Dear All,

Apologies for the delay in blogging . . . we recently had a death in our family. Actually, it was my Father-in-law, who lived to be 81 despite suffering from heart failure, high blood pressure and COPD. If you take away the last 6 months, he actually was a modern medical miracle. I would like his case study and that of my own father, who is also 81, to be the subject of this blog. Not personal stuff, although both of them are truly great men, who represent the “greatest generation” in more ways than one. Each were the children of immigrants, growing up poor during the depression, serving as very young men (18) in World War II, married (each for 56 years, and in my parents case, still counting), and contributors to the baby boom. Each was blessed with good health until their 70’s. That is when their lives and my profession came together.

In the case of my Father, who is still living, when he was 77 he came down with a routine case of pneumonia. He was treated with antibiotics and developed a rare adverse drug reaction, which led him to go into acute renal failure. (I know what you may be thinking…I spend 20 years reporting and reviewing SAEs and my father was one – the irony was not lost on me). Since that time, he has been on dialysis three times a week. The impact of this on his life has been dramatic, but not devastating. My Dad never liked shots, so having giant needles inserted at 6 am on Tuesdays, Thursdays, and Saturdays is a test of his resolve, but then so is sitting still for 3+ hours. He has also had to modify his diet and severely restrict his liquid intake. As a side note, my parents are part of the “cocktail” generation as well, so when 4 pm comes around, my Dad has reserved at least 4-8 oz of his total volume intake for his “drink”. Mind you, his total volume allowance is 32 oz., so this shows a lot of discipline in my mind. My Dad still plays golf regularly (he lives in Florida), takes care of his own yard (including fruit bearing trees) and does his own home repairs, not to mention all the puttering he does in the garage. He is in extremely good health and has recently been placed on the kidney transplant list. If he is fortunate enough to receive a new kidney, he will be placed on a regimen of meds that was unthinkable when he was born. If you look at the benefits/risk equation just for him, it is weighted heavily on benefits.

Now, if you move on to my Father-in-law, God rest his soul, when he was in his 70’s he underwent a grueling open heart surgery that resulted in 8 bypasses and a new (synthetic) aortic valve. His recovery was slow, and in some ways never complete. His postop drug regimen was extremely complicated, made more so by the necessity to be on Warfarin to prevent blood clots, but which for him was extremely difficult to regulate. He developed heart failure after the surgery and it progressed despite aggressive therapy. He also developed chronic obstructive pulmonary disease and adult onset diabetes. This led to cycles of pneumonia/bronchitis, the treatment of which affected both his coumadin and blood sugar levels, and over the last 2 years he was hospitalized numerous times. Somehow he always rallied and was at all the family gatherings that celebrated birthdays, holidays and anniversaries. In this time, we were all blessed with a new family member, a little girl adopted from China. She was one of the few bright spots for him in this time. His benefits/risk equation tipped before our very eyes.

This is all a very long introduction to the real subject of this blog - Benefits/risks and how it is ascertained. I think sometimes we forget in the throws of creating applications, as the actual benefits/risks statements comprised such a small piece of the overall summary [i.e. in (e)CTD it appears as M2.5.6], but it is at the heart of all we do. I recently heard a medical reviewer speak at a conference stating that after 20 years there will finally be guidance from FDA on Integrated Safety and Efficacy coming next year. He pointed out something that I hadn’t thought of in a long time however, and that was how “easy” it is to measure benefit (efficacy) as it is either there or not, there are endpoints and analyses and with the exception of Quality of Life, which is difficult to measure, you can usually literally point to it. But with safety, there are no real analyses and you often don’t even know what to look for! Yet we are a risk adverse population and regulatory people, by their very nature, don’t embrace risk.

This whole concept is what is driving a lot of the PDUFA IV (Safety) goals for the next 5 years and what will mandate standards in clinical data and documentation. We have to give FDA a way to at least look across the “landfill” of data give them a way to mine it. This will certainly affect me personally as that is what I do – I compile data and documents. I actually envision my own quality of life improving and can only hope that this extends to the public as well and most especially to those patients who are each trying to balance their own benefits/risk equation!