Medical Innovation Impact Index Alerts

Sun 20 Nov2016

MI³™ Alert: Tiered Orders of FDA Approval Based on Evidence of Effectiveness

Nov 20 2016|Medical Innovation Impact Index Alerts|

In 1962, Congress passed the Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act), which authorized the FDA to require drug companies to conduct and submit tests determining safety and efficacy prior to approval for marketing. In addition, the FDA now had to preclear all human trials. This occurred in response to thalidomide-induced birth defects that were observed in the drug’s use in 46 countries; interestingly, the drug was not approved for use in the US as the FDA was investigating neurological toxicities during its review of the approval application submitted in 1960. Still, the horror of seeing truncated limbs resembling flippers in newborns resulted in the passage of the amendments, which significantly expanded the power of the FDA as well as its size – staff increased from one thousand members in 1951 to nearly sixty-five hundred two decades later.

The goal of the effectiveness standard was to make certain that “snake oil,” that is, a drug with no biological activity in a disease, was not entered into the medical armamentarium. Regrettably, over the years, the FDA has amassed even greater power and authority as it has sought to redefine effectiveness to mean clinical utility, a highly personal measure best determined by doctors and patients. In many cases, drug activity (for example, shrinkage of tumors) is no longer good enough to satisfy effectiveness requirements, rather, long-term health outcomes, including survival are the preferred measures of effectiveness mandated by the FDA. Is this good for medical innovation?

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Wed 16 Nov2016

MI³™ Alert: FDA Advisory Committee meetings (AdComm)

Nov 16 2016|Medical Innovation Impact Index Alerts|

FDA Advisory Committee meetings (AdComm), also known as Panel meeting (Panels), are major public events in the drug development cycle that are convened by the FDA, according to 21 USC 355: New drugs(n) Scientific advisory Panels, governing
drugs and biologics – “For the purpose of providing expert scientific advice and recommendations to the Secretary regarding a clinical investigation of a drug or the approval for marketing of a drug under section 505 or section 351 of the Public Health Service Act, the Secretary shall establish Panels of experts or use Panels of experts.” It further states, “after a scientific
advisory Panel makes recommendations on any matter under its review, the Food and Drug Administration official responsible for the matter shall review the conclusions and recommendations of the Panel, and notify the affected persons.”

The device regulations (21 USC 360e(c)(3): Premarket approval) state, “Upon receipt of an application…the Secretary shall refer such application to the appropriate Panel under section 360c of this title for study and for submission of a report and recommendation respecting approval of the application, together with all underlying data and the reasons or basis for the
recommendation.” It further states, “the Secretary, after considering the report and recommendation submitted under paragraph…”

The law was clearly written to obtain the approval recommendations of outside clinical experts. It would not be appropriate at other Panel meetings (for example, those convened to discuss scientific issues that affect multiple products or a class of products, or to consider study design issues affecting drugs in development but not yet submitted for approval), of course, to require votes on approval recommendations. However, AdComms at which the approval applications for new products are being considered were intended to include a vote on the approval recommendation from the Panel.

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Tue 9 Aug2016

MI³™ Alert: Compounding Pharmacies

Aug 9 2016|Medical Innovation Impact Index Alerts|

According to the FDA, the term “compounding includes the combining, admixing, mixing, diluting, pooling, reconstituting, or otherwise altering of a drug or bulk drug substance to create a drug” (21 USC 353b – The Compounding Quality Act or Drug Quality and Security Act of 2013). Compounded drug products serve an important role for patients whose clinical needs cannot be met by an FDA-approved drug product such as for a patient who has an allergy and needs a medication to be made without a certain dye (or preservative or flavoring) contained in an FDA-approved drug, or an elderly patient or a child who cannot swallow a pill and needs a medicine in a liquid form that is not available in an approved product. Drugs for identified individual patients can be compounded by licensed pharmacists in state licensed pharmacies and federal facilities and by licensed physicians operating under Section 503A of the FD&C Act. Sterile drug products can also be compounded by outsourcing facilities for distribution to health care practitioners across state lines without receiving prescriptions under Section 503B of the FD&C Act. One to three percent of prescriptions filled in the U.S. by community pharmacies are estimated to be for compounded medications; the percentage of compounded drugs used in hospitals, especially those for intravenous therapy, is significantly greater. Many have called for the FDA to do more in light of several instances of significant quality concerns, especially from “industrial compounders” of sterile drugs. However, the FDA’s hands have been tied by Congress and the courts, leaving the primary responsibility to the states, which have incomplete and inconsistent policies and enforcement practices. So, how can appropriate regulation and oversight of pharmaceutical compounding be performed to ensure patient safety without severely limiting the supply of customized products and intravenous therapies that are not available from drug companies?

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Tue 1 Dec2015

MI³™ Alert: Congressional Oversight of the FDA

Dec 1 2015|Medical Innovation Impact Index Alerts|

Congress certainly expends great effort passing laws that have the goal of enhancing medical innovation, for example PDUFA (Prescription Drug User Fee Act) and MDUFA (Medical Device User Fee Act) reauthorization. The question is whether better Congressional oversight would result in a greater number of more profound medical innovations reaching patients more quickly.

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Fri 30 Oct2015

MI³™ Alert: Medicare Negotiating Drug Prices

Oct 30 2015|Medical Innovation Impact Index Alerts|

Should Medicare be empowered to negotiate directly with pharmaceutical companies as one large buyer, instead of through many individual plans? Should Medicare be empowered to force the types of discounts that Medicaid and the VA receive? What are the implications for medical innovation?

Download the full MI³™ Alert [PDF]

Wed 16 Sep2015

MI³™ Alert: Off-Label Drug Use and Promotion

Sep 16 2015|Medical Innovation Impact Index Alerts|

This MI³ Alert scores off-label drug use and promotion. Off-label drug use entails the prescribing of an approved drug for use in a manner that is not specified in the FDA’s approved label, or package insert. Off-label promotion is defined as the intention (encouragement of physicians and advertising) of a drug manufacturer to have its drug used in a manner that is not explicitly supported in the FDA-approved labeling. Off-label use is legal, but off-label promotion is not. This MI³ Alert highlights ramifications of these conflicting policies.

Download the full MI³™ Alert [PDF]

The Medical Innovation Impact Index (MI3™) is a scoring system for important new proposed regulations (laws, rules, guidance documents), as well as for existing policies. It will mirror the “Environmental Impact” assessment that all new projects must include by Federal Law. The goal is to analyze the consequences (unintended and intended) of new and existing policies (FDA, SEC, patent law, healthcare delivery).

The Medical Innovation Impact Index (MI3) is a succinct, real-world based analysis and scoring system. On the positive side, the purported benefits and potential positive impacts on medical innovation are listed and scored zero to 5, based on the likelihood of achieving these objectives. On the negative side, the unintended consequences and potential negative impacts on medical innovation are listed and scored 0 to -5, based on the likelihood of these untoward effects happening. A final composite score (ranging from -10 to +10) is calculated and a recommendation is offered.

  1. Purports to do – likelihood of achieving objectives (0 to +5)
  2. Potential Positive Impact on Innovation – likelihood of achieving (0 to +5)
  3. Unintended Consequences – likelihood of consequences occurring (0 to -5)
  4. Potential Negative Impact on Innovation  – likelihood of negative impact (0 to -5)

Regular MI3 Alerts highlighting existing as well as proposed new laws, rules, guidance documents, and policies that have an impact on medical innovation will be issued. The goal is to advance medical innovation by identifying policies that enable and hinder the development of meaningful patient-centered innovations.

The analyses are driven from “in-the-trenches” experiences of our staff and advisors who are in the front lines of the development and dissemination of medical innovations to patients. This unprecedented approach, based on real-world and practical, experiential considerations is sorely needed and in sharp contrast to the theoretical and detached evaluations performed by the government agencies (FDA, CMS, SEC, etc.). Most important, it is concerned solely with the impact on medical innovation.

While a great deal has been written about the negative effects of regulation on innovation in all sectors, and surveys have been conducted regarding the stifling effects of regulation on medical innovation, there is no independent analysis and scoring of policies, rules, guidance documents, and proposals relative to their likely impact on medical innovation.

During the rule-making process for regulations that are economically significant (having a likely impact of at least $100MM), a Regulatory Impact Analysis (“RIA”) is required, which includes evaluations stipulated by Executive Orders 12866 and 13563. But, no such analysis exists to evaluate rules solely relative to their impact on the advancement of medical innovation. Moreover, the RIA is not mandated for guidance documents, which are the methods by which the FDA publishes detailed interpretations of its rules, truly where the rubber meets the road.

Medical innovation is too important to be neglected or left to regulators to weigh. Our understanding of fundamental biology is progressing at a lightning pace and providing tremendous medical discoveries and insights. Patients are demanding more immediate access to cutting edge therapies as evidenced by the Right to Try Law movement. Investors have increased the pace at which they have been allocating capital to the sector broadly. However, over-regulation and the inconsistent application of laws and rules continues to handicap the timely development and approval of new medicines and devices.

Nothing transformative is being done to address the problem principally because it is hard to do. For government agencies like the FDA, it is easier to propose rules and guidance documents with great sounding titles in order to deflect criticism of inadequate performance. For elected officials who need to show activity within their term periods, it is easier to mollify constituents with proposals and laws that give some acknowledgement of their pain, but accomplish little. For drug developers, it is easier to target diseases for which the greatest regulatory incentives exist because this provides the quickest way to maximize shareholder value.

Seemingly, no one wants to perform the hard work of analyzing the implications of the system of laws, rules, guidance documents, policies, and resultant modus operandi relative to their collective impact on medical innovation.

We do. And, it is critically important to patients and society that we perform this difficult work.