How to find a clinical trial

Table of content

Half of all Melanoma patients still need experimental medicine.

for starters

So what do we as MPNE community do about clinical trials?

A simple truth: trials that don't recruit get amended.

The Triple challenge of clinical trials

Half of all Melanoma patients still need experimental medicine.

​In 2011, the year the first new Melanoma therapy was approved, about 5% of all patients with Advanced (Stage 4) Melanoma were still alive after 5 years. Today, about 10 years later, over 50% of all patients are- read about the ASCO 2022 update of the study KEYNOTE-067 here.

 

The progress is remarkable but it also means that current therapies only work for half of all Advanced Melanoma patients in the long run. The other half- those whom even the new therapies fail- are most likely to receive some form of experimental treatment. 

'Experimental treatment' might sound like the very last thing one wants to hear when having to deal with advanced cancer. Except for the alternative....

Treatments can be experimental in different ways- it can be simply using therapies in a way that makes sense but for which there is no solid evidence, so no one knows how well they will work.

 

However, the most known part of experimental medicine are clinical trials.

It is worth remembering that not everyone who joined a clinical trial in the last 15 years survived. But those who did survive all had some type of experimental treatment- as it was the only way to access anything with a chance to work.

Experimental treatments are not created equal. The degree of 'experimental' can vary considerably, from 'never tested in humans before' to 'highly likely to work'. Knowing how to find, chose and to navigate the clinical trial system is therefore a valuable skill. Here some pointers that are probably the most honest you will find on the internet.   

 

for starters

The following is only relevant if you consider a clinical trial to increase your chances to survive Melanoma (or a similarly serious condition, though some of this is cancer-specific), otherwise, it doesn't matter which trial you join.

Clinical trials are big business and make careers and are therefore full of vested interests. Understanding these helps you to chose a trial that is actually in your own, not just everyone else's interest, and not to fall prey to the more or less open moral pressure patients are constantly subjected to.

The Helsinki declaration clearly states in Article 8 that the interests of the person participating in a clinical trial takes precedence:

'While the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects'

Unfortunately, this is not always the case. We have seen that patients are often put under unfair moral pressure 'if you don't go on this trial, we will never get new drugs'. Patient advocates get to hear that is better to sacrifice - yes, you read that correctly- single patients on clinical trials 'for the greater good of society (this usually means cost-effectiveness calculations) and future patients'.

This clearly violates what Helsinki says: 'interests of the individual research subject take precedence' and BR has published a commentary on this: No interest can take precedence- a patient perspective on oncology drug development. Full text free access here: https://go.nature.com/2WJVYBu  

As MPNE and fully aligned with the Helsinki Declaration, the interests of the single patient on a clinical trial come first, so we are after trials that are good for every single patient on the trial. And we work on better trial designs: the ideal trial is one that is good for patients on the trial AND patients outside the trial.

 

So what do we as MPNE community do about clinical trials?

- we educate and help patients find the clinical trial that is best for them

- we argue, eh discuss, with decision-makers like regulators, HTAs, academics- that's why you will find us on various conferences on the topic and some of it is published, you find the MPNE publications on this page- about patient-friendly trial designs that still answer the important regulatory, health-economic, clinical and research questions

- we educate and learn broadly and inclusively about Melanoma, Science, research, healthcare systems and teach necessary skills- anyone who wants to learn is welcome 

And that works?!

Yes, it does. Over the years, we have met impressive people in every other single stakeholder group- people who truly care about making a difference in cancer. Every other stakeholder group is there for a very valid reason and has its own constraints.

In the past, patients just didn't have a say and were simply subjected to what the other stakeholders worked out among themselves, catering for their own (valid) interests and constraints- unfortunately, the end result wasn't always good for patients, despite everyone claiming to work in 'patients' best interest'.

Today, with patients expecting more than lip-service and imposing their rights, this means a re-adjustment of the entire system and change is never easy (there are entire book shelves on change management) 

 

But then, there just is ....

A simple truth: trials that don't recruit get amended.

Trials that don't recruit get amended. Amendments cost money and time.

Cost is one of the biggest problems for trial sponsors. That means helping patients to identify those trials that are good for them means good trials recruit and poor trials get amended until they are good for patients. And it also means future trials look different as oddly enough, as soon as money is involved, there suddenly always seems to be a solution to all those 'impossible' problems.

(there are also entire book shelves on that incentives do work).

 

 

 

So, to the point: The Triple challenge of clinical trials

 

When it comes to clinical trials, there are 3 challenges:

  • how to find them,

  • how to chose the most promising one, considering circumstances 

  • how to access them.

All these are complicated by the fact that the clinical trials space is full of vested interests: Pharma companies need them to get their products approved, oncologists need them to have something to offer to their patients, for their careers and in some places to get their qualification; trial centres make money by running clinical trials; CROs (contract or clinical research organisations) are paid for running clinical trials; you can make money by recruiting for clinical trials. A quick web search on 'clinical trial recruitment' will give you an idea about the issues.

Clinical trials and how to find them

There are endless websites out there where you can search for trials. The 2 main challenges for finding relevant trials are 

1. the databases you are searching

2. the algorithm with which you search.

 

Unless you know what you are looking for, you want to make sure to search a database that is as complete as possible, up-to-date and not biased. Pharmaceutical companies e.g. have their trials on their websites but you will obviously only find THEIR trials on there and even if they link you out to unbiased sources you can be sure they will do their best to promote their own trials first. Well-intended sources frequently have the problem of not being up-to-date as well as a selection bias- what someone else thinks relevant might not be your idea of relevant.  

Websites 'simplifying' trial searches for patients come with a number of issues, partially linked to some of their business models, partially linked to their search algorithms intended to simplify the search experience for patients. If you consider using a platform to search for trials, it is worth checking out their business model in detail to see whether you agree with it and whether it risks to bias the results you are getting. If they are working with certain companies, check which databases they search, so covering ones or just thec company ones and whether there are any weights in the way the present results. Trial referral pays, so it could e.g. be that trial options are presented in the order of who pays most for a trial referral- you don't want that. Also, many platforms ask you to submit quite a lot of information about yourself- do they sell that on? Especially when using US-sites, be aware that their data protection laws are weak. You might just be submitting a lot of your personal information in the hope of finding a trial which they then happily sell on without you ever seeing anything in return...

Search algorithms intended to simplify the search experience for patients often use pre-set criteria to search larger databases like clinicaltrials.gov. While it reduces the number of results you get, it has certain challenges. Clinicaltrials.gov inclusion and exclusion criteria are overall in rather not a good shape- they tend to be incomplete and at times contradictory, so solely relying on that is not a good idea. Pre-set geographic criteria can also be problematic- if you indicate you are willing to travel 50km and there is a great trial at 51km you are bound to miss it...

Thankfully and increasingly, clinical trials, in particular those for new medicines, need to be registered in certain places- academic trials unfortunately tend to lag behind- that means that these databases are unbiased in that respect and up-to-date.

We have found over the years it's wiser to invest time to learn to search these original databases rather than trying to figure out biases behind nicer-looking tools.

The least user-unfriendly one is https://clinicaltrials.gov/.

The website gets updated daily and was re-designed a while ago in an effort to make it more user-friendly. While it's still complex it has a lot of information and help to get started, including

An introduction for patients

A 'how to search' section

A glossary

You can even set up your own RSS feed

And very importantly, the background to the site,

an extract- 

What Is ClinicalTrials.gov?

ClinicalTrials.gov is a Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions. The Web site is maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH). Information on ClinicalTrials.gov is provided and updated by the sponsor or principal investigator of the clinical study. Studies are generally submitted to the Web site (that is, registered) when they begin, and the information on the site is updated throughout the study. In some cases, results of the study are submitted after the study ends. This Web site and database of clinical studies is commonly referred to as a "registry and results database."

ClinicalTrials.gov contains information about medical studies in human volunteers. Most of the records on ClinicalTrials.gov describe clinical trials (also called interventional studies). A clinical trial is a research study in which human volunteers are assigned to interventions (for example, a medical product, behavior, or procedure) based on a protocol (or plan) and are then evaluated for effects on biomedical or health outcomes. ClinicalTrials.gov also contains records describing observational studies and programs providing access to investigational drugs outside of clinical trials (expanded access). Studies listed in the database are conducted in all 50 States and in 220 countries.

ClinicalTrials.gov does not contain information about all the clinical studies conducted in the United States because not all studies are required by law to be registered (for example, observational studies and trials that do not study a drug, biologic, or device). See FDAAA 801 and the Final Rule for more information. However, the rate of study registration has increased over time as more policies and laws requiring registration have been enacted and as more sponsors and investigators have voluntarily registered their studies.

ClinicalTrials.gov was created as a result of the Food and Drug Administration Modernization Act of 1997 (FDAMA). FDAMA required the U.S. Department of Health and Human Services (HHS), through NIH, to establish a registry of clinical trials information for both federally and privately funded trials conducted under investigational new drug applications to test the effectiveness of experimental drugs for serious or life-threatening diseases or conditions. NIH and the Food and Drug Administration (FDA) worked together to develop the site, which was made available to the public in February 2000.

The ClinicalTrials.gov registration requirements were expanded after Congress passed the FDA Amendments Act of 2007 (FDAAA). Section 801 of FDAAA (FDAAA 801) requires more types of trials to be registered and additional trial registration information to be submitted. The law also requires the submission of results for certain trials. This led to the development of the ClinicalTrials.gov results database, which contains summary information on study participants and study outcomes, including adverse events. The results database was made available to the public in September 2008. FDAAA 801 also established penalties for failing to register or submit the results of trials. In September 2016, HHS issued the Final Rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11) clarifying and expanding the registration and results information submission requirements of FDAAA 801. This regulation takes effect in January 2017.

An account of the development and expansion of ClinicalTrials.gov in response to changes in policies and laws is provided on the History, Policies, and Laws page.

Searching ClinicalTrials.gov does not require registration or personal identification. Because ClinicalTrials.gov is a Government Web site, it does not host or receive funding or advertising from commercial entities or display commercial content.

You will find out clinicaltrial.gov's history here and they are working on making it even better and you can check out the beta-version here

Getting better: The EU Clinical Trials Register EU-CTR

The advantage of EU-CTR is that that contains the European trial sites and a lot of details about the trial protocols. The disadvantage is that you have to wade through a lot of bulky information before getting there....

 

It also finds trials running in the EU that are not listed on the US site- today's search returned 216 ongoing and upcoming Melanoma trials for Europe on clinicaltrials.gov and 284 ongoing Melanoma trials for Europe on EU-CTR. 

You can start searching here.

The advanced search button allows you to quickly narrow down results.

 

About the EU Clinical Trials Register

The EU Clinical Trials Register contains information on interventional clinical trials on medicines conducted in the European Union (EU), or the European Economic Area (EEA) which started after 1 May 2004.

Clinical trials conducted outside the EU/EEA are included if:

  • they form part of a paediatric investigation plan (PIP), or:

  • they are sponsored by a marketing authorisation holder, and involve the use of a medicine in the paediatric population as part of an EU marketing authorisation.

The Register also provides information about older paediatric trials covered by an EU marketing authorisation.

The Register enables you to search for information in the EudraCT database . This is the database used by national medicines regulators for data related to clinical trial protocols. The data on the results of these trials are entered into the database by the sponsors themselves and are published in this Register once the sponsors have validated the data.

The EU clinical trials register has been a primary registry in the World Health Organization (WHO's) Registry Network since September 2011 and is a WHO Registry Network data provider. It is also available on the WHO International Clinical Trials Registry Platform .

A useful glossary with many terms relevant to the European Union 

 

Clinical trials and how to chose them

Clinical trials and how to access them