Table 2 Key insights from the qualitative research on future N-of-1 therapeutic equivalence tests on local generic drugs

Regulatory authority members did not support the need for testing local drugs

This is a key uncertainty that should addressed prior to the planned test. It demonstrates the need for creating a deep understanding by relevant authorities of the relevance of testing local drugs and its implications to improve clinical care through continuous education and discussion.

IRB members were concerned about the potential unintended consequences of providing local drugs to unstable patients

(1) Designing strict eligibility criteria to include stable patients only/patients whose condition is controlled is important

(2) Strict and regular patient follow up is required

(3) Data safety monitoring board need to be established

Develop clarity of the approval process

Regulatory authority wanted application through the normal channels. That is, if the IRB indicated that regulatory authority was deemed necessary, then approval from the authority would be sought. If not thought necessary, the authority would not be approached.

Trial design, conduct and processes

Issues related to N-of-1 test

Regulatory authority members did not accept the test in principle

The need for further work to increase awareness of the potential role of N-of-1 tests in supporting the regulatory quality assurance system and improving clinical care

A potential negative impact on the health care system if local drugs (which are cost effective) turn out to be less effective

This is a major issue. Local drugs represent an affordable option in usual care. The findings of the proposed tests may require a change from usual practice.

Further work, including meetings and workshops that enhance understanding and benefits of the study (with the inclusion of other parties they trust), could be a possible solution. This work should emphasize (1) Short term and long term negative consequences of using medicines that are not proven to work (2) the contribution of N-of-1 tests to patient care and advancement of the health care system (3) designing strategies that can anticipate and respond to findings of the proposed N-of-1 tests are imperative, eg. a system regarding who should pay if local drugs do not work on an individual patient and the patient cannot afford alternative drugs. Also dialoguing with medicine manufacturers on the benefits of identifying the cause of the problem(s) and correcting it.

Recruitment and retention

Doctors are too busy and lack research skill to recruit and make follow up patient assessments.

Due to high patient load and lack of research culture in hospitals, establishing an N-of-1 testing service in universities and research facilities could be a pragmatic solution. Then, provide an N-of-1 test service to the hospitals through a patient referral-feedback model, a service that clinicians are used to (referral from hospital, test, and report back to the hospital).

Most patients are poor, so cannot afford trial related costs

Financing of N-of-1 tests deserves attention as patients alone cannot afford additional costs of these tests. Apart from the government and patient-centred care advocators, insurance and local pharmaceutical companies should be involved in this matter

Patients are busy in their daily life

Limit patient follow up and use health technologies as much as possible in the proposed test

Most patients are illiterate -they can’t read, or understand and record on trial documents

Recruit only patients who are literate or have a literate assistant for the duration of the study.

Ethical and regulatory issues

Mixed views on ethical requirements

The IRB members believe that N-of-1 tests on local drugs (which are already approved) is part of quality assurance, and hence IRB approval suffices. Whereas key informants of the regulatory authority emphasised the need for regulatory approval so as to monitor potential unanticipated negative consequences of the proposed test. Posing these regulatory requirements negatively affects the feasibility of using N-of-1 tests in daily clinical care.

These issues can be addressed by (1) including education of patients and doctors regarding interpretation and scope of individual N-of-1 study results in the proposed study as a possible option to reduce/avoid the risk of biased negative perceptions about local drugs (2) As mentioned above, meetings and workshops involving members of both IRB and regulatory authority are needed to address the tension of mixed views regarding ethical requirements and to develop a mutual guideline regarding the level of endorsement required for future N-of-1 tests on local drugs.

Develop clarity of the approval process

The regulatory authority stated that they would only be involved in applications presented through the normal channels. That is, if the IRB indicated that regulatory authority was deemed necessary, then approval from the authority would be sought. If the IRB did not think it was necessary, the authority would not be approached.