There are lots of articles and blogs (including this one) which discuss what to do and how to handle situations, issues and procedures. There are very few though which discuss things not to do. We’ll tackle that now.
There are lots of things to avoid doing and lots of things which you could do but with great risk and which should generally be avoided. Problems and chastisement can come from the company (quality, management, legal, colleagues and others), from the FDA or other health agencies, from social media, the press and from investigators, patients and health care professionals.
Causality
Be very careful in questioning causality assessments from investigators, patients and others in the company. If you are the professional assigned to make causality assessments by the written SOP, then you should make them. They may be questioned by others and, again per SOP, this should be handled as described in the policy to iron out any differences that might occur.
A not uncommon situation is in a clinical trial where the investigator makes a causality call on a serious adverse event (SAE) and the company disagrees. For example, the investigator says the SAE is related or probably related to the study drug and someone in the company (maybe you, maybe someone else) disagrees. It may be suggested to call the investigator and “explain why it is unrelated” or “tell him to change his assessment” or some similar request or demand. It may often come from one’s boss or, worse, someone in the company in a position of power who does not understand how the SAE causality systems operate (both at FDA and elsewhere). It is very hard to disobey a direct order to contact the investigator.
The best way to handle this is to explain to the “demander” that the company cannot force a change by the investigator (even though we are paying him/her to do the study) but that we certainly can discuss the situation, explain why it may not be related and discuss the issues with him/her. We cannot force the investigator to change it. Then one should call the investigator (sometimes an MD to MD call works best) and discuss in a very polite and scientific way the issues as the company sees them.
One should not press for a change even if his/her opinion makes the case into a reportable SUSAR which the company feels is incorrect. Of course, do not browbeat, threaten or be aggressive with the investigator or his/her staff. This can lead to real problems if the investigator is offended or feels he or she has been attacked and threatened by the company. At worst, he or she could contact the FDA or have the investigator’s attorney contact the company. This could also go public on social media.
Real problems can also occur if the internal demander is unreasonable, doesn’t understand the system and threatens or punishes you. This is why the business of drug safety and PV can be very tricky and difficult. Most serious companies understand what they can and can’t do. If they overstep the line, the drug safety officer should explain politely and have internal allies (e.g. regulatory and legal) assist in educating the demander. If that fails, it may be time to get your CV up to date and move on.
Similarly, one should not confront or try to have changes made in judgment calls in the post-marketing setting. Patients, pharmacists, physicians and others may have a particular opinion that is at odds with the company’s view. One may discuss and educate but if the person doesn’t change his or her opinion you have to live with what they say. The same is true for seriousness and “medically important”. The reporter may say the case is serious and/or medically important. You may disagree and certainly can discuss it but the reporter’s opinion must be used if he or she doesn’t change it.
Legal Cases
Often adverse events or bad outcomes that the plaintiff considers due to the drug or the company’s fault will produce law suits against the company. These suits may involve records in the drug safety, PV, signaling and other departments or processes done in these departments. There may be requests by the legal department and by the plaintiff for records from these departments for “discovery”.
Obviously, SAE case records, aggregate reports and other documents must be supplied. The DS and other departments must work closely with the Legal Department (and outside lawyers if involved). This will often be very time-consuming and frustrating for the drug safety personnel. They will be taken away from their regular work and have to pull and go through records, give depositions, sit in meetings etc. You cannot say no to this. You must cooperate. Usually the company attorneys are sympathetic to the situation and will try to work around your drug safety schedule but they have their job to do and you will have to supply them with what they need.
So, do not refuse requests from legal. You can negotiate and explain why you think something is not appropriate or should not be supplied. But ultimately the lawyers need to get what they need.
Legal may “freeze” your records on some cases or patients. This means you cannot alter, change, update, delete etc. any files or records. In some cases you may even be forbidden to access them. Any contacts or correspondence with outside attorneys, patients, doctors, investigators or others should not be done directly by drug safety. Any such communication or request should be turned over to legal who will usually do the follow up. Similarly, if you need to get follow up on cases from physicians, pharmacists, patients etc. you cannot (usually) do it directly but rather the request is sent to legal who forwards it on. This will produce delays and that can be problematic for expedited cases. Let legal know that you have regulatory requirements and plan your FDA and other health agency submissions accordingly. Submissions may be less than complete but there is nothing that can be done about this.
Do not cheat. Do not touch the files. Do not change anything. Do not change dates or falsely date notes or changes.
Audits and Inspections
This one you should know already. Do not ever lie to an inspector or auditor (or anyone else for that matter).
Do not lie on any documents submitted to health authorities.
Email and Documentation
Do not get into email wars. Do not insult or call people names in emails or other documents. These can come back to haunt you at a later date or in court. Most of these documents are “discoverable” which means that in lawsuits they may be submitted to the plaintiffs attorneys and can be used in court. Try to avoid “return all” in emails. An email going to the wrong person can be disastrous. Emails usually cannot be recalled and once they are sent you do not know to whom they will be forwarded.
Say The Same Thing to All Health Agencies At the Same Time
Do not say different things to different health agencies. Sometimes it is not possible to say the same thing to different health agencies however. This is true in SUSAR submissions to the EMA and FDA. The FDA requires that the causality be determined by the company. Even if the investigator feels that the case is related to the drug, the company may overrule this and not submit the case to FDA as an expedited SUSAR. The EMA requires submission if either the investigator or the company (or both) say the case is related. Thus the EMA will be informed and the FDA not. This is not avoidable. In other instances though, particularly with issues that are urgent and represent possible significant risk to patients, say the same thing to all agencies at the same time. The author recalls a case years ago where an expedited 15 day report went to FDA on day 8 and to the EMA on day 14. The FDA acted immediately and publically even before the EMA had been informed. Although all the requirements were handled correctly and the 15 day clock was met, the company was severely chastised by the French health agency for not informing them when we informed the FDA.
This is not a complete list. There are lots of other no-no’s some of which are particular to drug safety and some true in life in general. Be careful, very very careful.
