient as keeper? Ripe opp for enhancing sys, but v infrequent (MedWatch, patient advocacy groups)

• How has informed consent evolved?

o Upfront expectation to be told in lang you understand the risks of procedure and long-term risks

o For devices and drugs w/ v long term uses, need mechanism to give patient new info when learned (v hard task for physicians to inform every patient, esp when infrequent problem)

- Companies must make decisions on when to communicate

- Guidant assembled indep panel to advise them ab this issue after a problem w/ device

o Easier to describe early risks than long-term potential risks, but still expectation for investigation of and action concerning specific, systemic problem

Belee 21:25, 13 March 2006 (EST)

See Also

• Discussion Generated by the Question Tool here