There are many advantages to working in clinical research, mainly intellectual. To me the best part of the job is thinking up interesting ideas, figuring out ways that one’s ideas can be found to be correct or not (called “hypothesis testing”), and hoping that what you discover might eventually lead to changes in human health. Like most good things in life, though, there are annoying challenges that come with the good. At the front of the line is rejection. Ideas are discussed and determined to be nonsense. Once something is found scientifically and a manuscript written, a journal says, “no thanks.” And then another journal says the same thing. And another. At the top of the rejection heap is obtaining grants.
A grant is money that is used to implement a project. The largest funder of medical research world-wide is the US National Institutes of Health (NIH). NIH-funded grants are desirable for several reasons. The applications are reviewed by leading scientific experts and only the best get through. Budgets can be for a great deal of money, more money than smaller institutions can offer. And NIH grants carry a monetary bonus (called the “indirects”) for the institution that is lucky enough to receive one. (When I apply for an NIH grant, my university or hospital submits the application on my behalf. They receive the money, keep the indirects, and then hand over the money to do the project [the “directs”] to me.) Though receiving funding from anyone (the Gates Foundation for example) is wonderful, NIH grants carry prestige with them, and the competition is fierce.
Writing a Protocol is a lot of work. One must think through all the actions of those caring for the patients, but also consider everything that might possibly go wrong, and what the response should be if that happens.
Currently I am in Malawi working as a co-investigator (not the Principal Investigator or “PI”) of an NIH-funded clinical trial, “Treating Brain Swelling in Pediatric Cerebral Malaria (TBS).” This is a Phase 3 study that evaluates two adjunctive (used in addition to the standard of care) treatments for pediatric cerebral malaria. This project, like many others being conducted here, is overseen by the Blantyre Malaria Project, or BMP, headed by Dr. Terrie Taylor.
Two years ago, a group of laboratory scientists who work for the NIH approached Dr. Taylor about a new adjunctive medication for cerebral malaria that they had developed. I was assigned to work on this new idea with them. The drug’s acronym was “DON” and it was remarkably effective in animal models of the disease. Since I was in Washington DC, I went in person to the NIH campus (in Maryland), met with the scientists, and learned about their discovery. After an initial flurry of meetings, they asked me to create a clinical trial Protocol for a possible future study of DON in children with cerebral malaria. A Protocol, typically 70-100 pages, governs the actions of the physicians and nurses conducting a clinical trial, a study where patients are assigned different treatments to evaluate safety or efficacy, the ability of an “intervention” (DON in this case) to make better or cure an illness. Writing a Protocol is a lot of work. One must think through all the actions of those caring for the patients, but also consider everything that might possibly go wrong, and what the response should be if that happens. In the past I had helped write Protocols but never created one by myself.
Amazingly, I had a temporary lull in the many tasks that make up my job. I agreed. It took several focused weeks of work but at the end of 2 or 3 months, the NIH scientists received what they asked for. I thought that was the end of my being-nice-to-nice-people involvement with DON.
But life had other plans. The NIH scientists read the Protocol, liked it, and asked me if I would lead (be the Principal Investigator of) the clinical trial in African children they hoped would take place with DON. Being a Principal Investigator is a lot of work. I thought about it for a few days, consulted colleagues, but eventually consented. This meant writing a grant to implement a Phase I (assessing safety) clinical trial of DON, a very time-consuming and all-encompassing task. But after a few months of dedicated work (and a lot of help from others) I submitted the grant application to the NIH. At 365 pages, it was the longest thing I had ever written.
Grants take months to be reviewed. After review, the applications are ranked in order of “scientific merit” and assigned a percentile rank. A lower number is better. After months of waiting, the DON application was assigned the 14th percentile, excellent and maybe fundable but maybe not. The NIH sets the percentile rank below which they will fund grant applications. This number is called the “payline.” If the DON application had been submitted the previous year, we would have received the funds as the payline was 14. But, unfortunately, it was no longer last year and the current payline was 10. Maybe the payline would go up to 14 later in the year, but maybe it wouldn’t.
The responsible person at the NIH (called the Program Officer) gave me this news. He thought things looked favorable for receiving funding, but unless the application had a score of 10 or below, there could be no guarantees. He suggested I quickly revise and resubmit the application, hoping it would receive a score of 10 or below on this go-found. The deadline was 3 weeks away.
I cleared my schedule and went to work. And after more help from others, three weeks later we submitted the revised application. The resubmission was 437 pages long, once again the longest thing I had ever written.
Again we waited. And waited.
Seven days ago, the day I arrived in Malawi, the expert physicians and scientists at NIH reviewed the revised DON grant application and the applications from the competition. They discussed and ranked them. Afterwards, each application was assigned a percentile rank. And today the NIH released the results.
We received a six.
And six is less than ten.
