Pharmaceutical Harm is more than just adverse reactions; it is a system-wide problem. There is a lack of transparency and questionable protocol that add to patient harm. Below are some components of the flawed system.
The FDA’s Center for Drug Evaluation and Research (CDER) breaks down the approval process into the following phases:
1. Preclinical: After a drug company discovers a new compound, the FDA-approval process is started. The drug must first be tested on animals to determine safety, effectiveness, and toxicity levels of the drug. After compiling initial data, the company then submits an Investigational New Drug (IND) to the FDA. The IND includes results from the animal testing and a plan for human testing. It is at this point in the process that the FDA makes a decision on the risk vs. benefit.
2. Clinical Study: The drug company conducts testing on humans and clinical trials consist of 3 phases.
a.) Phase 1- To discover the drug’s most frequent side effects.
b.) Phase 2- Researchers gather preliminary data on how the drug works in people with certain disease or condition. They compare the drug against a placebo.
c.) Phase 3: Researchers test the safety and effectiveness in a larger number of people on different doses and varying combinations of other drugs.
3. New Drug Application (NDA) review: Once clinical trials end, the drug company submits a New Drug Application. The FDA has 60 days to review the NDA before filing it. Once that happens, it reviews the research submitted by the drug company for safety and effectiveness and it reviews the proposed label. Lastly, the FDA inspects the facility where the drug is manufactured. It is at this point that the FDA either approves the drug or rejects it.
Prescription Drug User Fee Act (PDUFA)
During the New Drug Application review process, the drug companies may apply for Accelerated Approval, also known as Fast-tracking. This is allowed under the Prescription Drug User Fee Act (PDUFA). PDUFA was a law passed by the United States Congress in 1992 which allowed the FDA to collect fees from the drug manufacturers to fund the new drug approval process. It is passed every five years, and Congress can add things to it. PDUFA allows for pharmaceutical companies to pay fees in order to fast-track a medication through the approval process. It is likened to “approve now and ask questions later”. The fast-tracking takes into account what are called “surrogate endpoints” to determine effectiveness.
A surrogate endpoint is an indicator such as medical testing (blood testing, scans) used to tell if a treatment works but does not guarantee its effectiveness. Using the example of a cancer drug, if a drug reduces a tumor, the FDA considers it effective even if there is no clinical trial data showing that it prolongs your life.
The FDA’s funding comes from taxpayers, but close to 50% of drug approval funding comes from the drug companies themselves- the very industry it should be regulating. PDUFA was passed to provide a budget to hire more scientists to review the extra load of drug approvals. This brings up many red flags for consumer groups and patient advocates in that there is a greater chance of adverse events post-approval when a drug is fast-tracked. Adverse reactions are not discovered in a timely manner and this puts patients at risk. Faster does not always equal better.
Patient Safety Concerns About Pre-Approval Process
- Clinical trials can be too small to give proper estimation of adverse events.
- Clinical trials can be too short and do not account for dangerous adverse events which occur several years later.
- Some clinical trials can use healthy clinical trial participants and may not include a sicker population who would benefit from the drug.
- Physicians may prescribe a drug off-label; uses not studied or approved by the FDA.
Patient Safety Concerns About Post-approval Process
- Adverse events are not always reported; they are voluntary.
- While the FDA can request a post-market study to follow up on safety concerns, the drug makers do not have to do them.
- Drug makers do not always publish unfavorable clinical trials.
- There is no system in place to analyze large databases of patients for adverse events.
An investigation into the Food and Drug Administration’s (FDA) adverse event reporting system reveals serious flaws that may delay the dissemination of timely information about risks and dangers associated with some prescription medications. Unless drastic changes to the system are implemented, patients may continue to unknowingly put themselves at risk when taking medications prescribed by their physicians that they assume to be safe.
The investigation revealed that reports over a one year period between 2013 and 2014 were either sent directly to the FDA through the agency’s MedWatch program or to drug manufacturers that in turn sent the information to the FDA. The report concluded that events reported through drug manufacturers were much less likely to contain complete information.
In addition, less than 10% of adverse reactions are even reported to MedWatch. Many patients don’t know they could report adverse events or they don’t connect the side effects to the medication they are prescribed. The reporting system largely relies on patient reporting; doctors are less likely to report adverse events and it is not mandatory that they do so.
Many drugs that are suspected to have serious side effects cannot be accurately monitored without a consistent and accurate reporting system. The only way to change that is to completely overhaul the system.
Report Your Adverse Event to the FDA
If you experience any adverse reaction or side effect, it is important to report your adverse reactions to the FDA’s MedWatch system.
Go to the FDA website https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?action=reporting.home.
Choose Begin Report As a Consumer/Patient.
Report by phone: 1-800-FDA-1088
Report by fax or postal mail: Download and print Form 3500B:
Mail the form to:
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
Or fax to:
Direct-to-consumer (DTC) Ads
Patients and doctors learn about medications from TV ads. The only two countries in the world that allow pharmaceuticals to be advertised on television are the United States and New Zealand. Direct-to-consumer ads are banned in all other countries.
When you look at the dynamics behind the drug ads, it is easy to see why many countries ban them.
First and foremost, these ads are misleading.
Let’s break them down:
The FDA requires manufacturers to list the side effects but the visuals conflict with the verbal message. The commercial shows a happy family enjoying activities while the side effects are listed. The FDA has the authority to regulate these ads, but do not have the resources. The warnings in the ads reflect the warning labels. If there is not a Black Box warning on certain side effects, it’s not required in the commercial. The pharmaceutical industry negotiates with the FDA about what is listed and what is not, and drug companies provides the information.
Generic medications are copies of brand name drugs after the patent expires for the brand name. At least 80% of all medications dispensed are generic. Once a patent expires on a brand name medication, that manufacturer no longer has exclusive rights to sell it. Other manufacturers can apply to the FDA to make a generic version of the brand name and they can sell it at a cheaper price because the brand name company had the burden of paying for research, development, and promotion of the drug. The FDA requires that generic drugs be as safe and effective as brand-name drugs.
But thanks to a federal regulation and a U.S. Supreme Court ruling (Pliva v. Mensing), in exchange for the lower price, you may be giving away your right to sue if the label didn’t warn you about potential adverse reactions and harm. Because the drug is a generic, the manufacturer could be shielded from liability for an inadequate warning on the label. A generic drug manufacturer cannot change warning labels on medications unless the brand name manufacturer act first.
In an effort to address this issue, the FDA proposed a rule that would allow manufacturers of generic drugs to update label information more quickly once new health and safety information becomes available.
I had the honor of testifying at the FDA hearing held on March 27, 2015.
A decision on the proposed rule has been delayed three times as of this writing.
Video of the hearing can be found here.
Part 1: https://collaboration.fda.gov/p4vtitcjbcb/?launcher=false&fcsContent=true&pbMode=normal
Part 2: https://collaboration.fda.gov/p62plg4hlc4/?launcher=false&fcsContent=true&pbMode=normal
Part 3: https://collaboration.fda.gov/p1butpdfuap/?launcher=false&fcsContent=true&pbMode=normal
Part 4:I am the third speaker- https://collaboration.fda.gov/p16w66yyjfa/?launcher=false&fcsContent=true&pbMode=normal
12 Questions to Ask If Your Doctor Brings Up a New Medication
Every patient has the right to information regarding their health and well-being in order to make informed decisions. Finding the balance between lack of transparency and wading through vast amounts of information often comes down to asking the right questions.
The following are 12 questions to ask your doctor when the subject of new medication is introduced. It comes from years of personal experience as well as professional experience being a patient safety advocate. I will also explain why asking these questions are important. Having as much information as possible allows you to paint a complete picture about what you feel is best for you.
Questions to Ask If Your Doctor Brings Up a New Medication
Do you mind if I record this conversation with my phone so I can have it to refer to when I do my research?
Why is this important?: Recording a conversation means that you won’t have to rely on your memory to recall information during your visit. It also increases the likelihood that there will be more transparency about the risk vs benefit ratio of a new medication.
For what condition is this medication prescribed?
Why is this important?: Drugs often have more than one use. Understanding why a drug is being prescribed increases your knowledge of the medication and the condition for which is it prescribed.
Is it being prescribed off-label? If so, is there another medication specific to my condition?
Why is this important?: Prescription drugs are often prescribed for uses other than what the FDA has approved. This is legal, and in fact common. The FDA regulates the approval of a drug, not how it is prescribed. At least one in five outpatient prescriptions are prescribed off label and doctors are not necessarily required to inform a patient that a medication is being prescribed off label. Off label use is not necessarily a bad thing but it is important that a patient is fully aware of what they are taking and for what condition.
What are the risks associated with this medication and do the benefits outweigh those risks?
Why is this important?: Adverse reactions (ADRs) or adverse events (ADEs) can have a major impact on the health and well-being of patients. It’s something that I found out the hard way. I was never informed of the adverse reactions associated with Levaquin, many of which are permanent. Sometimes, unfortunately, the treatment can be worse than the illness for which it is prescribed. FDA approved does not always mean that a product is safe. Having a complete picture of the risk vs. benefit helps patients make an informed decision about their care and appropriate use of the medication.
Is this a new medication? If so, is there an older, more tried-and-true medication available?
Why is this important?: Newer doesn’t always mean better. There is no regulation requiring new medications to be better than older medications before they are approved by the FDA. The FDA approves approximately 20-25 new and unique medications annually. Of those, only four or five represent major advances for conditions with no decent treatment choices. The remaining new medications offer only marginal improvements or are combinations of what is already on the market, which are called “me too” drugs.
Is this medication necessary to my well being or are there alternative treatments I can try first?
Why is this important?: There may be other medications to consider for your condition. Some medications may be more effective but carry greater risks. There is also cost to consider. In some cases, medication may not be needed at all and other treatments may be available.
Will this medication interact with my other medications and/or other health conditions?
Why is this important?: Drug interactions may make your medication less effective, cause unexpected side effects, or increase the action of another drug. Medications can react with other medications, food, or beverage.
What are the Black Box warnings for this medication and where can I report adverse events?
Why is this important?: Black Box warnings are the strictest warning put in the labeling of prescription drugs by the FDA when there is reasonable evidence of association of a serious hazard with the drug, which can be life-threatening. Asking about Black Box warnings can help to protect your health and life. If you do experience an adverse reaction, it is important to report it to the FDA’s MedWatch, which can be found here.
What happens if I do not take this medication?
Why is this important?: You know what is best for you. You may decide that a medication has too many side effects, costs too much money, or you may think you might get better with alternative treatment. Asking what happens if you do not take a certain medication allows you to make an informed decision about what is best for you.
What is the cost of this medication and will insurance cover it?
Why is this important?: Many patients may face high out of pocket costs for prescription drugs each month, especially for those with chronic or multiple conditions. Even insured patients feel the burden. When the cost is too high, a patient may stop taking the medication, and this could be detrimental to the patient. Understanding the cost of prescription medications and whether it is covered by insurance can help prevent complications from stopping a medication cold.
Do you have any written information about this medication?
Why is this important?: Patients need accurate information to help them use their medications safely and effectively. Having written information to refer to helps patients fully understand everything they need to know.
Have you ever received any gifts or financial benefits from the company that makes this medicine?
Why is this important?: Doctors are not required to disclose payments they receive from pharmaceutical companies to prescribe their drugs. Patients want to know that the medication being prescribed is because it is in their best interest, not because doctors receive money to do so. Understanding these ties is important. Many brand name drugs are expensive and carry dangerous adverse reactions. As a patient and consumer, you have the right to know whether your doctor has close pharmaceutical ties. You can find out here.