In June 2017, Yale CRIT hosted an international conference titled “Ensuring Safety, Efficacy, and Access to Medical Products in the Age of Global Deregulation.” The following blogpost is the second installment of a blog series with commentaries from the conference participants. The views and opinions expressed in this blog post are those of the author and do not necessarily reflect the position of Yale CRIT. For more blog posts related to this series, see here or click the tag “YaleCRIT17” below.
Firstly, the chance to be involved in this conference has been very useful and is appreciated – especially bringing together such diverse backgrounds and interests.
As an HIV positive activist, I am lucky to have benefited from both antiretroviral drugs (ARVs) and cancer drugs. These drugs work. But it is because of treatment literacy that I understand how these drugs work. I have had the chance to learn about my health from other community projects that explain science and medicine in easy to understand language.
The proposed changes to lower regulatory approval standards are extremely worrying, and it is not an accident that this is happening in the U.S. and Europe at the same time. These proposals are being driven by financial greed and profit rather than for better health, and some so-called "patient organizations" are being manipulated to support the changes.
Deregulatory movements are being so strongly marketed and branded as common sense: "I am sick – I want treatment.” To understand the power of this simplified idea, think of situations when you have been a patient. And if you have not had this experience yet, then you will have it in the future. When faced with a life-threatening illness, it becomes very easy to drop science, logic, and data in grasping for hope.
One of the challenges of resisting the simplistic view that patients just want medicines, is that from a non-technical view, there is little transparency in the proposed regulatory changes. The proposed changes have so far involved a mix of political spin and lobbyists.
This is unfortunate given the long history of HIV activism and its primary focus on the highest quality evidence for both efficacy and safety. The history of HIV drugs includes both incredibly positive results and very negative results. Many drugs, especially when used in the right way, turned a fatal disease into a manageable infection. But among the thirty or so individual drugs, some were much better than others, and others failed to receive approval even after phase 3 studies.
Examples of drug failure from HIV are important to counter the “right to try” argument that underlies much of the deregulatory trend. Some HIV drugs were approved even when they had little benefit and were found later to cause significant harm - even after phase 3 studies led to approval.
We need better drugs, and there is a huge potential for rational drug development to identify better drug targets and early compounds, with better pharmacokinetics data and fewer potential drug interactions.
For HIV, the move to allow drug approval based on improved surrogate markers rather than hard clinical endpoints (such as disease progression and death) was essential, not least for ethical reasons. This benefit was because both CD4 counts and viral load are very good surrogate markers for ARV efficacy. But the CD4 count was not appropriate for immune modulator IL-2, and viral load only worked as a surrogate under specific circumstances (i.e. reaching a lower target, not just a reduction).
For cancer treatments, the limitations of having so few surrogate markers means that people have to use the highest tolerable doses, and then wait for years to find out whether this was ultimately successful. The options for dose modifications are extremely limited and primitive compared to HIV treatment.
HIV treatment activism also has a long and specific history with early access programs (EAPs) for drugs that are not yet approved. This demand for early access was dependent on sufficient efficacy and safety data and the need for life-saving options. Earlier access was justified to cover people who were excluded from enrolling in clinical studies – perhaps because they were already too ill from either HIV or related complications.
In practice, most EAPs were for drugs where phase 3 studies had been completed, so that placebo-controlled studies were not destabilized by people opting for guaranteed access to the study drug. The ethical demand for an EAP was that once phase 3 studies were completed and approval was likely, the bureaucracy of access would be too late for people who had a high chance of either dying or seeing their condition significantly worsen during the six months needed for regulatory approval.
Thus, most HIV medicines that became available on EAPs fulfilled a role in keeping people alive and in better health for longer than if they had not been available. An example of a negative EAP was for adefovir, which enrolled almost 9,000 participants for a drug that ultimately was never approved due to high risk of kidney damage and limited antiviral benefit with the 60 mg and 120 mg doses studied. Adefovir was later approved as a treatment for hepatitis B using a daily a dose of only 10 mg.
Finally, post-approval concerns raise the need for more data beyond phase 3 studies, and yet already companies often never fulfill post-approval phase 4 studies. Ultimately, some drugs are approved based on results from a thousand people and then used to prescribe treatment for millions of people. Post regulatory evaluations are clearly essential. In response to the proposed deregulatory changes, we need better arguments to support science as having the simple ability to prove benefit and risk.
Simon Collins is an HIV positive treatment advocate at HIV i-Base, which he cofounded in April 2000. HIV i-Base is a treatment activist group committed to providing timely and up to date information about HIV treatment to HIV positive people and to health care professional