Are Clinical Trials Safe?

The Government recently put its weight behind increasing the number of clinical trials in the U.K., increasing the number of people enrolled in them and speeding up the MHRA’s licensing based on the trials data. (Here’s the Government’s announcement and the O’Shaughnessy Report on which it is based.)

I’ve been critical of MHRA since I uncovered failures in its licensing and monitoring of medicines which I wrote about here. Those articles led to me being a co-author of the Perseus Report, which was sent to all MPs and Peers in April. So, knowing that MHRA also regulates clinical trials, I decided to take a closer look.

First, let me say that of course I realise that clinical trials are, in principle, a good thing. Otherwise, new medicines wouldn’t get to market. I’m just concerned, as with the Covid vaccines, about the safety of clinical trials and the principle of fully informed consent.

Before I even got to researching the MHRA’s role in regulating clinical trials, I found a few wider issues that you should consider very seriously should you ever be tempted to enrol – the sorts of things they don’t tell you about in the ‘Informed Consent’ document for trial participants.

The first thing you need to know is that a lot of the motivation for this is money – big money. And I don’t mean that some commercial trials pay you to participate. I mean that you participating in a trial saves the Government money and increases the profits of pharmaceutical companies. Let me explain.

Here are a few quotes from the O’Shaughnessy Report which underpinned the Government’s initiative:

“The U.K. life sciences sector had £94.2 billion in turnover in 2021.”
“Commercial research… generated £1.8 billion to the U.K. economy in 2018/19.”
“The NHS received about £355 million in 2018/19 from life science companies and saved about £29 million from pharmaceutical cost-saving, where a trial drug replaced the standard of care treatment.”
“The NHS receives about £9,000 for each participant recruited onto a clinical trial and saves about £6,000 per participant due to treatment costs being covered by the commercial sponsor.”
“If the patients enrolled in commercial trials had remained at the same level as in 2017/18 (rather than reducing), the NHS would have generated an estimated £570 million in income, and £360 million in savings.”

The next thing to know is that the pharmaceutical companies’ business model has been in trouble for the last 20-plus years. Their business model revolves around identifying promising new molecules, testing them in small, medium and then large clinical trials to gather safety and efficacy data, putting those data to the regulators and, hopefully, bringing new drugs to market. It requires very big investment over a long timeframe. Getting a new product to market takes on average 13 years with a low probability of success. One assessment by Bain & Co was that in 1995-2000, the ‘failure rate’ averaged eight to one. In 2000-2002, it had increased to 13 to one. Their Internal Rate of Return has been steadily decreasing for years with a steep decline between 2010-2014. You can read more yourself about all this here, here and here.

Big Pharma has made significant efforts behind the scenes to get Governments in the U.K., Europe and the US to help them to protect and improve their profits. For example, in the U.K., a Ministerial/Pharmaceutical Industry Strategy Group (MISG) was established in 2010. The minutes make interesting reading. For example, in the November 2014 meeting, Patrick Vallance (working for GlaxoSmithKline at the time) said: “In the future, medicines will come to market quicker with less data with more research being conducted in the post-license phase.” Feeling worried?

As an aside, I think that MISG must have been renamed the ‘U.K. Life Sciences Council’. See here and here. Also, Twitter reveals that Rishi Sunak is personally involved. But that’s another story for another day.

Anyway, back to clinical trials. I’ve already described the financial benefits to Big Pharma and the Government of you enrolling in a clinical trial.

It has, of course, also to be said that participating in a clinical trial can benefit you medically if you suffer from the disease or condition under trial – but only if you don’t receive the placebo or partial dosage and the trial medicine actually works. You might even get paid to participate. And even if you don’t have the relevant disease, the trial medicine can also benefit the wider public if the trial is successful and the medicine gets to market. However, as noted above, about 90% of trial drugs fail to meet safety or efficacy criteria.

So much for benefits. What about risks?

First, the MHRA, which licenses clinical trials in the U.K., has a poor track-record and is under-staffed, not just in quantity, but in terms of suitably qualified and experienced staff. The Government is obviously worried about this too because it says it has given MHRA extra funding. However, this is classic smoke and mirrors – it’s just reversing the funding cuts the Government imposed on MHRA in 2020.

Next risk? There is an increasing trend of less face-to-face clinical contact during drug trials. Doesn’t sound to me like that will improve the safety of trials participants!

Then there are the MHRA’s failings in regulation highlighted in the Perseus Report. For example:

No independent safety audits of MHRA
No separation between regulation (rule making and enforcement) and safety management
No individual responsibility – it’s all done by groups of assessors
No system for senior management governance of safety
Significant conflicts of interest
Lack of transparency

These apply to MHRA’s regulation of clinical trials just as much as they do to its Licensing and Pharmacovigilance of public use of medicines.

What about speeding up MHRA’s approvals of clinical trials? Just to point out that Dame June Raine has publicly declared MHRA’s purpose has changed from Watchdog to Enabler. Say no more.

Next, there’s a risk relating to investigation of safety incidents arising in clinical trials. It’s vitally important to accurately describe every single adverse event which arises in a clinical trial as unrelated, possibly related or most likely related to the drug under trial. This process directly drives calculations of safety risk and efficacy. When I worked in the Ministry of Defence, we caught out some defence contractors trying to ‘disguise’ problems in trials by dubious sentencing of incidents as being unrelated to the weapon under trial. Many pharmaceutical companies also have form in this regard and we saw it most recently with the Pfizer and Moderna Covid vaccine trials which were re-analysed here. MHRA therefore needs a robust process for rigorous checking of Pharma’s sentencing of all suspected adverse events during a clinical trial. Feeling confident? I’m not. MHRA admitted that it doesn’t have a process for investigating Yellow Card reports of adverse events potentially linked to medicines in public use. So what are the odds it has a process for investigating adverse events arising in clinical trials? Let alone a robust one. I will be submitting an FOI request to MHRA to check this out.

Finally, if, God forbid, a clinical trial does injure or kill people, guess who will investigate? The MHRA! As it did with the infamous Northwick Park tragedy in 2006 from which it absolved itself from any blame.

So if you want to enrol in a clinical trial, you go right ahead.

Until Nick retired a few years ago, he was a Senior Civil Servant in the Ministry of Defence responsible for the safety and effectiveness of ammunition used by the Armed Forces. He is co-author of the Perseus Group report on U.K. drugs regulator the MHRA.