An explanation of how the World Anti-Doping Agency decides which substances are included on the Prohibited List

Most sports fans are now relatively familiar with World Anti-Doping Agency (WADA) and the WADA Code (“the Code”), with varying degrees of knowledge. Those who are involved in competitive sport, particularly athletes and coaches, will also be familiar with the List of Prohibited Substances and Methods,¹ known as the Prohibited List (“the List”). The List provides the International Standard for identifying substances and methods that athletes are prohibited from using or attempting to use either in-competition or out-of-competition, in sports that are signatories to the Code.² These substances and methods are “classified by categories (e.g., steroids, stimulants, gene doping)”.³

How effective the Code and the List are at preventing and catching athletes who have committed Anti-Doping Rule Violations (under the Code) is a point of contention within the sporting, legal and scientific communities. This has been highlighted by a number of recent articles focusing on the exclusion of thyroid medication from the 2016 List, including a piece in the Wall Street Journal entitled, ‘In Rebuff to Usada, WADA Declines to Ban Thyroid Medication’,⁴ published shortly after WADA’s announcement of the 2016 List on the 19^th September 2015.

After reading the media coverage of the announcement of the 2016 List, and following the related discussions on social media platforms, I was left wanting to know more about the List, including questions such as:

• What is the process for including or removing substances or methods from the List?
• Who makes the decision at WADA about what is included or removed from the List?
• What is the background of the people who are involved in that process?
• What scientific research is taken into account and how is it weighted?
• How to WADA’s stakeholders, including athletes, feed into this process?
• How difficult, or is it even possible, to create a List that is legally and scientifically robust and one that is athletes can truly comprehend?

To answers my questions, I thought it best to go to the source. So I reached out to Dr Olivier Rabin, Director of Science at WADA, who kindly agreed to explain the process that WADA goes through when reviewing and updating List.

INTERVIEW

Sean: There has been a lot of media coverage around the 2016 Prohibited List. In particular about the substances and methods included on and prohibited from the List and how existing substances and methods that are already on the list are reviewed. 

Can you explain how you go about accumulating the scientific research and evidence to try to get a fair balance between putting things on the List that are overly so that do not punish unfairly?

Dr Rabin: The List of Prohibited Substances and Methods is completed after a well-established, thorough and consultative process. When WADA was established, there was a strong willingness from authorities to be much more transparent and open than at the time the Prohibited List was established by the IOC. The different steps of how the List is reviewed is as follows:

January

In January of each year we have the first meeting with the List Expert Group, which we also call the List Committee. The meeting takes place shortly after the implementation of new List (introduced 1^st January of each year) to see whether there are particular issues raised by our stakeholders or if there are new events that have happened over the recent weeks and months that we should appraise an item on the list.

In the January meeting, the List Expert Group reviews any specific issues and comments we’ve received, and extracts some of the relevant comments that we need to review more thoroughly. This helps us to prepare the agenda for the April meeting. This alson gives us the opportunity to invite some external experts on particular issues, subjects, or themes for which the experts of the List Expert Group may wish to receive further opinions and raise some questions. For example, in the past we had cannabis, stem cells, pain management and narcotics presented to the Expert Group.

April

The April meeting is the first time when the draft List is prepared and the Monitoring Program is reviewed. It is usually a two-day meeting, and again we can invite external experts if needed. At the meeting we draft the List that is then circulated to our stakeholders.

End of April to July

From the end of April to the end of July we circulate the draft List to our stakeholders e.g. national federations, international federations, national anti-doping organisations, anti-doping labs, etc. We ask for their feedback on the List and any changes that are proposed for the new list. It is a vast consultation process.

End of July/Beginning of August

We compile all the feedback from the stakeholders , and the List Expert Group members and the WADA management in the science department review all the comments.

End of August

At the end of August we meet again for two days to review, consider and discuss the comments and identify which ones are relevant, which ones have already been addressed, and which ones deserve more thorough review.

Then when the final draft List is ready, it is moved from the List Expert Group to the Health Medical and Research Committee, which is the working committee for science and medicine research at WADA. This is a completely different group of experts that review the List and provide additional opinions as needed. They’ve got the ability to make changes or adjustments to the draft List.

It is the role of the Health Medical and Research Committee to propose the List to the WADA Executive Committee for final approval.

September

It is typically mid-September when, upon recommendation from the Health Medical and Research Committee, the List is presented to the WADA Executive Committee, where some final decisions can be made or questions can come from the members of the Executive Committee.

It is the role of the Executive Committee to finally approve the List of Prohibited Substances and Methods for the following year.

October

We have a duty under the Code to publish the List at the latest on October 1st every year so that it can be implemented on January 1st of the following year.

January

The new List is implemented.

Sean: Can you give an example of who constitutes the external experts on the expert group?

Dr Rabin: For the Health Medical and Research Committee, every year we receive from our stakeholders the names of experts from different fields (finance, education, research, medical, etc). The Executive Committee then reviews and approves the proposed committee members. Then, a review and decision is taken between the president of WADA, the Director General, and the chair of the Heath Medical and Research Committee to nominate the members of the expert groups such as the List Expert Group. There are two different committees, two different levels for nominations and approval.

For an Expert Group, the decision of who is nominated and approved is based upon the people we know with knowledge in the field and/or people with relevant expertise who volunteer to come. It is important that we have a good mix or expertise in the List Expert Group. We need sport physicians because they know how to deal with the athletes, and they know the practicalities of prescribing or not prescribing substances. We need toxicologists, pharmacologists, pharmacists, physiologists, laboratory experts etc. We need people with different backgrounds who bring different perspectives and expertise.

The terms of Expert on the Health, Medical and Research Committee are limited to a three-year term that is renewable. We do have a regular turnover of experts to provide us with the opportunity to bring in new blood to make sure there is a large or broad view of opinions from different regions of the world, different backgrounds and different expertise coming to these working committees.

Sean: You mentioned that you see a number of comments submitted each year. I should imagine that takes quite a long time to review and consider. Can you give an estimate of how many comments you receive each year during the process?

Dr Rabin: We receive, approximately, more than 100 individual comments each year. This results in 40 to 50 pages of comments to review every year. Some of the comments come from individual stakeholders and some from groups of stakeholders. For example, the Council of Europe, of course composed of different countries, and they have their submission, but also individual European countries can independently send their contribution.

Sean: Based on what you said, it sounds like there is a process for stakeholders to feed into, and considerations will be made if there is something new that comes to light or if any evidence is put forward. Presumably, when it comes to scientific evidence, you have to weight it against the quality of the research, where the research comes from, has it been peer reviewed etc?

Is there a process or guidance note about how a certain piece of research should be weighted when making your decision or is this just discussed within the group of experts?

Dr Rabin: Your point is important, because we don’t of course give the same weight to every comment. We try to remediate the comments where we have received comments at the beginning of the process. Many years ago when some of our stakeholders were saying, “we don’t find it appropriate to have this substance on the list, please remove it, because for us it doesn’t help a lot”. Now we receive submissions that are much more scientifically based; this is what we’ve been requesting. We ask that if people provide an opinion, to have it supported as much as possible with reference to the scientific and medical literature and to testimonies. Some of the anti-doping organisations conduct their own research and we also receive information from the field. All these elements have to be taken into account. We review all scientific literature when it is quoted. However, some of the experiments are very conclusive and sometimes they are not. You may have some discrepancies or contradictions in the science and medical research. It is role of the experts to weigh the science and say whether or not they believe there is a global trend to support certain decisions.

Let me give you the example of pseudoephedrine, because that is an example that was very illustrative of the process. When we were initially reviewing the literature there were studies that showed that it was performance enhancing and others that did not. When we started to review carefully read all the publications, we could start to see there was a ‘dose effect’. In other words, the studies that were conducted with only 60 to 90 milligrams of pseudoephedrine didn’t show much effect on performance. But studies using 160 to 240 milligrams, which is the maximum daily dose for pseudoephedrine, showed some signs of enhancing performance depending upon the nature of the exercise. Therefore we took this into consideration and discussed this with some experts in the field. We even conducted our own studies to define a threshold for pseudoephedrine, because we don’t want to unnecessarily prohibit its intake This is a useful drug commonly sold over the counter for simple cold symptoms such as a stuffy or runny nose, and it seemed a bit extreme to consider a global ban. In the end, we had a pretty clear-cut decision, which has been published by WADA in the scientific literature. We believe that pseudoephedrine can be performance enhancing, but only at a certain dosage level. This is a strategy we propose and has been on the List for few years now and is pretty well accepted. This also demonstrates the role of the List Expert Group and the Health Medical and Research Committee in reviewing the scientific knowledge.

Sean: From a scientific perspective, these processes and regulations appear to be very technical and very detailed. They involve considered research and detailed discussion between experts.

How much of a challenge is it to explain the reasoning behind certain decisions and to make it accessible so that various stakeholders, including the athletes, so they can actually understand and comply with the Code? As you say, it is a very technical area; you [WADA] spend a year or more continuously reviewing this process. So how do you deal with this challenge?

Dr Rabin: Well your question is a good one because that is almost an impossible challenge, in a sense that you cannot satisfy everybody. Why? Because the list of Prohibited Substances and Methods is legal document. Why? Because when we end up in court and we prosecute some cases, someone will question the validity of substances or methods on the List, the wording of the List, why a substance is on the List – and we regularly face such questions. From a legal standpoint, the document has to be very carefully drafted. This is of course also a scientific and medical document. We have to be accurate in the way we name substances, the way they are described and the way we qualify some of the substances. This is a good part of the work of the List Expert Group. However, this is also an educational/communication document, but it has to be legally and scientifically accurate. We have to explain to athletes that a drug has to be written either with an accurate chemical name or described by chemical nomenclature because it has never been described before, or presented by an INN [International Nonproprietary Name] given by the WHO [World Health Organisation]. We understand the complexity, but given the importance of the document and for the need for accuracy, we cannot say simply, “it is a cholesterol based molecule”. This would mean that cholesterol and all endogenous steroids would be prohibited, which is not the essence of what we are trying to achieve. You have to try and find a balance between all these constraints, which by definition makes it a complex document to almost everybody; but we do our best to find a compromise that our stakeholders are happy with. We hear from athletes that the list is too complicated so we do try to simplify it. We talk to them and then understand why legally and scientifically you need to name such complicated substances, and explore with them see if there are any simpler alternatives.

Now the real challenge is when we are asked to take decisions on substances for which there is almost no scientific literature available. Thus, you have to extrapolate either from similar compounds or classes of similar substances; you need access to information that is not always available. In addition to when there is scarce scientific information available, the data may not always be directly applicable to healthy people. For example, if you have information on the effect of a drug on people with diseases, it does not necessarily mean you do have information of the effect of the drug on healthy people, and sometimes super healthy athletes who have an incredible and sometimes fairly unique physiology and lifestyle. We are not in a position, for ethical reasons of course, to conduct these kinds of studies with prohibited substances in elite athletes. So, more often than not, the challenge we face is how to make sure the information that is reviewed is sufficiently researched and accurate to be safely extrapolated to the population of interest to WADA, which is the athlete population. That is a main challenge. It is not always easy; sometimes we have to generate this information. We call upon experts in the field with their views and sometimes the latest information on science that is not necessarily published, to make sure that the most reasonable decision is taken.

Sean: I think that illustrates the challenge that you, WADA, and the rest of the stakeholders in the anti-doping movement, and the athletes that are trying to “compete clean”, as we say now, face on a day-to-day basis. Hopefully this gives some illustration into the thought processes, decisions, and rigorous review process that WADA go through. That is not to say that it is perfect. 

Sometimes there is an assumption that WADA make very quick reactive decisions. What would you say to in response to this?

Dr Rabin: No, on the contrary. Sometimes there are extensive discussions. It is human nature to be tempted to postpone and not to take a decision, and we are trying to make sure this is not what we are doing at WADA. One element I would like to insist upon (because this is also part of the problem) is the polarized opinion that we receive from some of our stakeholders. They can be 180 degrees apart. Sometimes, our stakeholders saying, “This substance has to be included in the list of prohibited substances.” Something you have to appreciate when one works for a world organization such as WADA is that science and medical practice is not homogeneous around the world, in particular medical practice. Some people hold opinions, based on cultural background, not always on universally accepted medical or scientific knowledge. Some cultural backgrounds do not have the same perception for drugs or the way they use drugs as others. This is why a drug is not necessarily available all over the world because a drug agency does not view them in the same way.. The judgment on science, therefore, is not always the same, the medical practice is not always the same, and based on this stakeholders tell you: “This drug, no way WADA, you should not allow this drug at all.” and others say, “This drug is perfectly acceptable. It can be purchased over the counter in my country.” I refer to pseudoephedrine to continue with this example. Pseudoephedrine is a drug available over the counter in many countries but not in others. So the perception of the risk of the drug is not necessarily the same, and the use of the drug is not necessarily the same in daily medical practice. That creates interesting situations where you’ve got stakeholders providing interesting and well-supported opinions based upon local practice, but in the end not applicable worldwide. It often feels as if you are in the middle making your own judgments.. In the end, you know that you are not going to satisfy everybody and you have to rely on expert judgment to make the most rational decision for the rules to apply globally. As long as we base our decisions on scientific and medical facts, taking into account the feedback of our stakeholders and testimonies from the field, then this is the best process we can implement. We need to be very factual, have good and strong reasoning, and where needed have some criteria to judge on the relevance of the information we have. For example, would not give the same weight to an article in Nature or Science, compared to an article published online with no peer-reviewed process; so again you have to weigh evidences that are provided to you and make your judgment.

Sean: I think you have done a very good job at explaining the difficulty involved in the process of selecting what research to take into account. I’m sure that lots of people will be sympathetic with the challenges you face.

I hope this interview goes some way into shedding some light on that process that is undertaken to review the List and the work of WADA. Hopefully it would be great if more athletes can get engaged in the process. I know there is an Athlete Committee at WADA and that UK Anti-Doping and United States Anti-Doping Agency are a couple of anti-doping agencies who are trying to engage athletes in that process. One hopes the more athletes that are involved in that process, they better counterbalance they can provide and help to keep the language in the List as simplified as possible.

Dr Rabin: We hear from athletes, we are very sympathetic to their requests and we discuss these with them. Regularly, when I present the list at the WADA Executive Committee, the athletes approach us and say: “what about this, this is difficult for us to understand”, and we then offer further explanations. We don’t do it for the sake of writing beautiful names or chemical names, we do it because we have no alternative. I would prefer to describe the molecule by the name that everyone is using, for example Paracetamol, rather than having to use a long and complicated chemical name. I know that unless you are a chemist or an individual with a good chemical background, you will be unable to visualize this and see what it means. But the reality is that not all the drugs we face in anti-doping are legal drugs, some are illegal. Some are designer drugs that have never been approved for human use. When we are still facing those substances, we have to name them because otherwise the legal system will say: “sorry how can you be expect this drug to be considered prohibited if it is not on the list?” But you cannot assume that with no particular chemical and pharmacological background that everyone will understand what you mean. So we do listen to the comments.

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