By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical
My recent article on transparency in clinical trials, featuring Dr. Brad Thompson, CEO of Oncolytics, solicited a good number of comments and emails from readers. While most readers agree that more transparency would be good for patients and the industry, there seems to be a lot of disagreement over how it can be achieved, and if it can actually be achieved at all.
To recap, Thompson believes we still have a long way to go, and questioned whether true transparency would ever be achieved. His primary argument noted researchers who want to be published will not put much focus on neutral or negative trials, and even the press releases put out by sponsors include a limited amount of information.
One reader that works for a CRO made the following comment: “Dr. Thompson from Oncolytics made some very interesting comments about investigators holding back information. An investigator will enter patient data into an EDC system that is then verified by monitors. And that is just one of a number of sites. These investigators will generally know when a drug is working and when it is not. As a CRO, I often saw statistical outputs on blinded studies where you could see where the data was trending. Even data guys can tell if a drug is working by the data results and improvements in patients.”
If physicians and researchers are able to see clear results even when the data is still in the process of being collected, then what is the problem with being more transparent? One possible explanation is that once physicians know a drug will not work, they will no longer continue to place patients at risk by having them participate in the trial. This could be done for purely ethical reasons.
But there may also be reluctance to greater transparency on the part of the pharma company. “No drug company truly wants transparency because it leaves the results and outcomes more open to interpretation, mainly by Kaiser, Blue Cross and other groups,” noted another reader. “Pharma companies could cost themselves a lot of money in sales if they do not have the time to target and position.”
Investors Are A Consideration
There is still another consideration at play. If a study is not going well, would it be to the benefit of the executives of a company to share those results? Let’s play devil’s advocate for a moment and assume you are the CEO of a biotech company. You’re making $500,000 a year with good benefits. You have several investors who have dumped millions of dollars into your company and your product. The study is targeted for four years, but within the first year you see results that indicate your drug is not going to produce the intended results.
“In that scenario, how prone would you be to ending the trial, saving the investors their remaining money, and losing your job?” notes one reader. “Are companies prone or pressured to locate new targets for therapy or identifying reasons to extend the trials, sometimes for a few years or longer?”
All of us have heard discussions about the possibility of electronic medical records (EMRs) someday replacing electronic data capture (EDC). According to one email I received, this will never happen because of the physician issue mentioned above. After all, if patient results were posted in the EMR and every doctor on the network has access to the information, everyone would know if I drug was not having the desired effect. As soon as that happens, promises of riches being delivered to investors will fall by the wayside, and executives will be out of jobs.
“Within big pharma, this is called job preservation,” noted another reader. “If funding for the trial is cut, I am out of a job. At the same time, trial results are not getting any better for patients. Years ago about one in three trials resulted in a successful outcome. Then it went to one in four. Today that success rate is around 15 percent with R&D commitment at about 12% (down from approximately 28%). It appears that the industry is run by money and managed by guys who know how to play the system. If patients are the primary concern, the industry would target physicians who have the right patients, get enrollment done faster, and quickly identify if the product works as advertised.”
Limit Procedures And Additional Fields
Going back to Thompson’s comments, the problem is not always investigators wanting to get published. One reader noted oftentimes it is the in-house pharma and biotech doctors as well as researchers in academia who are anxious to get their names into publications. “Unfortunately, these are often the same people who include numerous unnecessary procedures in protocols. They will also ask for additional data fields to be included in EDC systems after study launch, which can delay database activity for two months. The reason is they see a hint of something and decide they want to dig deeper, even if the activity has nothing to do with the study results and the overall goal of the trial.”
The obvious fix to this would be executive leadership and study teams standing up and challenging the reason for inclusion of the additional data fields, which cost the industry both time and money. A large number of procedures should be challenged as well, especially if they are not standard of care.
“If a researcher sees a hint of something that seems to be interesting but has nothing to do with the study, they should engage one of the thought leaders to conduct an IIR program to see if the hypothesis is valid,” notes the reader. "They can do this while keeping the clinical program on track to closure without delay, and still appease their interests.”
Clearly, there are no easy solutions. Many pharma companies are certainly making a concerted effort to put the patient first, and I believe those efforts are sincere. But there is no question they must also be focused on funding and trial results - the industry has gone from one focused on a patient to one driven by investors, and that trend is unfortunate. Physicians and researchers will always have their own goals and aspirations, and placing additional burdens upon them could have the unintended consequence of driving them away from trial participation - poor sponsor/CRO pay practices and poorly written/detailed protocols have already moved many physician practices away from clinical trial participation. Coming up with a solution will likely involve bringing together all stakeholders for a more in-depth discussion on the topic, which unfortunately I don’t see happening anytime soon.