Tag: Off-label

How to ensure the drugs you take are safe and effective
Drugs recently approved by the Food and Drug Administration–within the last ten years–may turn out not to be safe or effective. How can this be? And, how can you ensure the drugs you take are safe and effective?

To be clear, the FDA only approves drugs that it finds to be safe and effective. But, it bases its approval on limited data. So, what might appear to be safe and effective at the drug approval stage, may turn out not to be. One in seven older adults experience harmful drug side effects.

To get a drug approved, pharmaceutical companies must conduct clinical trials or lab tests that show the drug is safe and works better than a placebo, essentially a sugar pill or nothing. But, clinical trials are usually performed on a small cohort of people, a tiny fraction of the number of people who will end up taking the drug. Often the people in the clinical trials are not elderly or children or otherwise like the people who are prescribed the drug. As a result, in the real world, outside of the clinical trials setting, the drug may be ineffective or, worse still, dangerous for some people who take it. Drug safety is a big issue.

Sometimes, a drug’s potentially dangerous side effects may only become evident after six months or a year of a person taking it. But, a clinical trial may last for only six months. And, about 10 percent of the time, a drug may be prescribed for off-label use. When prescribed off-label, for a different condition from which it was tested, people may experience dangerous side effects. Keep in mind, as well, that peer-reviewed papers showing the value of the drug for a particular condition, may be biased. Too often the papers’ authors have financial ties to the drug industry.

Unfortunately, the FDA does not do the job it needs to do monitoring drugs after they are approved and publicly reporting their side effects. Indeed, because it is very hard to prove that people’s side effects stem from a particular drug, drugs with dangerous side effects may not be pulled from the market for many years. Even warnings about these side effects may not be published.

What can you do?
1. Choose your doctors carefully. Make sure that your doctors listen to you and take the time to know you.
2. At each doctor’s visit, question whether you still need to be taking the prescription drugs your doctor has prescribed or whether it is possible to stop taking one or more of them.
3. Check to see whether your doctor is taking money from drug companies on Dollars for Docs. If so, consider talking to your doctor about that in connection with the drugs your doctor has prescribed for you.
4. If there’s a generic substitute for the drugs you take or a lower-cost alternative, ask your about switching to that drug.
5. If a drug you are taking was recently approved by the FDA, ask about side effects and whether there is an older drug you could be taking instead. With an older drug, you have a better sense of the drug’s safety and usually pay less for it.
Ironically, the FDA does not allow people to import drugs for personal use for “safety” reasons. That said, Kaiser Health News reports that 19 million Americans import drugs from abroad every year. No one has ever reported a safety issue from prescribed drugs bought from a verified pharmacy abroad. Indeed, by some counts 70 percent of the drugs we take in the US were manufactured abroad.

Here’s more from Just Care:
October 16, 2018
Should generic drug labels include off-label uses?
A new bipartisan Senate bill would allow generic drug labels to include off-label uses, Nicholas Florko reports for StatNews. With an FDA finding of sufficient evidence, the bill empowers generic drugmakers to market drugs for particular conditions even though those drugs have not been scientifically proven to treat those particular conditions. It is hard to believe this helps anyone other than the drugmakers.

Senators Orrin Hatch (R-UT) and Michael Bennett (D-CO) introduced the legislation that would lift marketing restrictions on generic pharmaceutical companies. Today, generic drug companies need approval from the FDA to change a drug’s label. Only then can they market a drug as a treatment for a new condition or a new drug dose. And, that takes time and money.

Generic drug companies also do not have the right to set in place the process for marketing a drug for off-label use–a different treatment or a different dosage from what was originally intended. Brand-name drug companies only have that right. But, if the brand-name product is pulled from the market, the brand-name drug company that had promoted the drug for a particular use has no incentive to promote the drug for another use. So, the drug labels rarely change.

The Hatch-Bennett bill would give the FDA authority to review data on generic drugs for off-label use when there is no brand-name competitor. If the FDA finds that there is enough evidence for it to be sold for those uses, the FDA can require a label change. But, the bill is silent as to what evidence would constitute sufficient evidence to require a label change on the generic drug.

This bill appears to give a lot of power to the FDA and the generic drug makers without adequately protecting individuals. No clinical trials showing the clinical benefits of the off-label use of the drug are required to determine safety issues. And, doctors can already prescribe drugs for whatever use they please. A label change is not required for doctors to prescribe a drug for off-label use.

The label change simply expands the drug companies’ ability to market a drug for a new use. Who is really benefiting here?

Here’s more from Just Care:
October 2, 2018
Pharma fingerprints all over Trump drug price executive order
Across the political spectrum, Americans support reining in prescription drug prices—Democrats, Independents and Republicans alike. But, despite claims to the contrary, President Donald Trump has no intention of reining in drug prices. A draft Trump Executive Order on drug prices obtained by the New York Times has Pharma’s fingerprints all over it and is designed to drive up drug prices further. It’s all about strengthening the power of drug companies to set prices around the world.

Pharma wants greater power to charge people outside the U.S. more, as reflected in the draft Executive Order. But, higher prices outside the U.S. likely means higher prices around the world. Pharma is making no promises to reduce drug prices in the U.S.

Pharma also wants to loosen U.S. regulations so that drugs get to market faster at less cost to the drug industry. But, that policy–also in the draft Executive Order–would jeopardize patient safety further, not promote lower drug prices.

Pharma’s support of value-based pricing, another piece of Trump’s draft Executive Order, sounds good in theory. But, it is another way for Pharma to try to justify high drug prices. Only if somehow it can be proved that the particular drug didn’t work would the price come down. And, Pharma is not proposing a full refund for drugs that don’t work, as tends to be the case with other products that do not deliver value. Moreover, how much time and money would it take to prove lack of efficacy or patient safety?

Pharma also wants to be able to charge more for drugs to hospitals treating low-income patients under the 340B program.

The draft Executive Order does not suggest discounting drugs for people with Medicare, nor does it recommend reducing brand-name drug prices.

And, a proposal in the draft Executive Order to give more tax breaks to companies manufacturing generic drugs would mean more money to Pharma with no guarantees of lower generic drug prices. Yet, another proposal to permit dissemination of off-label information to insurers and PBMs pre-FDA approval also would undermine patient safety.

Not surprisingly, the New York Times reports that many of the people involved in drafting the Executive Order have longstanding ties to the drug industry.

Senator Franken along with several other Senate Democrats have a bill in Congress to rein in drug prices–the Improving Access to Affordable Prescription Drugs Act. Congresswoman Jan Schakowsky has introduced a complementary bill in the House.

If you believe that we need policies to rein in drug prices not give Pharma more power to drive prices up, please sign this petition.

Here’s more from Just Care:
June 27, 2017
Bitter pills: Once popular drugs pulled from the market

Nearly 5 billion dollars.

That’s how much pharmaceutical company Merck paid to people and families who claimed the painkiller Vioxx harmed them or their loved ones. In one of the largest civil lawsuit settlements in recent history, the Vioxx manufacturer in 2007 agreed to pay $4.85 billion to people involved in the 27,000 outstanding Vioxx lawsuits against Merck. Those cases claimed that Vioxx was linked to stroke, heart attack or premature death. But while the company agreed to settle, it never admitted the drug was at fault.

Many drugs that come on the market with promise are advertised to the hilt and taken by thousands or millions of people around the world — and then either quietly (or with a big splash, as with Vioxx) disappear. Why? Here are four reasons:

1. Clinical trials aren’t as big as you think, explains drug safety expert Glen Schumock, PharmD, the head of the department of pharmacy systems, outcomes and policy at the College of Pharmacy at the University of Illinois, Chicago. Some may enroll as few as 1,000 people, and while all side effects are noted, some are uncommon. “Say there’s an adverse effect in 10 out of 100,000 people, but if you only have 6,000 people in your trial, you might not see that side effect because the frequency is so rare,” says Schumock. Consider, though, when that drug is given to 1,000,000 people — that means 10,000 people will have that “rare” side effect. (See our blog, “Do Rare Side Effects Happen?”)

2.”Real world” use of a drug differs, sometimes dramatically, from what goes on in a clinical trial. People selected to take part in a trial “typically have to meet some kind of criteria that is designed to give the drug the best chance to work,” says Schumock. Trial subjects may not be as sick as the average patient, are not taking other medications, and don’t have other diseases. Such participants are also highly monitored, typically seeing a medical professional every couple of weeks. Clinical trials are controlled environments. The real world, well, isn’t.

3. Time plays a role. Once a medication is approved by the FDA, patients and physicians may discover negative food or other drug interactions that didn’t occur during the trial’s timeline.

4. Off-label prescribing may bring up unexpected issues. A drug may be approved for one condition or population, but physicians are free to prescribe it for other uses or people, including children or the elderly, says Schumock. This can be problematic: children can be more sensitive to a drug’s side effects; the elderly, who may be more likely to have kidney function problems, might be exposed to more toxicity because the drug leaves the body at a slower rate.

All this helps explain why some drugs might get pulled from the market — either thanks to legal or regulatory pressure, or voluntarily on the part of the manufacturer — but you may not always hear that a drug is no more.

This post is excerpted from Medshadow. To read more about drugs that have been pulled from the market, click here.

April 7, 2016
Side effects of drugs prescribed off-label often serious

The Supreme Court is about to consider whether drug companies should be allowed to promote their drugs for off-label use as a matter of free speech. A new study in JAMA of drugs prescribed off-label suggests that it would be a grave mistake. The researchers find serious risks from off-label use of drugs in many instances.

The research suggests that doctors who prescribe drugs off-label do so with greater care and monitor the effects on their patients. The researchers found that only 20 percent of the time that off-label drugs were prescribed was there strong evidence to support the prescription.

Data reveals that doctors often do not understand the indications for which the FDA has approved a drug’s use. So, patients should ask their doctors about these indications before opting to take a drug prescribed for off-label use. At the very least there should be strong evidence of the drug’s efficacy for its prescribed use.

To undertake the study, the researchers looked at electronic data for more than 45,000 Canadian patients over five years, including drugs prescribed, the reason the drug was taken and treatment outcomes—all of which is not available for patients in the United States.

Of the patients studied, 7.6 percent had bad side effects. Side effects were far greater–44 percent higher–for patients taking drugs off-label than for patients taking drugs for their approved use. The researchers did not find a difference in side effects between drugs used off-label and on-label when there was strong scientific evidence to support the off-label use.

What’s clear from the study is that we need to know a lot more about prescription drug use in the United States, both on-label off-label. We currently do not capture the reasons for which drugs are being prescribed and the outcomes for patients using the drugs. Today, it is conservatively estimated that 11.8 percent of drugs prescribed are for off-label use.

The FDA approves drugs only for particular use at a particular dosage, often based on clinical tests, checking for safety and efficacy. Sometimes, these approvals are based on laboratory evidence, where the data is less compelling and the safety and efficacy of the drugs less clear. Either way, the FDA dedicates few resources to monitoring drugs post approval. Although drug companies generally are not allowed to market them for off-label use, doctors may prescribe drugs for any reason they choose.

December 1, 2015