Policy, Regulatory and Research

Stages of Drug Development:

1	IND	Animal tests
2	IND Review by FDA and local IRB	Animal tests
3	Phase 1	Healthy volunteers, tests safety
4	Phase 2	Sick volunteers, tests effectiveness
5	Phase 3	Larger scale, test effectiveness and adverse effects
6	Post-marketing	Review
7	NDA application
8	FDA Review and decision
9	FDA Review and decision
10	FDA decision

Expedited IRB Review:

• Minimal or no risk
• Involve data, documents, specimens etc that have been collected for non-research purposes.

IRB Exempt:

• Research in established or commonly accepted educational settings
• Use of educational tests where subjects cannot be IDed
• The use of texts and surveys if the subject is a public official under FOIA.
• Collecting or studying existing data that is redacted or available under FOIA.
• Federal research for public benefit or social programs
• Taste and food quality

IRB Requirements

• Each IRB needs 5 members.
• They must have at least 1 science and 1 non-science member
• Consideration is made race, gender, cultural background and sensitivity to the subject matter.
• Try to get an equal number of males and females, but it’s not a requirement.
• At least one IRB member must be non-affiliated with the intuition
• No IRB member may have a conflict of interest.

Common Rule – informed consent

• Additional protections for pregnant women, human fetuses, and neonates; additional protections for prisoners; and additional protections for children
• Children:
  • Children under 18 need to have their parents’ permission in order to participate in research. In addition, they must themselves be asked to agree (“assent”) to participate.
  • Situations may arise where a grandparent or other relative is raising the child and has physical custody but, may not be the child’s court-established legal guardian. Therefore, a copy of the court order naming her or him as the child’s legal guardian with the ability to consent for the child’s medical care must be provided to the study team and filed with the consent form.
  • In determining whether children are capable of assenting, the IRB must take into account the ages, maturity, and psychological state of the children involved. This judgment may be made for all children to be involved in research under a particular protocol, or for each child, as the IRB deems appropriate. If the IRB determines that the capability of some or all of the children is so limited that they cannot reasonably be consulted or that the intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research, the assent of the children is not a necessary condition for proceeding with the research. Usually, the age of assent is 7, but some institutions may have higher or lower age limits.
• Permitted research on prisoners:
  • A study on criminal behavior that has minimal risk and inconvenience
  • A study of prisons as an institution or prisoners as incarcerated people that have minimal risk and inconvenience
  • Research on topics that particularly affect prisoners as a class
  • Research on practices, innovative and accepted, that have the intent and reasonable probability of improving the health or well-being of the subject.
• Pregnant Women:
  •  For research that holds out the prospect of direct benefit to the pregnant woman, the prospect of direct benefit both to the pregnant woman and fetus, or no prospect of benefit for the woman nor the fetus when risk to the fetus is not greater than minimal and the purpose of the research is to provide important biomedical knowledge that cannot be obtained by other means, consent of the pregnant woman must be obtained
  • If research has the prospect of direct benefit solely to the fetus then the consent of the pregnant woman and father is obtained. The father’s consent need not be obtained if he is unavailable, incompetent, or the pregnancy resulted from rape or incest.

Medication Error Definitions:

• Mild: enhanced monitoring, no harm
• Moderate: active treatment required, enhanced monitoring, but no lasting harm
• Severe: patient harm that requires enhanced treatment and increased patient stay

FDA’s Adverse Event Reporting System (FAERS):

• FAERS is a database that contains adverse event reports, medication error reports and product quality complaints resulting in adverse events that were submitted to FDA. The database is designed to support the FDA’s post-marketing safety surveillance program for drug and therapeutic biologic products.
• Healthcare professionals, consumers, and manufacturers submit reports to FAERS.
• FDA receives voluntary reports directly from healthcare professionals (such as physicians, pharmacists, nurses and others) and consumers (such as patients, family members, lawyers and others).
• Healthcare professionals and consumers may also report to the products’ manufacturers. If a manufacturer receives a report from a healthcare professional or consumer, it is required to send the report to FDA as specified by regulations.
• Reports are submitted via MedWatch (an FDA website).
  • Facilities, distributors, importers, applicants, and manufacturers submit a different, mandatory report then consumers and healthcare professionals.

This section is tricky.  I recommend knowing a few laws and what they do.

• Food, Drug and Cosmetic Act (1938) – Give authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of food, drugs, medical devices, and cosmetics. Covers orphan drugs.  The introduction of this act was influenced by the death of more than 100 patients due to a sulfanilamide medication.
  • FYI: Medical devices are classed as I-III – I – least risk, II – moderate risk, III – highest risk.  III  requires FDA approval.
• Health Insurance Portability and Accountability Act (1996) – Created primarily to modernize the flow of healthcare information, stipulate how Personally Identifiable Information maintained by the healthcare and healthcare insurance industries should be protected from fraud and theft, and address limitations on healthcare insurance coverage.
• FDA Modernization Act (1997) – This act amended the Federal Food, Drug, and Cosmetic Act.  This streamlined research on drugs and devices and established clincaltrials.gov.  The act reauthorized, for five more years, the Prescription Drug User Fee Act of 1992 (PDUFA). The purpose of this was to enable the FDA to reduce the average time required for a drug review from 30 months to 15 months.  The law abolishes the long-standing prohibition of broadcasting by manufacturers of information about unapproved uses of drugs and medical devices.
• FDA Safety and Innovation Act (2012) – This act gives the United States Food and Drug Administration (FDA) the authority to collect user fees from the medical industry to fund reviews of innovator drugs, medical devices, generic drugs and biosimilar biologics. It also creates the breakthrough therapy designation program and extends the priority review voucher program to make eligible rare pediatric diseases.
• Best Pharmaceuticals for Children Act and Pediatric Research Equity Act (2002) – Companion legislation acts that together have resulted in a significant increase in new knowledge about the safe and effective use of medicines leading to a significant increase in the number of drugs that have pediatric labeling.
• Affordable Care Act (2010) – One thing it did that is applicable to clinical pharmacists was to establish biosimilar guidelines.
• FDA Amendments Act (2007) – This law reviewed, expanded, and reaffirmed several existing pieces of legislation regulating the FDA. These changes allow the FDA to perform more comprehensive reviews of potential new drugs and devices.  The FDAAA extended the authority to levy fees to companies applying for approval of drugs, expanded clinical trial guidelines for pediatric drugs, and created the priority review voucher program.  An important thing it did was to establish REMS programs.
  • REMs programs involve training for the prescriber, lab tests and a registry.
  • You might check out the drugs with REMs programs on the FDA website.
• Institute For Safe Medication Practices (ISMP) – This isn’t a regulation, but there isn’t a good place to add it.  The ISMP is a non-profit organization educating the healthcare community and consumers about safe medication practices.  They publish safety alerts  on emerging drug risks including QuarterWatch and unsafe abbreviation lists.

Random things they ask:

• Names of tests for disease states (ie: Montreal Cognitive Assessment, for example)
• All names are generic
• Know drugs with REMS programs, NTIs and Black box warnings well.