Table 5 Examples of ICP elements – risks and benefits

 Please avoid using the statement “Do not worry about the amount of blood taken, because it is very small” (Page 4/6). In fact, 2 mL will be taken per visit, which is not a very small amount. Also, state the blood volume in teaspoon(s)/tablespoon(s) in the summary table for blood collection.

X

X

X

 In the risk section of the Participant Information Sheet, please amend the text to read: “Some questions may make you feel uneasy or uncomfortable. You may refuse to answer any question at any time.”

X

X

 In the risk section of the Participant Information Sheet, the researcher should state that chloroquine (CQ) alone is not a standard treatment, and that if the patient is randomized to this group, the risk of relapse may increase.

X

X

X

 In the risk & discomfort section of the Participant Information Sheet, the researcher should mention that, in addition to bruising, there may be a risk of becoming infected, and if infection occurs, how the research team plans to handle it.

 Please state clearly that there may be a risk of a hemolysis event for any volunteer with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), and how such an event would be identified; this is important for enabling potential study volunteers to make an informed decision on participating in the study.

X

X

X

 The researcher should reword the phrase “thus there is no risk” to “the risk of mosquito bite is minimal; however, if you are bitten by a mosquito and are infected with malaria, the researcher will….” Explain what the researcher will do and who will be responsible for the costs.

X

X

X

 On Page 2 of 10 of the Participant Information Sheet (English version), it is stated that “We still want to check to see that there are no unexpected side-effects from XXX treatment”; this statement is not quite correct. The purpose of the study is to test dose deceleration; therefore, patients should be informed of any associated risk. This should include, for example, that treatment XXX is not the current standard treatment and that patients may run the risk of not being cured or deteriorating.

X

X

X

 Please add a statement that research participants may suffer hemolysis or anemia, and may receive a placebo.

X

X

 In the statement addressing potential risk and discomfort, “If there is any side effect ... the researcher will provide treatment and care immediately”, please change to “… should a side effect occur, the researcher will be responsible for treatment and care. You will not have to pay for any cost related to the event”.

X

X

X

 Please specify the risk(s) of all medications used in the study, and present them clearly in both the research proposal and the Participant Information Sheet.

X

X

X

 In the risk and benefit section, it should not be stated that “All study procedures are routine and pose no additional risk to the study participant”, because these extra investigations are not routine procedures.

X

X

 In the description of the study procedure: is venipuncture necessary, since after admission the researcher will only need a specimen for blood film and filter paper, which could be obtained from a finger prick?

X

 The Participant Information Sheet should include details of what the patient should do if he/she gets re-infected after discharge from hospital.

X

X

 Please specify what will be done should there be a serious adverse event.

X

X

 In the event that disease is detected, specify the list of diseases for which the PI will provide free treatment/intervention. Also include the management of the intervention and list the diseases for which the PI will transfer the patient to a suitable hospital.

X

X

X

 Please revise the statement “No risks or discomforts are anticipated from taking part in the study”. Participants will require a long time to answer the questionnaire used in this study. Please inform the study participants about time requirements and their rights in voluntarily answering any sensitive questions in the questionnaire. Particularly for the focus group and in-depth interview, please mention that participants have the right to withdraw or not answer any questions.

X

X

X

 In the Participant Information Sheet, it is stated that about 10 drops (500 μl) of blood would be collected for the current study, with blood for future use. Does that mean the researcher plans to draw more blood than is actually needed for the current study? In addition, for volunteers aged >13 years, why does the researcher need another 5 ml, when the 10 drops (500 μl) should be enough. Please reconsider the amount of blood required for this study.

X

X

X

 The risk-benefits of the study outlined in the protocol should include clear information on the provision of treatment/intervention/medical care to children when abnormalities are detected.

X

X

 Please explain co-morbidity and potential side effects, since the local people may not understand what the researcher is talking about.

X

X

 Page 11/24: Treatment for recurrent Plasmodium vivax (PV) infection will be the same as open-label study drug(s). If infections recur, it might suggest that the drugs taken previously were not appropriate; therefore, a standard drug regimen should be used instead to treat a recurrent episode. Why do you not want to use the standard regimen to treat patients with recurrent PV?

X

X

 If participants show symptom(s) of clinical hemolysis, please specify clearly how you will treat the symptom(s).

X

X

X

 Please specify the alternative (standard) treatment, mentioned on page 1 of the Informed Consent Form.

X

X

X

 Please add a benefit section to the Participant Information Sheet, describing the potential benefits for the study volunteers and/or others, such as “… you or your child might not receive any direct benefit from participating in this study, but the results of the study could be used for …”

X

X

X

 What are the potential benefits of this study to others? Please describe.

X

X

 A “small sum of money” is not a benefit to the patient; it is rather compensation and a token of appreciation. Please delete from the benefit section.

X

 In the description of direct benefit, please change the sentence, “You will receive second-line treatment” to “You will be referred/sent to a malaria clinic or hospital for treatment.”

X

X

 In the benefit section of the Participant Information Sheet, the researcher should delete “You will not get vivax malaria again unless you get infected from a mosquito bite”. Based on the content flow in this part, the sentence might better be “You will still receive primaquine, even though you are not participating in this study”

X

X