Is FDA failing us Or are we failing FDA? Jonathan C. Javitt, M.D.,M.P.H Senior Fellow, Potomac...

Is FDA failing us

Or are we failing FDA?

Jonathan C. Javitt, M.D.,M.P.HSenior Fellow, Potomac Institute for Policy StudiesFormer Chair, Health Subcommittee, President’s Information Technology Advisory Committee,

Jonathan C. Javitt, M.D., M.P.H.: NEI/FDA Endpoints Meeting. November 28, 2006

Don’t take my word for it

•Our [FDA’s] approach to risk management includes finding ways to help make sure that drugs we review are used safely once they’re approved.

•Too often, the drugs, devices, and other products we regulate are involved in preventable adverse events.

•As many as 20% of Americans have experienced some kind of medical error.

•Preventable errors and complications involving prescription drugs alone are responsible for thousands of deaths, millions of hospitalizations, and billions of dollars in additional health care costs each year, not to mention the unnecessary suffering.

Mark McClellan, M.D., Ph.D.

A seemingly vicious circle

Too few NME’s will be approved this year The cost of bringing new drugs to market is far

too high and takes too long Congress and the public have labeled FDA’s drug

safety process as fundamentally flawed The more pressure that is brought to bear on FDA

to improve drug safety, the more risk averse the agency becomes

Nobody ever got fired from FDA for witholding approval on safety grounds

Jonathan C. Javitt, M.D., M.P.H.: ASENT 2008

The other side of the coin

The real threat to American lives is not dangerous drugs, but rather errors in the use of generally safe and effective drugs

More Americans are harmed by their failure to receive a needed drug than will ever be harmed by administration of a harmful drug

The problem lies in the disconnect between postmarketing surveillance, pharmaceutical risk management, and clinical practice



Today’s question

What is the best way to ensure public safety once drugs are introduced to the marketplace?

Yesterday’s answer anecdotal reporting Today’s answer database analysis Tomorrow’s answer sentinel systems

A Unified Sentinel System: transforming a vicious circle into a virtuous one


A Sentinel System

Continuously monitors all available sources of medical information in order to identify:1.Common medical errors2.Drug adverse events and interactions3.Failure to comply with care4.Threatening clinical parameters5.Opportunities to improve care


GAO Recognizes the problem

However the proffered solutionwill add enormous cost to the regulatory process and provide far less benefit than might otherwise be achieved

GAO does realize, however, that anecdotal reporting databases for drug complications are inherently flawed and that population surveillance is needed


Drug SafetyHealth Plan Records Seen as Cost-EffectiveW ay to Identify Risks of Drugs on Market

Analyzing large health plan databases to detect drug side effects would be a more cost-effective way to monitor drug safety than the risk-minimization plans proposed in a Senate bill (S. 484), a former head of the Food and Drug Administration said recently. Mark McClellan, the former commissioner of FDA, said that he supports S. 484, the drug-safety legislation sponsored by the chairman and ranking member of the Senate Health, Education, Labor, and Pensions Committee, calling it "the right foundation to build on." However, he and others who spoke March 21 at a Capitol Hill briefing cast doubt on whether the legislation makes use of the best type of postmarket drug-safety surveillance


As Safety concerns mount, sponsors have three basic alternatives

10,000 – 100,000 person safety trials prior to market approval Cost prohibitive

Construction of ad-hoc registry programs for each newly launched drug Extremely expensive

Deploy Sentinel Database systems in order to monitor drug safety and utilization $.50 pmpm


The drug safety paradigm must change

While reporting databases can, and should be used to report rare, life-threatening events, moving to active surveillance systems enables us to:

Actively keep drugs safe in the marketplace Improve patient safety by identifying those who

would benefit from therapies they are not receiving

Potentially launch new drugs much more quickly into a monitored environment


The Same Framework that

addresses the most critical problems

confronting patient care, also

addresses the challenges facing

postmarket surveillance and drug approval


The Active Health Care Engine®

HospitalClaims

Lab Results

PharmacyClaims

ProviderClaims

RN Notes

7. Action by Doctor and Patient

4. Apply Medical Intelligence

Clinical Rules

5. Create Recommendations

6. Communicate Recommendations

Letters

Automated

Clinical Review System

Com

mu

nic

ati

on

P

ort

al

MD / RN Review

16 millioncovered

lives


Can deployed Sentinel Systems save lives and save cost?

100,000 member midwestern managed care plan

Selected all members with at least one physician visit and one pharmacy claim in preceeding 12 months

20,000 members selected per group Random allocation to Sentinel system with

mailed clinical prompts or to watchful waiting Study period of 12 months


Implementation of Recommendations

Adoption Care Consideration Description

86% Improve a subtherapeutic INR73% Normalize high INR63% Monitor for toxicity in amiodarone use58% Stop NSAID in anticoagulation56% Stop either Viagra or nitrates50% Monitor INR with interacting drugs46% Monitor INR in Coumadin use44% Stop Wellbutrin in patients with seizures42% Monitor LFTs in patients on glitazones38% Monitor for toxicity in methotrexate use37% Stop metformin in patient with renal insufficiency.


Randomized Prospective Study:

Control Study Difference

Total Admissions 1052 936 11%*

Admits/1000 47.55 42.1 11%*

Hospital Bed-Days total 4089 3483 15%*

ALOS 3.89 days 3.72 days 4.5%*

Days per 1000 184.8 156.9 15%**

Total paid $31.3 MM $29.6 MM 5.5%**

Inpatient paid $4.6 MM $4.1 MM 11%**

* p<.03** p<.005

Approximately 1,000 interventions issued in the intervention group and a similar number observed in the control group

Overall cost saving of 6% - 8%


Sentinel Systems in Postmarketing Surveillance

Reinventing the concept of drug safety– Keeping drugs safe in the marketplace through early detection

of adverse events• Enables early intervention

• Enables early implementation of monitoring

• Enables early labeling changes

– Keeping drugs safe in the marketplace by avoiding interactions and proactive notifying caregivers

– Keeping drugs safe by ensuring clinical monitoring– Keeping patients safe by increasing compliance with therapy– Keeping patients safe by identifying those in need of

unprescribed therapy

Sentinel Systems will actually Increase appropriate sales of lifesaving drugs

Half of those who would benefit from beta blockers post MI are not receiving them

Half of those who qualify for ACE inhibitors under the HOPE trial criteria do not receive them

And so on…



Keeping Drugs Safe in the Marketplace

When Rezulin was approved for the treatment of diabetes, the possibility of liver failure was well recognized and all involved were confident that with proper laboratory monitoring patient safety could be assured

When the first (predictable) cases of liver failure were reported, FDA determined that only 9% of physicians were following the rezulin label and obtaining LFT’s. Therefore the drug was withdrawn on the grounds that safety could not be maintained in the marketplace


Frequency of pharmaceutical risk management recommendations:

Clinical Issue Patients (N)

Triggering (%)

Need for LFT’s on Rezulin 155 13%

Need renal monitoring on Metformin 329 19%

Need for INR’s on Coumadin 153 7%

Need for LFT’s on Statins 931 10%

In other words, 87% of physicians in this sample were monitoring their Rezulin patients (not 9% as FDA thought) and those who were not monitoring frequently complied with a single reminder letter.


Proven Results

Sentinel systems are currently workable and deployable

Sentinel systems can play a direct role in pharmaceutical risk management

Sentinel systems suggest action that Physicians will accept and implement

The costs of sentinel systems are more than offset by savings in health care

Are Sentinel Systems merely a Dream?

25 Million Americans already say NO!– However, these systems were engineered only for the purpose of

patient safety and care improvement

The next phase is the RHIO –Regional Health Information Exchange

– First Gateways: 20 million lives this year– Indiana: 5+ million lives– New England: 5+ million lives

– RHIOs are being engineered primarily for transportability of health information, driven by health systems economy, with patient safety as a secondary opportunity and postmarket surveillance not even a major topic of conversation.


The RHIO environment

Draws together all known diagnoses, procedures, admissions, labs, and increasingly other findings under a common data umbrella.

Privacy and security issues have been legislated and ironed out.

Provides the ideal environment for post-market surveillance, in addition to patient safety

The problem is the business model to support RHIOs – right now they are grant funded


Business Case for RHIOS

Today’s case– 1 in 5 diagnostic tests is performed simply because the

results of previous tests are not available during the time frame of the medical decision

– 1 in 8 hospital admissions is triggered by events resulting from failure of information flow in the outpatient environment

Tomorrow’s case– New drugs will come to the market sooner– Drugs will be less likely to be withdrawn from the market

because of unexpected and unmanageable toxicities– Patients will be more likely to be offered critical, lifesaving

drugs


The future opportunity

Reallocate current resources spent on episodic reporting to supporting RHIO initiatives

Create a structure for earlier monitored drug launches in a RHIO environment with user fees paid by the sponsors– Instead of requesting a 10,000 person premarketing safety study,

the safety results from 100,000 patients can be obtained in a RHIO environment at far lower cost

Replace single product risk management programs with population based programs that work through and simultaneously support the evolving RHIO structure



Cost Effectiveness

Sentinel systems cost approximately $10 per person / year to implement

Cost represents < 0.5% of overall health care costs

Direct savings exceed costs at least 10-fold, not including the benefits to industry and FDA of safer drugs, maintained in the marketplace

Extrapolation of these implications to the nation suggest that a very modest level of IT investment (i.e. not universal EHR’s) could readily save the country in excess of $70 Billion/yr


Think about the potential for doing better, more real-world clinical studies at a much more affordable cost. For example, post-approval studies could be much cheaper and easier to do, using clinical protocols administered over the internet via electronic records, with patients selected and results recorded directly from electronic medical records. Low-cost clinical trials to be performed more quickly and easily in real-world medical settings. And we can use the signals we obtain from our better surveillance system to work with health care providers, funding agencies, and health care payers to target these studies more effectively.

Mark McClellan, MD, PhDTestimony to the

President’s Information TechnologyAdvisory Committee -- 2003

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Is FDA failing us Or are we failing FDA? Jonathan C. Javitt, M.D.,M.P.H Senior Fellow, Potomac...

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