Medicines (Clinical Trials) (Amendment) Regulations 1998

No. S 250

Medicines Act

(Chapter 176)

Medicines (Clinical Trials) (Amendment)
Regulations 1998

In exercise of the powers conferred by sections 18 and 74 of the Medicines Act, the Minister for Health hereby makes the following Regulations:

Citation and commencement

1. These Regulations may be cited as the Medicines (Clinical Trials) (Amendment) Regulations 1998 and shall come into operation on 1st August 1998.

Amendment of regulation 2

2. Regulation 2 of the Medicines (Clinical Trials) Regulations (Rg 3) (referred to in these Regulations as the principal Regulations) is amended —

(a)

by deleting the definition of “director”;

(b)

by inserting, immediately after the definition of “holder of a certificate”, the following definitions:

“ “legal representative”, in relation to a person who is to be used as a subject in a clinical trial, means an individual or judicial or other body authorised under the law to consent on behalf of that person to his participation in the clinical trial;

“principal investigator” means a doctor or dentist, as the case may be, specified in a certificate as the person responsible for the conduct and supervision of a clinical trial;

“sponsor” means an individual, company, institution or organisation which takes responsibility for the initiation, management or financing of a clinical trial;”; and

(c)

by deleting the full-stop at the end of the definition of “test material” and substituting a semi-colon and, by inserting immediately thereafter the following definition:

“ “window period” means the period, determined based on scientific evidence, within which the test material must be administered to a subject on a clinical trial for it to have the intended potential direct benefit to the subject.”.

Amendment of regulation 5

3. Regulation 5(3) of the principal Regulations is amended by inserting, immediately after the word “impose”, the words “, including any condition requiring the sponsor of a clinical trial to obtain and maintain insurance to provide compensation in the event of injury or loss arising from the conduct of the clinical trial on such terms as the licensing authority may approve”.

Amendment of regulation 7

4. Regulation 7 of the principal Regulations is amended —

(a)	by deleting the word “director” and substituting the words “principal investigator”; and
(b)	by deleting the word “Director” in the marginal note and substituting the words “Principal investigator”.

Amendment of regulation 10

5. The principal Regulations are amended by deleting the word “director” wherever it appears in regulation 10 and in the marignal note and substituting in each case the words “principal investigator”.

Deletion and substitution of regulation 11, and new regulation 11A

6. Regulation 11 of the principal Regulations is deleted and the following regulations substituted therefor:

“Consent required to use person as subject in clinical trial

11.—(1) Subject to paragraphs (2) and (3), a holder of a certificate shall not use a person as a subject in a clinical trial unless the following conditions are satisfied:

(a)

in the case of a person of or above the age of 21 years, or a person below the age of 21 years who is married, except with the consent of that person;

(b)

in the case of a person below the age of 21 years who is not married, except with the consent of that person and —

(i)	that person’s parent or guardian (if there is no parent); and
(ii)	if different from sub-paragraph (i), that person’s legal representative.

(2) The consent of a person below the age of 21 years who is not married shall not be required under paragraph (1) if —

(a)	that person lacks sufficient understanding to give such consent; and
(b)	there is a reasonable prospect that participation in the clinical trial will directly benefit that person.

(3) The consent of a person who is unconscious or incapable of exercising rational judgment shall not be required under paragraph (1) if —

(a)

the principal investigator and a doctor who is not otherwise participating in the clinical trial certify in writing that —

(i)	that person is unconscious or incapable of exercising rational judgment; and
(ii)	it is not likely that that person will regain consciousness and be capable of exercising rational judgment within the window period;

(b)

consent thereto has been obtained from —

(i)	that person’s spouse, parent, guardian (if there is no parent) or any other person having charge of him; and
(ii)	if different from sub-paragraph (i), that person’s legal representative; and

(c)

there is a reasonable prospect that participation in the clinical trial will directly benefit that person.

(4) Subject to paragraph (5), consents obtained for the purposes of these Regulations shall be —

(a)	in written form approved by the licensing authority and signed and dated by the person giving his consent; or
(b)	if the person giving his consent is unable to sign the written form, in any other form and manner as the licensing authority may approve.

(5) If the person giving his consent for the purposes of these Regulations is unable to read, the consent form referred to in paragraph (4) shall be read and explained to him in the presence of an impartial witness who shall sign and date the consent form to attest that the form was accurately explained to that person and that his consent thereto was freely given.

(6) Any person making a decision for the purposes of paragraph (1)(b)(i) or (ii) or paragraph (3)(b)(i) or (ii) or regulation 11A(8) shall act in the best interests of the person to be used as a subject in the clinical trial and have regard, so far as ascertainable, to the subject’s past and present wishes and feelings and any factors which the subject would consider if he were able to do so.

(7) Paragraphs (2) and (3) and regulation 11A shall not apply if the clinical trial can practicably be carried out using only subjects who have given their own consent under paragraph (1).

(8) Paragraphs (2) and (3) and regulation 11A shall operate subject to any advance medical directive made under the Advance Medical Directive Act (Cap. 4A).

(9) For the purposes of paragraphs (2)(b) and (3)(c), a clinical trial shall not be taken to hold out any reasonable prospect of direct benefit to the subject unless —

(a)	appropriate animal and other pre-clinical studies have been conducted, and the information derived from those studies and related evidence support the potential for the proposed use of the test material to provide a direct benefit to the subject; and
(b)	risks associated with the clinical trial are reasonable in relation to what is known about the medical condition of the subject, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed use of the test material.

Clinical trials in emergency situations

11A.—(1) No person shall conduct a clinical trial under this regulation except with the prior approval of the licensing authority given under paragraph (2).

(2) The licensing authority shall not give its approval for any clinical trial to be conducted under this regulation unless the principal investigator and 2 specialists who are not otherwise participating in the clinical trial certify in writing that —

(a)

the clinical trial needs to be conducted on subjects who are in a life-threatening situation to determine the safety and effectiveness of the test material;

(b)

available treatments are unproven or unsatisfactory;

(c)

there is a reasonable prospect that participation in the clinical trial will directly benefit the subjects because —

(i)	the subjects are facing a life-threatening situation that necessitates intervention;
(ii)	appropriate animal and other pre-clinical studies have been conducted, and the information derived from those studies and related evidence support the potential for the proposed use of the test material to provide a direct benefit to the individual subjects; and
(iii)	risks associated with the clinical trial are reasonable in relation to what is known about the medical condition of the potential class of subjects, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed use of the test material;

(d)

the subjects will not be able to give their consent as a result of their medical condition;

(e)

it is not feasible to request consent from the subjects or their legal representatives within the window period;

(f)

there is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the clinical trial; and

(g)

the clinical trial could not practicably be carried out if the consents referred to in regulation 11 must be obtained.

(3) Where the licensing authority has given its approval under paragraph (2) for the clinical trial to be carried out in accordance with this regulation, the consents referred to in regulation 11 need not be obtained before using any person as a subject in the clinical trial if the principal investigator and 2 specialists who are not otherwise participating in the clinical trial certify in writing before using that person as a subject in the clinical trial that —

(a)	that person is facing a life-threatening situation which necessitates intervention;
(b)	that person is unable to give his consent as a result of his medical condition;
(c)	it is not feasible to request consent from that person or to contact his legal representative within the window period; and
(d)	neither that person nor his legal representative nor any member of that person’s family has informed the principal investigator of his objection to that person being used as a subject in the clinical trial.

(4) The holder of a certificate shall, within 7 working days of making any certification in accordance with paragraph (3), submit a copy of that certification to the licensing authority in such form and manner as the licensing authority may require.

(5) If a person is or is about to be used as a subject in a clinical trial under this regulation, the holder of a certificate shall, at the earliest feasible opportunity —

(a)	give to that person a full and reasonable explanation of the matters referred to in regulation 13; and
(b)	request the consent of that person to be used or to continue to be used as a subject in the clinical trial.

(6) If the person to be used as a subject in the clinical trial is unable to give his consent thereto because of his medical condition, the holder of a certificate shall, at the earliest feasible opportunity —

(a)	make all reasonable efforts to contact the legal representative of the person to be used as a subject in the clinical trial;
(b)	give the legal representative a full and reasonable explanation of the matters referred to in regulation 13(1); and
(c)	request the legal representative’s consent for that person to be used or to continue to be used as a subject in the clinical trial.

(7) If the person to be used as a subject in the clinical trial is unable to give his consent thereto because of his medical condition and it is unlikely that his legal representative can be contacted within the window period, the holder of a certificate shall, at the earliest feasible opportunity —

(a)	make all reasonable efforts to contact any member of that person’s family; and
(b)	give the member of that person’s family a full and reasonable explanation of the matters referred to in regulation 13(1).

(8) If, at any time before or after a person has commenced to be used as a subject of a clinical trial under this regulation —

(a)	that person or his legal representative refuses to give his consent referred to in paragraph (5) or (6), as the case may be; or
(b)	where neither the consent of that person nor his legal representative has been obtained, any member of his family, informs the holder of a certificate that he objects to that person being used as a subject in the clinical trial,

the holder of a certificate shall refrain from using or cease to use, as the case may be, that person as a subject in the clinical trial.

(9) For the purposes of this regulation, “specialist” means a doctor whom the licensing authority is satisfied is an expert in the medical condition of the subject which is being treated.”.

Deletion and substitution of regulation 13

7. Regulation 13 of the principal Regulations is deleted and the following regulation substituted therefor:

“Duty to give full explanation and information

13.—(1) Before a clinical trial is carried out or conducted, the holder of a certificate shall give the subject and any person giving consent on behalf of the subject, a full and reasonable explanation of the following:

(a)	that the clinical trial involves research;
(b)	the purpose of the clinical trial;
(c)	the treatments to be administered in the clinical trial and the probability for random assignment of each treatment;
(d)	the procedures to be followed in the clinical trial, including all invasive procedures;
(e)	the responsibilities of the subject;
(f)	the aspects of the clinical trial which are experimental;
(g)	the reasonably foreseeable risks or inconveniences to the subject and, where applicable, to any embryo, foetus or nursing infant;
(h)	the reasonably expected benefits, including whether there is any intended clinical benefit to the subject;
(i)	any alternative procedures or treatments available to the subject, and their potential benefits and risks;
(j)	any compensation and treatment available to the subject in the event of injury arising from participation in the clinical trial;
(k)	any prorated payment to the subject for participating in the clinical trial;
(l)	any anticipated expenses to the subject from participating in the clinical trial;
(m)	that the subject’s participation in the clinical trial is voluntary and that he may refuse to participate in or may withdraw from the clinical trial at any time without penalty or loss of benefits which the subject would otherwise be entitled;
(n)	the persons who will be granted access to the subject’s medical records and the extent of such access, including the possibility that the licensing authority may inspect the records;
(o)	the extent to which records identifying the subject will be kept confidential;
(p)	that the subject or his legal representative will be informed in a timely manner of any information becoming available which may be relevant to the subject’s willingness to continue participating in the clinical trial;
(q)	the persons to contact for further information relating to the clinical trial and the rights of subjects and in the event of injury arising from participation in the clinical trial;
(r)	any foreseeable circumstances under or reasons for which the subject’s participation may be terminated;
(s)	the expected duration of the subject’s participation in the clinical trial;
(t)	the approximate number of subjects involved in the clinical trial; and
(u)	any other information which the licensing authority may require to be given.

(2) If any information becomes available which may be relevant to a subject’s willingness to continue participating in a clinical trial, the holder of a certificate shall, at the earliest feasible opportunity, give to the subject or his legal representative a full and reasonable explanation of that information.

(3) If a person referred to in regulation 11(2) or (3) is used as a subject in a clinical trial and subsequently becomes capable of giving his own consent, the holder of a certificate shall, at the earliest feasible opportunity, give to that person a full and reasonable explanation of the matters referred to in paragraph (1) and request his consent to continue to be used as a subject in the clinical trial.

(4) If a subject in a clinical trial refuses to give his consent referred to in paragraph (3), the holder of a certificate shall cease to use that person as a subject in the clinical trial.”.

Deletion and substitution of regulation 16

8. Regulation 16 of the principal Regulations is deleted and the following regulation substituted therefor:

“Notification of serious adverse events

16.—(1) The holder of a certificate shall, as soon as practicable, notify the licensing authority in writing of any serious adverse event which is likely to affect the safety or well-being of the subject which has arisen during the clinical trial or which has come to his knowledge from reports of similar clinical trials conducted elsewhere.

(2) For the purposes of this regulation, “serious adverse event” means any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not caused by the use of the test material, which —

(a)	results in death;
(b)	is life-threatening;
(c)	requires in-patient hospitalisation or prolongation of existing hospitalisation;
(d)	results in persistent or significant disability or incapacity; or
(e)	causes any congenital anomaly or birth defect.”.

Amendment of regulation 18

9. Regulation 18 of the principal Regulations is amended —

(a)

by deleting sub-paragraph (c) of paragraph (2) and substituting the following sub-paragraph:

“(c)

kept at least for whichever of the following periods expires later:

(i)	until there are no pending or contemplated marketing applications of the test material in Singapore;
(ii)	2 years after the last approval of a marketing application for the test material in Singapore;
(iii)	where the clinical trial is discontinued, 2 years after the licensing authority has been informed of the discontinuation of the clinical trial under regulation 9;
(iv)	6 years after the completion of the clinical trial; or
(v)	such other period as the licensing authority may direct.”; and

(b)

by inserting, immediately after paragraph (3), the following paragraph:

“(4) In this regulation, “marketing application” means an application for a product licence under the Act in respect of the test material.”.

New regulation 19A

10. The principal Regulations are amended by inserting, immediately after regulation 19, the following regulation:

“Duty to comply with guidelines and instructions of licensing authority

19A. Every sponsor, principal investigator or holder of a certificate shall comply with any guidelines or instructions relating to the conduct of clinical trials issued by the licensing authority and notified to such sponsor, principal investigator or holder of a certificate, including the Singapore Guideline for Good Clinical Practice.”.

Amendment of regulation 20

11. Regulation 20 of the principal Regulations is amended by deleting the words “regulation 5(1) or regulations 7 to 19” and substituting the words “regulation 5(1), 7, 8, 9, 10, 11(1), 11A(5) to (8), 12, 13, 14(1), 15, 16, 17, 18, 19 or 19A”.

Made this 3rd day of April 1998.

KOH YONG GUAN

Permanent Secretary,
Ministry of Health,
Singapore.

[PD(NDU) 11:01/1; AG/LEG/SL/176/97/2 Vol. 1]

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