How experiences become data: the process of eliciting adverse event, medical history and concomitant medication reports in antimalarial and antiretroviral interaction trials.
BACKGROUND
Accurately characterizing a drug's safety profile is essential. Trial harm and tolerability assessments rely, in part, on participants' reports of medical histories, adverse events (AEs), and concomitant medications. Optimal methods for questioning participants are unclear, but different methods giving different results can undermine meta-analyses. This study compared methods for eliciting such data and explored reasons for dissimilar participant responses.


METHODS
Participants from open-label antimalarial and antiretroviral interaction trials in two distinct sites (South Africa, n = 18 [all HIV positive]; Tanzania, n = 80 [86% HIV positive]) were asked about ill health and treatment use by sequential use of (1) general enquiries without reference to particular conditions, body systems or treatments, (2) checklists of potential health issues and treatments, (3) in-depth interviews. Participants' experiences of illness and treatment and their reporting behaviour were explored qualitatively, as were trial clinicians' experiences with obtaining participant reports. Outcomes were the number and nature of data by questioning method, themes from qualitative analyses and a theoretical interpretation of participants' experiences.


RESULTS
There was an overall cumulative increase in the number of reports from general enquiry through checklists to in-depth interview; in South Africa, an additional 12 medical histories, 21 AEs and 27 medications; in Tanzania an additional 260 medical histories, 1 AE and 11 medications. Checklists and interviews facilitated recognition of health issues and treatments, and consideration of what to report. Information was sometimes not reported because participants forgot, it was considered irrelevant or insignificant, or they feared reporting. Some medicine names were not known and answers to questions were considered inferior to blood tests for detecting ill health. South African inpatient volunteers exhibited a "trial citizenship", working to achieve researchers' goals, while Tanzanian outpatients sometimes deferred responsibility for identifying items to report to trial clinicians.


CONCLUSIONS
Questioning methods and trial contexts influence the detection of adverse events, medical histories and concomitant medications. There should be further methodological work to investigate these influences and find appropriate questioning methods.
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa. elizabeth.allen@uct.ac.za.
Elizabeth N
EN
Allen
Adiel K
AK
Mushi
Isolide S
IS
Massawe
Lasse S
LS
Vestergaard
Martha
M
Lemnge
Sarah G
SG
Staedke
Ushma
U
Mehta
Karen I
KI
Barnes
Clare I R
CI
Chandler
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D004347:Drug Interactions; D004983:Ethanolamines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000009:adverse effects* / Q000627:therapeutic use; D017144:Focus Groups; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007407:Interviews as Topic; D008288:Malaria / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D057566:Self Report; D013019:South Africa; D013636:Tanzania; D016896:Treatment Outcome; D014342:Truth Disclosure
D019380:Anti-HIV Agents; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes