FDA Approval of Novel Therapeutic Agents

Many patients and physicians assume that the safety and effectiveness of newly approved drugs is well understood by the federal Food and Drug Administration (FDA). The article describes a study of the clinical trial evidence supporting FDA drug approvals, and the authors conclude that the quality of that clinical trial evidence varies widely. The team evaluated the strength of clinical trial evidence supporting FDA approval decisions for new drugs by characterizing key features of efficacy trials, such as trial size, design duration, and end points. FDA approved 188 novel therapeutic agents for 206 indications on the basis of 448 pivotal efficacy trials and that the quality of the clinical trial evidence supporting approval of these drugs varies widely across indications.

Most drugs were approved based on two efficacy trials, but for 74 indications (36.8%), drugs were approved based on only one efficacy trial. Additionally, for 91 indications (45.3%), drugs were approved based solely on trials using surrogate endpoints as their primary outcome. There was also significant reliance on surrogate endpoints, defined as “any endpoint using a biomarker expected to predict clinical benefit.” Trials using surrogate endpoints as their primary outcome formed the exclusive basis of approval for 91 indications (45%) among the study sample. The team also found that only 40% of drug approvals involved a clinical trial that compared a new drug to existing treatment offerings. This is an important step for determining whether the new drug is a better option than existing, older drugs.  Survey data shows that patients expect drugs approved by the FDA to be both safe and effective.

These results are unsurprising because the FDCA (Federal Food, Drug, and Cosmetic Act) specifically authorizes FDA to approve drugs based on clinical trial evidence as such varied quality. Congress has made a policy decisions that FDA should not require that drug approval supported by two trials studying clinical endpoints. The authors suggest that FDA adopt a “life-cycle” approach for drug safety and effectiveness, communicating a therapies risk and benefit information in an updated summary that distinguishes between the types of evidence relied on for initial and continuing approval. It also requires adequate and robust post-market surveillance systems that allow for re-assessments of drug efficacy and safety after launch.

This study is in hopes to educate the public about what kinds of evidence actually support many drug approvals. Its important for patients and practitioners to understand the quality of evidence that supports drug approvals because the quality of that evidence goes to the amount of certainty we should have about the safety and effectiveness of a drugs. This study also increases knowledge about the relative strength of the evidence supporting many drug approvals, it can also enable a more informed debate about whether Congress and FDA have struck the right balance between allowing access to effective drugs for patients who need them, and preventing harms from access to ineffective and unsafe drugs. 

References:

http://jama.jamanetwork.com/article.aspx?articleid=1817794 

http://www.news-medical.net/news/20140122/Study-shows-clinical-trials-used-by-FD-to-approve-new-drugs-vary-widely-in-characteristics.aspx 

http://www.healthnewsreview.org/2014/01/jama-papers-on-the-fda-drugs-and-devices/ 

http://www.sciencedaily.com/releases/2014/01/140121164758.htm

Timothy Leary Changing the World

Dr. Timothy Leary was one of the most prominent figures during the counterculture of the 1960s, and since those times has remained influential on music, pop culture, television, literature and film. His popular slogan, “Turn on, tune in, drop out”, persuaded millions of people to take drugs and explore alternative lifestyles. Leary’s main message – and another one of his famous slogans – was to get people to think for themselves and question authority. It’s a message that’s still relevant today. When LSD was made illegal in 1967, Leary’s went from being an active leader to being mainly a symbol. The government decided that it was going to make an example of Leary in its war against drugs. President Nixon even called him “the most dangerous man in the world.” While making LDS illegal, it didn’t decline the use of the drug, if anything it increased it, but it did change the way the psychedelic movement was developing. The music festivals came to an end mainly because possession of LDS was now a misdemeanor and selling was a felony.

Instead of looking at the medical evidence provided to them, the government made the choice to make LSD illegal based on their fears of the recreational use taking place. Without any real medical reasons to ban such drugs, as well as the possible benefits that increased research could discover, it begs the question why was the government so afraid of what this psychedelic movement might produce? The government was afraid of the radical counter-culture, and their calls to change the establishment. Many people in the government viewed drugs such as marijuana and LSD as the fuel for this counter-culture, so it only would make sense to cut it off as its source.

If our country can legalize alcohol and cigarettes, why not marijuana for recreational use?

Fifty years ago, the idea of marijuana being legalized would have seemed outrageous and impossible to most people. Attitudes regarding marijuana regulation have also changed as some states - Colorado and Washington - have passed their own laws legalizing marijuana for recreational use. If marijuana is legalized in all states, it will dramatically influence the future of American culture, particularly its economic, social and medical structures.  Marijuana smoking, while thought to affect the brain and body many times long after one has stopped using the drug, is generally not any more harmful than alcohol or tobacco if used in moderation. So what’s the problem? Legalization of marijuana would likely mean a lower price of the drug and reducing related crimes. It would also be a source of additional tax revenues and police would be freed up for more serious crimes. The problem is that people are used to thinking that marijuana smoking is “bad.” We have forgotten that drinking used to be “bad”.

Legalizing marijuana will open the door not only to an improved healthcare system, but also to an improved economic and social structure. It also is fulfilling Timothy Leary’s transform America movement. The only question is whether the American people will have the courage to take the risk.

References:

Timothy Leary 

Transform America 

The War On Drugs 

 

Risks

I believe that risk is an important part of living a good life. Without taking risks, you cannot truly live – you merely exist. Risk doesn’t need to involve danger; it only needs to involve uncertainty. Four of the top risks in my life include:

1.    The risk of being hurt

Everyone has his or her heart broken more than a few times – as well as break some hearts. I occasionally argue with my closest friends or cry because time is passing too fast. I take the risk of losing someone that I thought I couldn’t live without. This is all what happens when I open my heart and mind to the greatest joys of life. Anybody who is capable of living and loving is bound to get hurt at some point, but that’s the risk that’s well worth the reward. It’s important to laugh too much and love like you’ve never been hurt because life is too short to let it pass by.

2.    The risk of possibly failing

I challenge myself everyday. As I conquer challenges that stand in my way, I find confidence in my abilities. Having confidence is significant in the path of success.  It’s important for me to get comfortable with being uncomfortable. The reason life can be so rewarding is because nothing is guaranteed. My many failed attempts are simply evidence that I am reaching higher – which is always the best direction to go. Some of my best life experiences and opportunities have come after I dared to lose.

3.    The risk of letting go and starting anew

Holding on to what’s no longer there has always held me back. I must accept the end of something in order to begin to build something new. This is important to me right now since I am in the last semester of my college life. I will be starting a new chapter out in the real world and I need to be able to let go of my college life here in Athens to make room for more wonderful things to come. I must not waste anymore of my time trying to live in another time and place.

4.    Everyday risks

The world is an inherently risky place with unpredictable twists and turns, regardless of how many safeguards we put into place to avoid then.

-       Driving: I speed when I drive and risk my life the minute I get into my car. I drive a small car that roughly doubles my risk of those that drive a larger car.

-       Stairways: Should be simple right? But falls kills 16,000 people per year. Every morning when I take the stairs of my old 3-story apartment, I risk falling.

-       Coffee: I drink a cup of coffee a day with my breakfast. It contains caffeine, a well-known stimulant that may be carcinogenic.

-       Tanning bed: I use the tanning beds almost everyday, especially a lot in the wintertime. I’m really putting myself in a greater lifetime risk of developing skin cancer. 

I am very aware of the risks in my everyday life, but that doesn’t mean I will ever stop doing them. Risks are uncertain and unpredictable but they allow you to grow and discover new things about yourself and the world.

Life doesn’t come with any guarantees.

References:

- Letting go

- Understanding risks

- Challenging yourself