Appendix 11. Compassionate use

11.1 Definitions

The term “compassionate use” refers to the use of potentially life-saving experimental treatments to patients suffering from a disease for which no satisfactory authorised therapy exists and/or who cannot enter a clinical trial. For many patients, these treatments represent their last hope.
Experimental treatment is below referred to as investigational new drug (IND).

11.2 Indications

Both MDR-TB and XDR-TB can be life-threatening diseases for which approved drugs alone may be ineffective. In some cases, experimental TB drugs, used in combination with approved drugs, could potentially be effective or life-saving.

Compassionate use may be considered for patients presenting with a life-threatening condition (e.g. deteriorating clinical condition due to TB and/or severe immune depression) when:
– Available treatments have failed or are very likely to fail (e.g. regimen comprises less than 3 highly likely effective drugs and/or clinical evolution shows that the treatment is not effective).
– No medical or surgical options are appropriate.
– At least one highly likely effective drug is available (based in the DST result and previous use by the patient). The IND should never be used in monotherapy. It should always be used in conjunction with other drug(s) with proven or probable efficacy in order to prevent emergence of resistance to the IND. In that respect, will be taken into consideration on a case by case basis:
• the number of remaining drug(s) and their bactericidal or bacteriostatic activity: at least one bactericidal or 2 bacteriostatic drugs could be considered as a minimum;
• the reliability of the DST to the remaining drug(s), treatment history prior to the last DST result;
• the vulnerability to resistance amplification of the IND if known;
• the use of the IND does not result in the discontinuation of an essential effective drug. Special attention will be paid if the use of the IND imposes the replacement of an anti- TB drug by a less effective one.

Compassionate use might be considered for a single patient or a group of patients presenting similar characteristics.

The use of two INDs would basically follow the same indications and conditions. Possible interactions and overlapping toxicity between the INDs have to be taken into consideration.

11.3 Minimal requirements

Compassionate use should only be considered if conditions for an adequate management of DR-TB patients are in place: optimal treatment regimen; clinical, biological and bacteriological monitoring; adherence support and follow-up. Results of DST by a validated laboratory are critical to decision making.

In addition to the basic components of regular DR-TB case management a specific monitoring might be required for the use of an IND.

It is essential that a reporting system is in place in order to diligently report any adverse events.

11.4 National regulations

In most countries, only drugs for which a marketing authorization has been granted by the national regulatory agency can be used in humans. Some national regulatory agencies have developed mechanisms to facilitate the access to new drugs at different stages of development, but before market approval. In this case, a party can apply for approval of an IND and then seek the proper permission to import the drug to a country. The use of an IND requires permission from the proper national regulatory authorities and/or country ethic boards.